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Mixed Origins: HIV gp120-Specific Memory Develops from Pre-Existing Memory and Naive B Cells Following Vaccination in Humans.
AIDS research and human retroviruses (2023)
Basu M, Fucile C, Piepenbrink MS, Bunce CA, Man LX, Liesveld J, Rosenberg AF, Keefer MC, Kobie JJ.
Mixed Origins: HIV gp120-Specific Memory Develops from Pre-Existing Memory and Naive B Cells Following Vaccination in Humans.
AIDS Res Hum Retroviruses.
2023 Mar 22;
:.
Abstract: The most potent and broad HIV envelope (Env)-specific antibodies often when reverted to their inferred germline versions representing the naive B cell receptor, fail to bind Env, suggesting that the initial responding B cell population not only exclusively comprises a naive population, but also a pre-existing cross-reactive antigen-experienced B cell pool that expands following Env exposure. Previously we isolated gp120-reactive monoclonal antibodies (mAbs) from participants in HVTN 105, an HIV vaccine trial. Using deep sequencing, focused on immunoglobulin G (IgG), IgA, and IgM, VH-lineage tracking, we identified four of these mAb lineages in pre-immune peripheral blood. We also looked through the ∼7 month postvaccination bone marrow, and interestingly, several of these lineages that were found in prevaccination blood were still persistent in the postvaccination bone marrow, including the CD138+ long-lived plasma cell compartment. The majority of the pre-immune lineage members included IgM, however, IgG and IgA members were also prevalent and exhibited somatic hypermutation. These results suggest that vaccine-induced gp120-specific antibody lineages originate from both naive and cross-reactive memory B cells. ClinicalTrials.gov NCT02207920.
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A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine.
Science translational medicine (2022)
Chang LA, Phung E, Crank MC, Morabito KM, Villafana T, Dubovsky F, Falloon J, Esser MT, Lin BC, Chen GL, Graham BS, Ruckwardt TJ.
A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine.
Sci Transl Med.
2022 Dec 21;
14(676):eade0424.
Abstract: There is currently no licensed vaccine for respiratory syncytial virus (RSV). Here, we assess the effect of RSV fusion protein (F) conformation on B cell responses in a post hoc comparison of samples from the DS-Cav1 [prefusion (pre-F)] and MEDI7510 [postfusion (post-F)] vaccine clinical trials. We compared the magnitude and quality of the serological and B cell responses across time points and vaccines. We measured RSV A and B neutralization, F-binding immunoglobulin G titers, and competition assays at week 0 (before vaccination) and week 4 (after vaccination) to evaluate antibody specificity and potency. To compare B cell specificity and activation, we used pre-F and post-F probes in tandem with a 17-color immunophenotyping flow cytometry panel at week 0 (before vaccination) and week 1 (after vaccination). Our data demonstrate that both DS-Cav1 and MEDI7510 vaccination robustly elicit F-specific antibodies and B cells, but DS-Cav1 elicited antibodies that more potently neutralized both RSV A and B. The superior potency was mediated by antibodies that bind antigenic sites on the apex of pre-F that are not present on post-F. In the memory (CD27) B cell compartment, vaccination with DS-Cav1 or MEDI7510 elicited B cells with different epitope specificities. B cells preferentially binding the pre-F probe were activated in DS-Cav1-vaccinated participants but not in MEDI7510-vaccinated participants. Our findings emphasize the importance of using pre-F as an immunogen in humans because of its deterministic role in eliciting highly potent neutralizing antibodies and memory B cells.
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Examination of pubertal timing and tempo in females and males with autism spectrum disorder compared to typically developing youth.
Autism research : official journal of the International Society for Autism Research (2022)
Corbett BA, Muscatello RA, Kim A, Vandekar S, Duffus S, Sparks S, Tanguturi Y.
Examination of pubertal timing and tempo in females and males with autism spectrum disorder compared to typically developing youth.
Autism Res.
2022 Aug 1;
:.
Abstract: Autism spectrum disorder (ASD) is characterized by impaired social communication and poor adaptation to change; thus, pubertal development may be precarious. Pubertal timing and tempo were measured in 244 youth (7.9% Black, 83.3% White, and 8.7% multiracial) with ASD (N = 140) and typical development (N = 104). Pubertal development was measured using Tanner staging of Genital (G, males), Breast (B, females), and pubic hair (PH) in both sexes at Year 1 (10-13 years), Year 2 (11-14 years), and Year 3 (12-15 years). Nonlinear mixed effects models analyzed interindividual differences in timing and tempo. For both sexes, ASD and higher body mass index were associated with earlier pubertal timing. Males generally exhibited faster tempo than females. Linear regression models did not show associations between pubertal timing and internalizing symptoms at time three. Findings showing advanced pubertal maturation in ASD youth suggest greater risk of psychological, social, and physiological challenges. LAY SUMMARY: Youth with ASD have difficulty in social communication and adaption to change, thus puberty may be a challenging transition. The study examined onset (timing) and progression (tempo) of puberty over three years, using physical exam, in 244 adolescents with and without ASD, enrolled at ages 10-13. ASD youth started puberty earlier, while males generally progressed at a faster pace. Further examination of puberty in ASD should identify impact on social, behavioral, and mental health outcomes.
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Altered Interoceptive Sensibility in Adults With Chronic Tic Disorder.
Frontiers in psychiatry (2022)
Narapareddy A, Eckland MR, Riordan HR, Cascio CJ, Isaacs DA.
Altered Interoceptive Sensibility in Adults With Chronic Tic Disorder.
Front Psychiatry.
2022;
13:914897.
Abstract: Interoception refers to the sensing, interpretation, integration, and regulation of signals about the body's internal physiological state. Interoceptive sensibility is the subjective evaluation of interoceptive experience, as assessed by self-report measures, and is abnormal in numerous neuropsychiatric disorders. Research examining interoceptive sensibility in individuals with chronic tic disorders (CTDs), however, has yielded conflicting results, likely due to methodologic differences between studies and small sample sizes.
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Cognitive phenotypes in late-life depression.
International psychogeriatrics (2022)
Szymkowicz SM, Ryan C, Elson DM, Kang H, Taylor WD.
Cognitive phenotypes in late-life depression.
Int Psychogeriatr.
2022 Jun 29;
:1-13.
Abstract: To identify cognitive phenotypes in late-life depression (LLD) and describe relationships with sociodemographic and clinical characteristics.
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Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial.
Journal of the American Heart Association (2022)
Alsouqi A, Deger SM, Sahinoz M, Mambungu C, Clagett AR, Bian A, Guide A, Stewart TG, Pike M, Robinson-Cohen C, Crescenzi R, Madhur MS, Harrison DG, Ikizler TA.
Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial.
J Am Heart Assoc.
2022 Apr 19;
11(8):e022723.
Abstract: Background Sodium (Na) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na. In this study, we evaluated tissue Na in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na diet. Methods and Results In a double-blinded, placebo-controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (<2 g of sodium), chlorthalidone, spironolactone, or placebo for 8 weeks. Muscle and skin Na using sodium magnetic resonance imaging and pulse wave velocity were assessed at the beginning and end of the study. Ninety-eight patients were enrolled to undergo baseline measurements and 54 completed randomization. Median baseline muscle and skin Na in 98 patients were 16.4 mmol/L (14.9, 18.9) and 13.1 mmol/L (11.1, 16.1), respectively. After 8 weeks, muscle Na increased in the diet and chlorthalidone arms compared with placebo. Skin sodium was decreased only in the diet arm compared with placebo. These associations remained significant after adjustment for age, sex, body mass index, systolic blood pressure, and urinary sodium. No changes were observed in pulse wave velocity among the different groups when compared with placebo. Conclusions Diuretic therapy for 8 weeks did not decrease muscle or skin sodium or improve pulse wave velocity in patients with elevated blood pressure or stage I hypertension. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02236520.
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Test-Retest Reliability and Responsiveness of PROMIS Sleep Short Forms Within an RCT in Women With Fibromyalgia.
Frontiers in pain research (Lausanne, Switzerland) (2021)
Chimenti RL, Rakel BA, Dailey DL, Vance CGT, Zimmerman MB, Geasland KM, Williams JM, Crofford LJ, Sluka KA.
Test-Retest Reliability and Responsiveness of PROMIS Sleep Short Forms Within an RCT in Women With Fibromyalgia.
Front Pain Res (Lausanne).
2021;
2:682072.
Abstract: Nonrestorative sleep is commonly reported by individuals with fibromyalgia, but there is limited information on the reliability and responsiveness of self-reported sleep measures in this population. (1) Examine the reliability and validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in women with fibromyalgia, and (2) Determine the responsiveness of the PROMIS sleep measures to a daily transcutaneous electrical nerve stimulation (TENS) intervention in women with fibromyalgia over 4 weeks compared with other measures of restorative sleep. In a double-blinded, dual-site clinical trial, 301 women with fibromyalgia were randomly assigned to utilize either Active-TENS, Placebo-TENS, or No-TENS at home. Measures were collected at baseline and after 4 weeks of treatment. To assess self-reported sleep, the participants completed three PROMIS short forms: Sleep Disturbance, Sleep-Related Impairment, Fatigue, and the Pittsburgh Sleep Quality Index (PSQI). To assess device-measured sleep, actigraphy was used to quantify total sleep time, wake after sleep onset, and sleep efficiency. Linear mixed models were used to examine the effects of treatment, time, and treatment*time interactions. The PROMIS short forms had moderate test-retest reliability (ICC 0.62 to 0.71) and high internal consistency (Cronbach's alpha 0.89 to 0.92). The PROMIS sleep measures [mean change over 4 weeks, 95% confidence interval (CI)], Sleep Disturbance: -1.9 (-3.6 to -0.3), Sleep-Related Impairment: -3 (-4.6 to -1.4), and Fatigue: -2.4 (-3.9 to -0.9) were responsive to improvement in restorative sleep and specific to the Active-TENS group but not in the Placebo-TENS [Sleep Disturbance: -1.3 (-3 to 0.3), Sleep-Related Impairment: -1.2 (-2.8 to 0.4), Fatigue: -1.1 (-2.7 to 0.9)] or No-TENS [Sleep Disturbance: -0.1 (-1.6 to 1.5), Sleep-Related Impairment: -0.2 (-1.7 to 1.4), Fatigue: -.3 (-1.8 to 1.2)] groups. The PSQI was responsive but not specific with improvement detected in both the Active-TENS: -0.9 (-1.7 to -0.1) and Placebo-TENS: -0.9 (-1.7 to 0) groups but not in the No-TENS group: -0.3 (-1.1 to 0.5). Actigraphy was not sensitive to any changes in restorative sleep with Active-TENS [Sleep Efficiency: -1 (-2.8 to 0.9), Total Sleep Time: 3.3 (-19.8 to 26.4)]. The PROMIS sleep measures are reliable, valid, and responsive to improvement in restorative sleep in women with fibromyalgia. www.ClinicalTrials.gov, identifier: NCT01888640.
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Increased amplitude of hippocampal low frequency fluctuations in early psychosis: A two-year follow-up study.
Schizophrenia research (2022)
McHugo M, Rogers BP, Avery SN, Armstrong K, Blackford JU, Vandekar SN, Roeske MJ, Woodward ND, Heckers S.
Increased amplitude of hippocampal low frequency fluctuations in early psychosis: A two-year follow-up study.
Schizophr Res.
2022 Mar;
241:260-266.
Abstract: Neuroimaging studies have revealed hippocampal hyperactivity in schizophrenia. In the early stage of the illness, hyperactivity is present in the anterior hippocampus and is thought to spread to other regions as the illness progresses. However, there is limited evidence for changes in basal hippocampal function following the onset of psychosis. Resting state functional MRI signal amplitude may be a proxy measure for increased metabolism and disrupted oscillatory activity, both consequences of an excitation/inhibition imbalance underlying hippocampal hyperactivity. Here, we used fractional amplitude of low frequency fluctuations (fALFF) to test the hypothesis of progressive hippocampal hyperactivity in a two-year longitudinal case-control study. We found higher fALFF in the anterior and posterior hippocampus of individuals in the early stage of non-affective psychosis at study entry. Contrary to our hypothesis of progressive hippocampal dysfunction, we found evidence for normalization of fALFF over time in psychosis. Our findings support a model in which hippocampal fALFF is a marker of psychosis vulnerability or acute illness state rather than an enduring feature of the illness.
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Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV.
Frontiers in immunology (2021)
Fuseini H, Smith R, Nochowicz CH, Simmons JD, Hannah L, Wanjalla CN, Gabriel CL, Mashayekhi M, Bailin SS, Castilho JL, Hasty AH, Koethe JR, Kalams SA.
Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV.
Front Immunol.
2021;
12:796898.
Abstract: While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4 T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m, is positively correlated with greater CD4 T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH. We hypothesized that CD4 T cells from obese PLWH have increased cell proliferation and cytokine production compared to cells from lean PLWH, potentially modulated by differential effects of leptin signaling. To test this hypothesis, peripheral blood mononuclear cells from obese and lean PLWH with long-term virologic suppression on the same ART regimen were pretreated with recombinant leptin and then stimulated with anti-CD3/CD28 or PMA/ionomycin to measure Ki67 expression, leptin receptor (LepR) surface expression and cytokine production. In the absence of leptin, Ki67 expression and IL-17A production were significantly higher in CD4 T cells from obese compared to lean PLWH. However, LepR expression was significantly lower on CD4 T cells from obese compared to lean PLWH. After leptin treatment, Ki67 expression was significantly increased in CD4 T cells from obese PLWH compared to the lean participants. Leptin also increased IL-17A production in CD4 T cells from obese healthy controls. In contrast, leptin decreased IL-17A production in CD4 T cells from both obese and lean PLWH. Combined, these results demonstrate that obesity is associated with greater CD4 T cell proliferation among PLWH, and that higher circulating leptin levels in obesity may contribute to improved CD4 T reconstitution in PLWH initiating ART.
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Altered Mitochondrial Homeostasis during Systemic Lupus Erythematosus Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus.
Journal of immunology (Baltimore, Md. : 1950) (2022)
Monteith AJ, Miller JM, Williams JM, Voss K, Rathmell JC, Crofford LJ, Skaar EP.
Altered Mitochondrial Homeostasis during Systemic Lupus Erythematosus Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus.
J Immunol.
2022 Jan 15;
208(2):454-463.
Abstract: Inflammation involves a delicate balance between pathogen clearance and limiting host tissue damage, and perturbations in this equilibrium promote disease. Patients suffering from autoimmune diseases, such as systemic lupus erythematosus (SLE), have higher levels of serum S100A9 protein and increased risk for infection. S100A9 is highly abundant within neutrophils and modulates antimicrobial activity in response to bacterial pathogens. We reasoned that increased serum S100A9 in SLE patients reflects accumulation of S100A9 protein in neutrophils and may indicate altered neutrophil function. In this study, we demonstrate elevated S100A9 protein within neutrophils from SLE patients, and MRL/ mice associates with lower mitochondrial superoxide, decreased suicidal neutrophil extracellular trap formation, and increased susceptibility to infection. Furthermore, increasing mitochondrial superoxide production restored the antibacterial activity of MRL/ neutrophils in response to These results demonstrate that accumulation of intracellular S100A9 associates with impaired mitochondrial homeostasis, thereby rendering SLE neutrophils inherently less bactericidal.
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Standardized two-step testing of antibody activity in COVID-19 convalescent plasma.
iScience (2022)
Gilchuk P, Thomsen I, Yoder S, Brady E, Chappell JD, Stevens LJ, Denison MR, Sutton RE, Chen RE, VanBlargan LA, Suryadevara N, Zost SJ, Schmitz J, Pulley JM, Diamond MS, Rhoads JP, Bernard GR, Self WH, Rice TW, Wheeler AP, Crowe JE Jr, Carnahan RH.
Standardized two-step testing of antibody activity in COVID-19 convalescent plasma.
iScience.
2022 Jan 21;
25(1):103602.
Abstract: The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19.
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Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.
PLoS pathogens (2021)
Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G.
Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.
PLoS Pathog.
2021 Nov;
17(11):e1010016.
Abstract: Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies. Trial registration: ClinicalTrials.gov NCT00801697, NCT00961883, NCT02207920, NCT00125970, NCT02852005).
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Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions.
Lymphatic research and biology (2021)
Donahue PMC, Crescenzi R, Petersen KJ, Garza M, Patel N, Lee C, Chen SC, Donahue MJ.
Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions.
Lymphat Res Biol.
2021 Nov 8;
:.
Abstract: Lipedema is a distinct adipose disorder from obesity necessitating awareness as well as different management approaches to address pain and optimize quality of life (QoL). The purpose of this proof-of-principle study is to evaluate the therapeutic potential of physical therapy interventions in women with lipedema. Participants with Stage 1-2 lipedema and early Stage 0-1 lymphedema ( = 5, age = 38.4 ± 13.4 years, body mass index = 27.2 ± 4.3 kg/m) underwent nine visits of physical therapy in 6 weeks for management of symptoms impacting functional mobility and QoL. Pre- and post-therapy, participants were scanned with 3 Tesla sodium and water magnetic resonance imaging (MRI), underwent biophysical measurements, and completed questionnaires measuring function and QoL (patient-specific functional scale, PSFS, and RAND-36). Pain was measured at each visit using the 0-10 visual analog scale (VAS). Treatment effect was calculated for all study variables. The primary symptomatology measures of pain and function revealed clinically significant post-treatment improvements and large treatment effects (Cohen's for pain VAS = -2.5 and PSFS = 4.4). The primary sodium MRI measures, leg skin sodium, and subcutaneous adipose tissue (SAT) sodium, reduced following treatment and revealed large treatment effects (Cohen's for skin sodium = -1.2 and SAT sodium = -0.9). This proof-of-principle study provides support that persons with lipedema can benefit from physical therapy to manage characteristic symptoms of leg pain and improve QoL. Objective MRI measurement of reduced tissue sodium in the skin and SAT regions indicates reduced inflammation in the treated limbs. Further research is warranted to optimize the conservative therapy approach in lipedema, a condition for which curative and disease-modifying treatments are unavailable.
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A Preliminary Investigation of ERP Components of Attentional Bias in Anxious Adults using Temporospatial Principal Component Analysis.
Journal of psychophysiology (2021)
Gupta RS, Kujawa A, Vago DR.
A Preliminary Investigation of ERP Components of Attentional Bias in Anxious Adults using Temporospatial Principal Component Analysis.
J Psychophysiol.
2021 Oct;
35(4):223-236.
Abstract: Threat-related attention bias is thought to contribute to the development and maintenance of anxiety disorders. Dot-probe studies using event-related potentials (ERPs) have indicated that several early ERP components are modulated by threatening and emotional stimuli in anxious populations, suggesting enhanced allocation of attention to threat and emotion at earlier stages of processing. However, ERP components selected for examination and analysis in these studies vary widely and remain inconsistent. The present study used temporospatial principal component analysis (PCA) to systematically identify ERP components elicited to face pair cues and probes in a dot-probe task in anxious adults. Cue-locked components sensitive to emotion included an early occipital C1 component enhanced for happy versus angry face pair cues and an early parieto-occipital P1 component enhanced for happy versus angry face pair cues. Probe-locked components sensitive to congruency included a parieto-occipital P2 component enhanced for incongruent probes (probes replacing neutral faces) versus congruent probes (probes replacing emotional faces). Split-half correlations indicated that the mean value around the PCA-derived peaks were reliably measured in the ERP waveforms. These results highlight promising neurophysiological markers for attentional bias research that can be extended to designs comparing anxious and healthy comparison groups. Results from a secondary exploratory PCA analysis investigating the effects of emotional face position and analyses on behavioral reaction time data are also presented.
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Effect of nitroglycerin on splanchnic and pulmonary blood volume.
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology (2021)
Okamoto LE, Dupont WD, Biaggioni I, Kronenberg MW.
Effect of nitroglycerin on splanchnic and pulmonary blood volume.
J Nucl Cardiol.
2021 Nov 2;
:.
Abstract: Sublingual nitroglycerin (SL NTG) is useful for treating acute decompensated heart failure, possibly by increasing splanchnic capacitance and reducing left ventricular (LV) preload. We evaluated a radionuclide method to study these effects, initially in subjects without heart failure.
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Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.
Breast cancer research and treatment (2022)
Crescenzi R, Donahue PMC, Garza M, Lee CA, Patel NJ, Gonzalez V, Jones RS, Donahue MJ.
Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.
Breast Cancer Res Treat.
2022 Jan;
191(1):115-124.
Abstract: Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL.
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Effects of financial incentives on volunteering for clinical trials: A randomized vignette experiment.
Contemporary clinical trials (2021)
Bickman L, Domenico HJ, Byrne DW, Jerome RN, Edwards TL, Stroud M, Lebo L, Mcguffin K, Wilkins CH, Harris PA.
Effects of financial incentives on volunteering for clinical trials: A randomized vignette experiment.
Contemp Clin Trials.
2021 Nov;
110:106584.
Abstract: Financial incentives may aid recruitment to clinical trials, but evidence regarding risk/burden-driven variability in participant preferences for incentives is limited. We developed and tested a framework to support real-world decisions on recruitment budget.
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Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery.
International journal of radiation oncology, biology, physics (2022)
Khattab MH, Cmelak AJ, Sherry AD, Luo G, Wang L, Yu H, Hedera P, Phibbs FT, Lindsell CJ, Neimat J, Kirschner AN.
Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery.
Int J Radiat Oncol Biol Phys.
2022 Jan 1;
112(1):121-130.
Abstract: We sought to determine whether a more widely accessible, noninvasive, frameless approach to radiosurgical thalamotomy would improve objective measures of refractory essential or parkinsonian tremor without added toxicity compared with reports of frame-based radiosurgery.
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A REDCap-based model for online interventional research: Parent sleep education in autism.
Journal of clinical and translational science (2021)
Malow BA, Galion A, Lu F, Kennedy N, Lawrence CE, Tassone A, O'Neal L, Wilson TM, Parker RA, Harris PA, Neumeyer AM.
A REDCap-based model for online interventional research: Parent sleep education in autism.
J Clin Transl Sci.
2021;
5(1):e138.
Abstract: The use of online platforms for pediatric healthcare research is timely, given the current pandemic. These platforms facilitate trial efficiency integration including electronic consent, randomization, collection of patient/family survey data, delivery of an intervention, and basic data analysis.
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Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV.
Hepatology communications (2021)
Gabriel CL, Ye F, Fan R, Nair S, Terry JG, Carr JJ, Silver H, Baker P, Hannah L, Wanjalla C, Mashayekhi M, Bailin S, Lima M, Woodward B, Izzy M, Ferguson JF, Koethe JR.
Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV.
Hepatol Commun.
2021 Jul;
5(7):1224-1237.
Abstract: Persons with human immunodeficiency virus (PWH) have subcutaneous adipose tissue (SAT) dysfunction related to antiretroviral therapy and direct viral effects, which may contribute to a higher risk of nonalcoholic fatty liver disease compared with human immunodeficiency virus-negative individuals. We assessed relationships between SAT expression of major adipocyte regulatory and lipid storage genes with hepatic and other ectopic lipid deposits in PWH. We enrolled 97 PWH on long-term antiretroviral therapy with suppressed plasma viremia and performed computed tomography measurements of liver attenuation, a measure of hepatic steatosis, skeletal muscle (SM) attenuation, and the volume of abdominal subcutaneous, visceral, and pericardial adipose tissue. Whole SAT gene expression was measured using the Nanostring platform, and relationships with computed tomography imaging and fasting lipids were assessed using multivariable linear regression and network mapping. The cohort had a mean age of 47 years, body mass index of 33.4 kg/m, and CD4 count of 492 cells/mm. Lower liver attenuation, a marker of greater steatosis, was associated with differences in SAT gene expression, including lower lipoprotein lipase and acyl-CoA dehydrogenase, and higher phospholipid transfer protein. Lower liver attenuation clustered with lower visceral adipose tissue (VAT) attenuation and greater VAT volume, pericardial fat volume and triglycerides, but no relationship was observed between liver attenuation and SAT volume, SM attenuation, or low-density lipoprotein. Liver attenuation was associated with altered SAT expression of genes regulating lipid metabolism and storage, suggesting that SAT dysfunction may contribute to nonalcoholic fatty liver disease in PWH. SAT gene-expression relationships were similar for VAT volume and attenuation, but not SM, indicating that ectopic lipid deposition may involve multiple pathways.
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Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Aβ-PET and cognition.
Journal of neurology, neurosurgery, and psychiatry (2021)
Rauchmann BS, Schneider-Axmann T, Perneczky R, Alzheimer's Disease Neuroimaging Initiative (ADNI)..
Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Aβ-PET and cognition.
J Neurol Neurosurg Psychiatry.
2021 Dec;
92(12):1289-1295.
Abstract: To explore if changes over time of plasma phosphorylated tau (p-tau)181 and neurofilament light chain (NfL) predict future tau and amyloid β (Aβ) PET load and cognitive performance, we studied a subsample of the Alzheimer's disease (AD) neuroimaging cohort with longitudinal blood peptide assessments.
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Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates.
Vaccine (2021)
Wolfe LS, Smedley JG 3rd, Bubna N, Hussain A, Harper R, Mostafa S.
Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates.
Vaccine.
2021 Jun 29;
39(29):3852-3861.
Abstract: Preclinical development of vaccine candidates is an important link between the discovery and manufacture of vaccines for use in human clinical trials. Here, an exploratory clinical study utilizing multiple gp120 envelope proteins as vaccine antigens was pursued, which required a harmonized platform development approach for timely and efficient manufacture of the combined HIV vaccine product. Development of cell lines, processes, and analytical methods was initiated with a transmitted founder envelope protein (CH505TF), then applied to produce three subsequent gp120 Env (envelope) variants. Cell lines were developed using the commercially available Freedom CHO DG44 kit (Life Technologies). The fed-batch cell culture production process was based on a commercially-available medium with harmonized process parameters across the variants. A platform purification process was developed utilizing a mixed mode chromatography capture step, with ceramic hydroxyapatite and ion exchange polishing steps. A suite of analytical methods was developed to establish and monitor the Quality Target Profile (QTP), release and long-term stability testing of the vaccine products. The platform development strategy was successfully implemented to produce four gp120 envelope protein variants. In some cases, minor changes to the platform were required to optimize for a particular variant; however, baseline conditions for the processes (cell line type, media & feed system, chromatography resins, and analytical approaches) remained constant, leading to successful transfer and manufacture of all four proteins in a cGMP facility. This body of work demonstrates successful pursuit of a platform development approach to manufacture important vaccine candidates and can be used as a model for other vaccine glycoproteins, such as HIV gp140 trimers or other viral glycoproteins with global health implications. Clinical trial identifier. NCT03220724, NCT03856996.
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Articulatory Correlates of Stress Pattern Disturbances in Talkers With Dysarthria.
Journal of speech, language, and hearing research : JSLHR (2021)
Kim D, Kuruvilla-Dugdale M, de Riesthal M, Jones R, Bagnato F, Mefferd A.
Articulatory Correlates of Stress Pattern Disturbances in Talkers With Dysarthria.
J Speech Lang Hear Res.
2021 Jun 18;
64(6S):2287-2300.
Abstract: Purpose Reduced stress commonly occurs in talkers with Parkinson's disease (PD), whereas excessive and equal stress is frequently associated with dysarthria of talkers with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). This study sought to identify articulatory impairment patterns that underlie these two impaired stress patterns. We further aimed to determine if talkers with the same stress pattern disturbance but different diseases (ALS and MS) exhibit disease-specific articulatory deficits. Method Fifty-seven talkers participated in the study-33 talkers with dysarthria and 24 controls. Talkers with dysarthria were grouped based on their medical diagnosis: PD ( = 15), ALS ( = 10), MS ( = 8). Participants repeated target words embedded in a carrier phrase. Kinematic data were recorded using electromagnetic articulography. Duration, displacement, peak speed, stiffness, time-to-peak speed, and parameter c were extracted for the initial lower lip opening stroke of each target word, which was either stressed or unstressed. Results Stress effects were significant for all kinematic measures across groups except for stiffness and time-to-peak speed, which were nonsignificant in ALS. For comparisons with controls, more kinematic measures significantly differed in the ALS group than in the PD and MS groups. Additionally, ALS and MS showed mostly similar articulatory impairment patterns. Conclusions In general, significant stress effects were observed in talkers with dysarthria. However, stress-specific between-group differences in articulatory performance, particularly displacement, may explain the perceptual impression of disturbed stress patterns. Furthermore, similar findings for ALS and MS suggest that articulatory deficits underlying similar stress pattern disturbances are not disease-specific.
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Anterior hippocampal dysfunction in early psychosis: a 2-year follow-up study.
Psychological medicine (2021)
McHugo M, Avery S, Armstrong K, Rogers BP, Vandekar SN, Woodward ND, Blackford JU, Heckers S.
Anterior hippocampal dysfunction in early psychosis: a 2-year follow-up study.
Psychol Med.
2021 Apr 20;
:1-10.
Abstract: Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years.
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Early detection of amyloid load using 18F-florbetaben PET.
Alzheimer's research & therapy (2021)
Bullich S, Roé-Vellvé N, Marquié M, Landau SM, Barthel H, Villemagne VL, Sanabria Á, Tartari JP, Sotolongo-Grau O, Doré V, Koglin N, Müller A, Perrotin A, Jovalekic A, De Santi S, Tárraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M.
Early detection of amyloid load using 18F-florbetaben PET.
Alzheimers Res Ther.
2021 Mar 27;
13(1):67.
Abstract: A low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using F-florbetaben PET. Quantitative thresholds for the early (SUVR) and established (SUVR) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition.
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A high-throughput liquid bead array assay confirms strong correlation between SARS-CoV-2 antibody level and COVID-19 severity.
iScience (2021)
Bennett M, Yoder S, Brady E, Pulley JM, Rhoads JP, Stewart TG, Bernard GR, Creech CB, Wheeler AP, Thomsen I.
A high-throughput liquid bead array assay confirms strong correlation between SARS-CoV-2 antibody level and COVID-19 severity.
iScience.
2021 Feb 19;
24(2):102052.
Abstract: A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed. We developed a sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. To determine whether COVID-19 symptom severity correlates with SARS-CoV-2 IgG, we measured anti-RBD IgG levels from 67 subjects recovered from PCR-confirmed COVID-19. We found that COVID-19 symptom severity strongly correlated with RBD IgG level (p < 0.001). These findings have substantial implications for public policy surrounding assessments of antibody responses and possible immunity, as not all cases of COVID-19 can be assumed to generate a protective antibody response, and mild disease in particular is capable of generating very low-level anti-RBD IgG levels. These findings also have important implications for the selection of donors for convalescent plasma to be used therapeutically.
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Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure.
Molecular psychiatry (2021)
Roeske MJ, McHugo M, Vandekar S, Blackford JU, Woodward ND, Heckers S.
Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure.
Mol Psychiatry.
2021 Sep;
26(9):5407-5416.
Abstract: Incomplete hippocampal inversion (IHI) is an anatomical variant of the human brain resulting from an arrest in brain development, especially prevalent in the left hemisphere. We hypothesized that IHI is more common in schizophrenia and contributes to the well-known hippocampal structural differences. We studied 199 schizophrenia patients and 161 healthy control participants with 3 T MRI to establish IHI prevalence and the relationship of IHI with hippocampal volume and asymmetry. IHI was more prevalent (left hemisphere: 15% of healthy control participants, 27% of schizophrenia patients; right hemisphere: 4% of healthy control participants, 10% of schizophrenia patients) and more severe in schizophrenia patients compared to healthy control participants. Severe IHI cases were associated with a higher rate of automated segmentation failure. IHI contributed to smaller hippocampal volume and increased R > L volume asymmetry in schizophrenia. The increased prevalence and severity of IHI supports the neurodevelopmental model of schizophrenia. The impact of this developmental variant deserves further exploration in studies of the hippocampus in schizophrenia.
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Stable habituation deficits in the early stage of psychosis: a 2-year follow-up study.
Translational psychiatry (2021)
Avery SN, McHugo M, Armstrong K, Blackford JU, Woodward ND, Heckers S.
Stable habituation deficits in the early stage of psychosis: a 2-year follow-up study.
Transl Psychiatry.
2021 Jan 5;
11(1):20.
Abstract: Neural habituation, the decrease in brain response to repeated stimuli, is a fundamental, highly conserved mechanism that acts as an essential filter for our complex sensory environment. Convergent evidence indicates neural habituation is disrupted in both early and chronic stages of schizophrenia, with deficits co-occurring in brain regions that show inhibitory dysfunction. As inhibitory deficits have been proposed to contribute to the onset and progression of illness, habituation may be an important treatment target. However, a crucial first step is clarifying whether habituation deficits progress with illness. In the present study, we measured neural habituation in 138 participants (70 early psychosis patients (<2 years of illness), 68 healthy controls), with 108 participants assessed longitudinally at both baseline and 2-year follow-up. At follow-up, all early psychosis patients met criteria for a schizophrenia spectrum disorder (i.e., schizophreniform disorder, schizophrenia, schizoaffective disorder). Habituation slopes (i.e., rate of fMRI signal change) to repeated images were computed for the anterior hippocampus, occipital cortex, and the fusiform face area. Habituation slopes were entered into a linear mixed model to test for effects of group and time by region. We found that early psychosis patients showed habituation deficits relative to healthy control participants across brain regions, and that these deficits were maintained, but did not worsen, over two years. These results suggest a stable period of habituation deficits in the early stage of schizophrenia.
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Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort.
Annals of the American Thoracic Society (2021)
Lakhani DA, Chen SC, Antic S, Muterspaugh A, Cook C, Liu N, Shujat H, Jouan S, Winston B, Fields K, Wenstrup J, Block SL, Hinton A, Miller A, Atmajoana S, Helton JT, Patel K, Balar AB, Brewer K, Nag S, Singh R, Disher A, Huerta L, Fremont R, Rickman O, Ch.
Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort.
Ann Am Thorac Soc.
2021 Jul;
18(7):1227-1234.
Abstract: A prospective longitudinal cohort of individuals at high risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer. The goal of this study is to characterize individuals with high risk for lung cancer, accumulating valuable biospecimens and LDCT chest scans longitudinally over 5 years. Participants 55-80 years of age with a 5-year estimated risk of developing lung cancer >1.5% were recruited and enrolled from clinics at the Vanderbilt University Medical Center, Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent an LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for 5 years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging, and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit. A total of 480 participants were enrolled at study baseline and consented to sharing their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, four squamous cell carcinomas, one large cell neuroendocrine, and one small-cell lung cancer) have been identified. We established a unique prospective cohort of individuals at high risk for lung cancer, enrolled at three institutions, for whom full clinical data, well-annotated LDCT scans, and biospecimens are being collected longitudinally. This repository will allow for the derivation and independent validation of clinical, imaging, and molecular biomarkers of risk for diagnosis of lung cancer.Clinical trial registered with ClinicalTrials.gov (NCT01475500).
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Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial.
Pain (2021)
Bruehl S, Burns JW, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Wu YH, Stone A.
Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial.
Pain.
2021 Aug 1;
162(8):2204-2213.
Abstract: We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Patients with chronic back pain were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent 3 laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on visual analogue scale back pain intensity was observed (P = 0.046), with a similar trend for evoked pain threshold (P = 0.093). Male exercisers showed reduced morphine analgesia pre-post intervention, whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine preintervention (P < 0.045). Greater pre-post intervention increases in endogenous opioid function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (P < 0.046). The overall pattern of findings suggests that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.
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Qualitative Analysis of Treatment Needs in Interstitial Cystitis/Bladder Pain Syndrome: Implications for Intervention.
Canadian journal of pain = Revue canadienne de la douleur (2020)
McKernan LC, Bonnet KR, Finn MTM, Williams DA, Bruehl S, Reynolds WS, Clauw D, Dmochowski RR, Schlundt DG, Crofford LJ.
Qualitative Analysis of Treatment Needs in Interstitial Cystitis/Bladder Pain Syndrome: Implications for Intervention.
Can J Pain.
2020;
4(1):181-198.
Abstract: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know if such treatments would meet patient needs.
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Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia.
Pain (2021)
Vance CGT, Zimmerman MB, Dailey DL, Rakel BA, Geasland KM, Chimenti RL, Williams JM, Golchha M, Crofford LJ, Sluka KA.
Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia.
Pain.
2021 May 1;
162(5):1545-1555.
Abstract: We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM.
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Camouflaging in Autism: Examining Sex-Based and Compensatory Models in Social Cognition and Communication.
Autism research : official journal of the International Society for Autism Research (2021)
Corbett BA, Schwartzman JM, Libsack EJ, Muscatello RA, Lerner MD, Simmons GL, White SW.
Camouflaging in Autism: Examining Sex-Based and Compensatory Models in Social Cognition and Communication.
Autism Res.
2021 Jan;
14(1):127-142.
Abstract: Camouflaging refers to behavioral adaptations that individuals with autism spectrum disorder (ASD), especially females, use to mask symptoms during social situations. Compensation is a component of camouflaging in which an individual's observed behavior is considerably better than actual ability. The study explored diagnostic, sex-based, and compensatory differences using the Contextual Assessment of Social Skills (CASS). The sample included 161 youth 10:0-to-16:11 years (115 males, 46 females). T-tests were performed based on sex (female, male) or High (good ADOS + poor Theory of Mind (TOM)) compared to Low (poor ADOS + poor TOM) Compensation groups. Comparisons were examined for Social Affect (SA), Restricted Repetitive Behavior, (RRB), IQ, social behavior (Positive Affect, Overall Involvement) and communication (Vocal Expression, Gestures). Females exhibited fewer RRB t(158) = 3.05, P = 0.003, d = 0.54. For the CASS, females evidenced more Vocal Expressiveness t(157) = -2.03, P = 0.05, d = 0.35, which corroborates sex-based differences in the literature. Compensation group differences indicated the High compared to Low group showed stronger Social and Communication behaviors on the CASS for Vocal Expression t(72) = 2.56, P = 0.01, d = 0.62, and overall rapport t(72) = 2.36, P = 0.02, d = 0.56. Several differences were observed when the groups were stratified based on level of compensation, with the High compensation participants showing stronger social engagement and communication behaviors. Findings may inform efforts to understand camouflaging, compensation, and clinical practices for male and female adolescents with ASD. A more nuanced consideration of camouflaging alongside compensation models reveals subtle differences in cognition, behavior, and affect that may reflect underlying profiles of challenge and strength in youth with ASD. LAY SUMMARY: Camouflaging refers to ways individuals with autism spectrum disorder (ASD), especially females, mask symptoms. Compensation occurs when a person's observed behavior appears more typical than what would be expected based on underlying ability and symptoms. The study explored camouflaging and compensation differences in 161 youth with ASD. Findings suggest sex-based differences with females showing better vocal expression. However, several compensation differences were observed with the High compensators showing stronger social communication and rapport. A more nuanced consideration of camouflaging using compensation models reveal subtle differences in underlying challenge and strength.
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A potential role for zinc in restless legs syndrome.
Sleep (2021)
Chen P, Bornhorst J, Patton S, Bagai K, Nitin R, Miah M, Hare DJ, Kysenius K, Crouch PJ, Xiong L, Rouleau GA, Schwerdtle T, Connor J, Aschner M, Bowman AB, Walters AS.
A potential role for zinc in restless legs syndrome.
Sleep.
2021 Apr 9;
44(4):.
Abstract: Evaluate serum and brain noniron metals in the pathology and genetics of restless legs syndrome (RLS).
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Sensory Hypersensitivity Severity and Association with Obsessive-Compulsive Symptoms in Adults with Tic Disorder.
Neuropsychiatric disease and treatment (2020)
Isaacs D, Key AP, Cascio CJ, Conley AC, Walker HC, Wallace MT, Claassen DO.
Sensory Hypersensitivity Severity and Association with Obsessive-Compulsive Symptoms in Adults with Tic Disorder.
Neuropsychiatr Dis Treat.
2020;
16:2591-2601.
Abstract: Sensory hypersensitivity, defined as heightened awareness of and reactivity to external stimuli, is a bothersome symptom that affects up to 80% of adults with Tourette syndrome (TS). Such widespread prevalence suggests sensory hypersensitivity is a core feature of the disorder, but its severity and association with other clinical features of TS remain largely unexplored. Complicating matters, sensory hypersensitivity has been observed in two neurodevelopmental disorders commonly comorbid with TS: obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD).
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Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data.
Diabetes, obesity & metabolism (2021)
Peters A, Cohen N, Calhoun P, Ruedy KJ, Beck RW, Martens TW, Bao S, Njeru NM, Beck SE, Price DA.
Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data.
Diabetes Obes Metab.
2021 Feb;
23(2):631-636.
Abstract: Basal insulin is often prescribed to patients with suboptimally controlled type 2 diabetes (T2D); however, its therapeutic efficacy is inadequate in many. During the MOBILE study's baseline phase, we evaluated 173 participants' continuous glucose monitoring (CGM) data (mean ± SD age 57 ± 9 years; 50% female; HbA1c 9.1% [range 7.1%-11.6%]; 40% using sulphonylureas; 19% using NPH; reported self-monitored blood glucose [SMBG] frequency median 1.0 checks/day) who were using basal, but not prandial insulin. Blinded CGM data were recorded for 10 days prior to randomization. The mean glucose value was 208 ± 47 mg/dL and it was lowest in the early morning. Mean time in the 70-180 mg/dL range was 9.6 ± 6.1 hours/day (40% ± 25%). Hyperglycaemia was extensive with medians of 14.7 (61%) and 5.0 (20.9%) hours/day with glucose greater than 180 and 250 mg/dL, respectively. Hypoglycaemia was infrequent (median [IQR] 0 [0, 4.3] minutes/day [0.0% {0.0%, 0.3%}] with glucose less than 70 mg/dL). Blinded CGM highlights the limitations of infrequent SMBG in basal insulin users with T2D and allows characterization of hyperglycaemia and hypoglycaemia in basal insulin users with suboptimal control. The MOBILE study randomized phase will define the benefits of using real-time CGM compared with SMBG in this population.
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Relational memory in the early stage of psychotic bipolar disorder.
Psychiatry research (2020)
McKinney RA, Avery SN, Armstrong K, Blackford JU, Woodward ND, Heckers S.
Relational memory in the early stage of psychotic bipolar disorder.
Psychiatry Res.
2020 Dec;
294:113508.
Abstract: Relational memory is impaired in psychotic disorders. In non-affective psychotic disorders, relational memory deficits are present in the early stage of illness and become more pronounced in the chronic stage. Previous studies have demonstrated cognitive deficits in early-stage psychotic bipolar disorder, but it is unclear whether relational memory is impaired. We examined relational memory using a face-scene binding task in early-stage psychotic bipolar disorder patients (n = 33) and compared their performance with healthy control (n = 40) and early-stage non-affective psychosis participants (n = 40). During training, participants learned to associate faces with background scenes. During testing, participants viewed a scene overlaid by three faces and were asked to recall the matching face. Relational memory was assessed indirectly using eye movements and explicitly using forced-choice recognition. Preferential viewing of the matching face, as captured by overall proportion of viewing and viewing across time, was significantly lower in psychotic bipolar disorder than in the healthy control group. However, preferential viewing of the matching face in psychotic bipolar disorder was significantly better than in non-affective psychosis. These findings provide novel evidence that relational memory in patients with early-stage psychotic bipolar disorder is intermediate between healthy control and early-stage non-affective psychosis subjects.
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Pubertal Timing During Early Adolescence: Advanced Pubertal Onset in Females with Autism Spectrum Disorder.
Autism research : official journal of the International Society for Autism Research (2020)
Corbett BA, Vandekar S, Muscatello RA, Tanguturi Y.
Pubertal Timing During Early Adolescence: Advanced Pubertal Onset in Females with Autism Spectrum Disorder.
Autism Res.
2020 Dec;
13(12):2202-2215.
Abstract: Autism spectrum disorder (ASD) is characterized by impaired social communication and poor adaptation to change; thus, the onset of puberty may be a pivotal transition. This cross-sectional study measured pubertal timing to examine hypothesized differences for sex (female vs. male) and group (ASD vs. typical development [TD]). Participants included 239 children (137 ASD, 102 TD) between 10 and 13 years. The ASD group included 35 females and 102 males; the TDs included 44 females and 58 males. Pubertal onset measured by genital or pubic stage was investigated with linear regression using main effects of sex and age-by-sex interactions in TD and ASD groups and main effects of diagnosis and diagnosis-by-age interactions in males and females, controlling for body mass index, socioeconomic status, and race. In TD, examination of main effects for genital (penis/breast) stage showed no difference for male and female children (t = 1.33, P = 0.187, rdf = 92); however, there were significant differences in ASD (t = 2.70, P = 0.008, rdf = 121). For diagnosis modeled separately by sex, there was significantly earlier pubertal development in females with ASD (t = 1.97, P = 0.053, rdf = 70, but not males (t = 1.329, P = 0.186, rdf = 143). In addition, analysis of menses revealed females with ASD had significantly earlier onset than TD (t = -2.56, P = 0.018, rdf = 21). Examination of pubic stage revealed expected sex differences for TD (t = 2,674, P = 0.009, rdf = 91) and ASD (t = 3.482, P = 0.001, rdf = 121). Females with ASD evidence advanced pubertal onset relative to ASD males and TD females. Findings underscore the need for enhanced understanding of pubertal development in ASD, as differences may have significant psychological, social, physiological, and developmental consequences. LAY SUMMARY: Children with autism spectrum disorder (ASD) have difficulty with social communication and respond poorly to change, which may include the onset and course of puberty. The study measured the timing of puberty in 239 children (137 ASD and 102 typical development [TD]) between 10 and 13 years based on pubertal stage of genital (breast/penis) and pubic hair development. Females with ASD evidence advanced pubertal onset relative to ASD males and TD females. Findings underscore the need for an enhanced understanding of pubertal development in ASD.
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Preliminary Evidence That Cortical Amyloid Burden Predicts Poor Response to Antidepressant Medication Treatment in Cognitively Intact Individuals With Late-Life Depression.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry (2021)
Taylor WD, Boyd BD, Elson D, Andrews P, Albert K, Vega J, Newhouse PA, Woodward ND, Kang H, Shokouhi S.
Preliminary Evidence That Cortical Amyloid Burden Predicts Poor Response to Antidepressant Medication Treatment in Cognitively Intact Individuals With Late-Life Depression.
Am J Geriatr Psychiatry.
2021 May;
29(5):448-457.
Abstract: Amyloid accumulation, the pathological hallmark of Alzheimer's disease, may predispose some older adults to depression and cognitive decline. Deposition of amyloid also occurs prior to the development of cognitive decline. It is unclear whether amyloid influences antidepressant outcomes in cognitively intact depressed elders.
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IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia.
Pain (2021)
Merriwether EN, Agalave NM, Dailey DL, Rakel BA, Kolker SJ, Lenert ME, Spagnola WH, Lu Y, Geasland KM, Allen LH, Burton MD, Sluka KA.
IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia.
Pain.
2021 May 1;
162(5):1468-1482.
Abstract: Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. Lipopolysaccharide-evoked and spontaneous secretion of IL-5 and other select cytokines from circulating monocytes was higher in women with FM compared to women without pain. In addition, greater secretion of IL-5 was significantly associated with pain and other clinically relevant psychological and somatic symptoms of FM. Furthermore, higher levels of pain and pain-related symptoms were associated with a lower percentage of intermediate monocytes (CD14++/CD16+) and a greater percentage of nonclassical monocytes (CD14+/CD16++) in women with FM. Based on findings from individuals with FM, we examined the role of IL-5, an atypical cytokine secreted from monocytes, in an animal model of widespread muscle pain. Results from the animal model show that IL-5 produces analgesia and polarizes monocytes toward an anti-inflammatory phenotype (CD206+). Taken together, our data suggest that monocyte phenotype and their cytokine profiles are associated with pain-related symptoms in individuals with FM. Furthermore, our data show that IL-5 has a potential role in analgesia in an animal model of FM. Thus, targeting anti-inflammatory cytokines such as IL-5 secreted by circulating leukocytes could serve as a promising intervention to control pain and other somatic symptoms associated with FM.
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Association of a glucagon-like peptide-1 receptor gene variant with glucose response to a mixed meal.
Diabetes, obesity & metabolism (2021)
Mashayekhi M, Wilson JR, Jafarian-Kerman S, Nian H, Yu C, Shuey MM, Luther JM, Brown NJ.
Association of a glucagon-like peptide-1 receptor gene variant with glucose response to a mixed meal.
Diabetes Obes Metab.
2021 Jan;
23(1):281-286.
Abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.
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Accelerated brain aging predicts impaired cognitive performance and greater disability in geriatric but not midlife adult depression.
Translational psychiatry (2020)
Christman S, Bermudez C, Hao L, Landman BA, Boyd B, Albert K, Woodward N, Shokouhi S, Vega J, Andrews P, Taylor WD.
Accelerated brain aging predicts impaired cognitive performance and greater disability in geriatric but not midlife adult depression.
Transl Psychiatry.
2020 Sep 18;
10(1):317.
Abstract: Depression is associated with markers of accelerated aging, but it is unclear how this relationship changes across the lifespan. We examined whether a brain-based measure of accelerated aging differed between depressed and never-depressed subjects across the adult lifespan and whether it was related to cognitive performance and disability. We applied a machine-learning approach that estimated brain age from structural MRI data in two depressed cohorts, respectively 170 midlife adults and 154 older adults enrolled in studies with common entry criteria. Both cohorts completed broad cognitive batteries and the older subgroup completed a disability assessment. The machine-learning model estimated brain age from MRI data, which was compared to chronological age to determine the brain-age gap (BAG; estimated age-chronological age). BAG did not differ between midlife depressed and nondepressed adults. Older depressed adults exhibited significantly higher BAG than nondepressed elders (Wald χ = 8.84, p = 0.0029), indicating a higher estimated brain age than chronological age. BAG was not associated with midlife cognitive performance. In the older cohort, higher BAG was associated with poorer episodic memory performance (Wald χ = 4.10, p = 0.0430) and, in the older depressed group alone, slower processing speed (Wald χ = 4.43, p = 0.0354). We also observed a statistical interaction where greater depressive symptom severity in context of higher BAG was associated with poorer executive function (Wald χ = 5.89, p = 0.0152) and working memory performance (Wald χ = 4.47, p = 0.0346). Increased BAG was associated with greater disability (Wald χ = 6.00, p = 0.0143). Unlike midlife depression, geriatric depression exhibits accelerated brain aging, which in turn is associated with cognitive and functional deficits.
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Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps.
PloS one (2020)
Schilling KG, Blaber J, Hansen C, Cai L, Rogers B, Anderson AW, Smith S, Kanakaraj P, Rex T, Resnick SM, Shafer AT, Cutting LE, Woodward N, Zald D, Landman BA.
Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps.
PLoS One.
2020;
15(7):e0236418.
Abstract: Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require data acquired with reverse phase encoding directions, resulting in varying magnitudes and orientations of distortion, which allow estimation of an undistorted volume. Alternatively, additional field maps acquisitions can be used along with sequence information to determine warping fields. However, not all imaging protocols include these additional scans and cannot take advantage of state-of-the art distortion correction. To avoid additional acquisitions, structural MRI (undistorted scans) can be used as registration targets for intensity driven correction. In this study, we aim to (1) enable susceptibility distortion correction with historical and/or limited diffusion datasets that do not include specific sequences for distortion correction and (2) avoid the computationally intensive registration procedure typically required for distortion correction using structural scans. To achieve these aims, we use deep learning (3D U-nets) to synthesize an undistorted b0 image that matches geometry of structural T1w images and intensity contrasts from diffusion images. Importantly, the training dataset is heterogenous, consisting of varying acquisitions of both structural and diffusion. We apply our approach to a withheld test set and show that distortions are successfully corrected after processing. We quantitatively evaluate the proposed distortion correction and intensity-based registration against state-of-the-art distortion correction (FSL topup). The results illustrate that the proposed pipeline results in b0 images that are geometrically similar to non-distorted structural images, and more closely match state-of-the-art correction with additional acquisitions. In addition, we show generalizability of the proposed approach to datasets that were not in the original training / validation / testing datasets. These datasets included varying populations, contrasts, resolutions, and magnitudes and orientations of distortion and show efficacious distortion correction. The method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation.
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Splanchnic Venous Compression Enhances the Effects of ß-Blockade in the Treatment of Postural Tachycardia Syndrome.
Journal of the American Heart Association (2020)
Smith EC, Diedrich A, Raj SR, Gamboa A, Shibao CA, Black BK, Peltier A, Paranjape SY, Biaggioni I, Okamoto LE.
Splanchnic Venous Compression Enhances the Effects of ß-Blockade in the Treatment of Postural Tachycardia Syndrome.
J Am Heart Assoc.
2020 Jul 21;
9(14):e016196.
Abstract: Background Splanchnic venous pooling induced by upright posture triggers a compensatory increase in heart rate (HR), a response that is exaggerated in patients with postural tachycardia syndrome. To assess whether abdominal compression attenuates orthostatic tachycardia and improves symptoms, 18 postural tachycardia syndrome patients (32±2 years) were randomized to receive either abdominal compression (40 mm Hg applied with an inflatable binder ≈2 minutes before standing) or propranolol (20 mg) in a placebo-controlled, crossover study. Methods and Results Systolic blood pressure, HR, and symptoms were assessed while seated and standing, before and 2 hours postdrug. As expected, propranolol decreased standing HR compared with placebo (81±2 versus 98±4 beats per minute; <0.001) and was associated with lower standing systolic blood pressure (93±2 versus 100±2 mm Hg for placebo; =0.002). Compression had no effect on standing HR (96±4 beats per minute) but increased standing systolic blood pressure compared with placebo and propranolol (106±2 mm Hg; <0.01). Neither propranolol nor compression improved symptoms compared with placebo. In 16 patients we compared the combination of abdominal compression and propranolol with propranolol alone. The combination had no additional effect on standing HR (81±2 beats per minute for both interventions) but prevented the decrease in standing systolic blood pressure produced by propranolol (98±2 versus 93±2 mm Hg for propranolol; =0.029), and significantly improved total symptom burden (-6±2 versus -1±2 for propranolol; =0.041). Conclusions Splanchnic venous compression alone did not improve HR or symptoms but prevented the blood pressure decrease produced by propranolol. The combination was more effective in improving symptoms than either alone. Splanchnic venous compression can be a useful adjuvant therapy to propranolol in postural tachycardia syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00262470.
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Detection of Articulatory Deficits in Parkinson's Disease: Can Systematic Manipulations of Phonetic Complexity Help?
Journal of speech, language, and hearing research : JSLHR (2020)
Kuruvilla-Dugdale M, Salazar M, Zhang A, Mefferd AS.
Detection of Articulatory Deficits in Parkinson's Disease: Can Systematic Manipulations of Phonetic Complexity Help?
J Speech Lang Hear Res.
2020 Jul 20;
63(7):2084-2098.
Abstract: Purpose This study sought to determine the feasibility of using phonetic complexity manipulations as a way to systematically assess articulatory deficits in talkers with progressive dysarthria due to Parkinson's disease (PD). Method Articulatory kinematics were recorded using three-dimensional electromagnetic articulography from 15 talkers with PD (58-84 years old) and 15 healthy controls (55-80 years old) while they produced target words embedded in a carrier phrase. Majority of the talkers with PD exhibited a relatively mild dysarthria. For stimuli selection, phonetic complexity was calculated for a variety of words using the framework proposed by Kent (1992), and six words representative of low, medium, and high phonetic complexity were selected as targets. Jaw, posterior tongue, and anterior tongue kinematic measures that were used to test for phonetic complexity effects included movement speed, cumulative path distance, movement range, movement duration, and spatiotemporal variability. Results Significantly smaller movements and slower movement speeds were evident in talkers with PD, predominantly for words with high phonetic complexity. The effect sizes of between-groups differences were larger for several jaw kinematic measures than those of the tongue. Discussion and Conclusion Findings suggest that systematic manipulations of phonetic complexity can support the detection of articulatory deficits in talkers with PD. Phonetic complexity should therefore be leveraged for the assessment of articulatory performance in talkers with progressive dysarthria. Future work will be directed toward linking speech kinematic and auditory-perceptual measures to determine the clinical significance of the current findings.
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Persistence of HIV-1 Env-Specific Plasmablast Lineages in Plasma Cells after Vaccination in Humans.
Cell reports. Medicine (2020)
Basu M, Piepenbrink MS, Francois C, Roche F, Zheng B, Spencer DA, Hessell AJ, Fucile CF, Rosenberg AF, Bunce CA, Liesveld J, Keefer MC, Kobie JJ.
Persistence of HIV-1 Env-Specific Plasmablast Lineages in Plasma Cells after Vaccination in Humans.
Cell Rep Med.
2020 May 19;
1(2):.
Abstract: Induction of persistent HIV-1 Envelope (Env) specific antibody (Ab) is a primary goal of HIV vaccine strategies; however, it is unclear whether HIV Env immunization in humans induces bone marrow plasma cells, the presumed source of long-lived systemic Ab. To define the features of Env-specific plasma cells after vaccination, samples were obtained from HVTN 105, a phase I trial testing the same gp120 protein immunogen, AIDSVAX B/E, used in RV144, along with a DNA immunogen in various prime and boost strategies. Boosting regimens that included AIDSVAX B/E induced robust peripheral blood plasmablast responses. The Env-specific immunoglobulin repertoire of the plasmablasts is dominated by VH1 gene usage and targeting of the V3 region. Numerous plasmablast-derived immunoglobulin lineages persisted in the bone marrow >8 months after immunization, including in the CD138 long-lived plasma cell compartment. These findings identify a cellular linkage for the development of sustained Env-specific Abs following vaccination in humans.
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Exploring the links among borderline personality disorder symptoms, trauma, and pain in patients with chronic pain disorders.
Journal of psychosomatic research (2020)
Johnson BN, Lumley MA, Cheavens JS, McKernan LC.
Exploring the links among borderline personality disorder symptoms, trauma, and pain in patients with chronic pain disorders.
J Psychosom Res.
2020 Aug;
135:110164.
Abstract: Chronic pain and borderline personality disorder (BPD) are commonly comorbid and jointly associated with increased symptoms of both disorders and clinical and functional impairment. Little is known, however, about specific links between these disorders. In a cross-sectional study of patients with chronic pain, we compared participants high or low on BPD symptoms on patterns of pain experience and types of child and adult traumas.
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Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial.
Pain (2020)
Bruehl S, Burns JW, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Wu YH, Qu'd D, Stone A.
Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial.
Pain.
2020 Dec;
161(12):2887-2897.
Abstract: Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). Before and after the intervention, participants underwent separate laboratory sessions to assess responses to evoked heat pain after receiving saline placebo or intravenous naloxone (opioid antagonist) in a double-blinded, crossover fashion. Chronic pain intensity and interference were assessed before and after the intervention. Endogenous opioid analgesia was indexed by naloxone-placebo condition differences in evoked pain responses (blockade effects). Relative to controls, exercise participants reported significantly greater pre-post intervention decreases in chronic pain intensity and interference (Ps < 0.04) and larger reductions in placebo condition evoked pain responsiveness (McGill Pain Questionnaire-Short Form [MPQ]-Total). At the group level, EO analgesia (MPQ-Total blockade effects) increased significantly pre-post intervention only among female exercisers (P = 0.03). Dose-response effects were suggested by a significant positive association in the exercise group between exercise intensity (based on meeting heart rate targets) and EO increases (MPQ-Present Pain Intensity; P = 0.04). Enhanced EO analgesia (MPQ-Total) was associated with a significantly greater improvement in average chronic pain intensity (P = 0.009). Aerobic exercise training in the absence of other interventions appears effective for CLBP management. Aerobic exercise-related enhancements in endogenous pain inhibition, in part EO-related, likely contribute to these benefits.
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Receptivity of Hospitalized Older Adults and Family Caregivers to Prognostic Information about Aging, Injury, and Frailty: A Qualitative Study.
International journal of nursing studies (2020)
Maxwell CA, Mixon AS, Conner E, Phillippi JC.
Receptivity of Hospitalized Older Adults and Family Caregivers to Prognostic Information about Aging, Injury, and Frailty: A Qualitative Study.
Int J Nurs Stud.
2020 Sep;
109:103602.
Abstract: Frailty is the leading prognosticator for poor outcomes and palliative care among older adults. Delivery of negative prognostic information entails potentially difficult conversations about decline and death.
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Elevated Eosinophils as a Feature of Inflammation Associated With Hypertension in Virally Suppressed People Living With HIV.
Journal of the American Heart Association (2020)
Masenga SK, Elijovich F, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, Mutale W, Munsaka SM, Zhao S, Koethe JR, Kirabo A.
Elevated Eosinophils as a Feature of Inflammation Associated With Hypertension in Virally Suppressed People Living With HIV.
J Am Heart Assoc.
2020 Feb 18;
9(4):e011450.
Abstract: Background People living with HIV (PLWH) are at increased risk of cardiovascular disease, including hypertension, which persists despite effective plasma viral suppression on antiretroviral therapy. HIV infection is characterized by long-term alterations in immune function, but the contribution of immune factors to hypertension in PLWH is not fully understood. Prior studies have found that both innate and adaptive immune cell activation contributes to hypertension. Methods and Results We hypothesized that chronic inflammation may contribute to hypertension in PLWH. To test this hypothesis, we enrolled a cohort of 70 PLWH (44% hypertensive) on a long-term single antiretroviral therapy regimen for broad phenotyping of inflammation biomarkers. We found that hypertensive PLWH had higher levels of inflammatory cytokines, including tumor necrosis factor-α receptor 1, interleukin-6, interleukin-17, interleukin-5, intercellular adhesion molecule 1 and macrophage inflammatory protein-1α. After adjustment for age, sex, and fat mass index, the circulating eosinophils remained significantly associated with hypertension. On the basis of these results, we assessed the relationship of eosinophils and hypertension in 2 cohorts of 50 and 81 039 similar HIV-negative people; although eosinophil count was associated with prevalent hypertension, this relationship was abrogated by body mass index. Conclusions These findings may represent a unique linkage between immune status and cardiovascular physiological characteristics in HIV infection, which should be evaluated further.
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At the Research-Clinical Interface: Returning Individual Genetic Results to Research Participants.
Clinical journal of the American Society of Nephrology : CJASN (2020)
West KM, Blacksher E, Cavanaugh KL, Fullerton SM, Umeukeje EM, Young BA, Burke W.
At the Research-Clinical Interface: Returning Individual Genetic Results to Research Participants.
Clin J Am Soc Nephrol.
2020 Aug 7;
15(8):1181-1189.
Abstract: Whether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.
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Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.
Journal of the American Academy of Child and Adolescent Psychiatry (2021)
Malow BA, Findling RL, Schroder CM, Maras A, Breddy J, Nir T, Zisapel N, Gringras P.
Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.
J Am Acad Child Adolesc Psychiatry.
2021 Feb;
60(2):252-261.e3.
Abstract: A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder. This study examined the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development.
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BNST-insula structural connectivity in humans.
NeuroImage (2020)
Flook EA, Feola B, Avery SN, Winder DG, Woodward ND, Heckers S, Blackford JU.
BNST-insula structural connectivity in humans.
Neuroimage.
2020 Apr 15;
210:116555.
Abstract: The bed nucleus of the stria terminalis (BNST) is emerging as a critical region in multiple psychiatric disorders including anxiety, PTSD, and alcohol and substance use disorders. In conjunction with growing knowledge of the BNST, an increasing number of studies examine connections of the BNST and how those connections impact BNST function. The importance of this BNST network is highlighted by rodent studies demonstrating that projections from other brain regions regulate BNST activity and influence BNST-related behavior. While many animal and human studies replicate the components of the BNST network, to date, structural connections between the BNST and insula have only been described in rodents and have yet to be shown in humans. In this study, we used probabilistic tractography to examine BNST-insula structural connectivity in humans. We used two methods of dividing the insula: 1) anterior and posterior insula, to be consistent with much of the existing insula literature; and 2) eight subregions that represent informative cytoarchitectural divisions. We found evidence of a BNST-insula structural connection in humans, with the strongest BNST connectivity localized to the anteroventral insula, a region of agranular cortex. BNST-insula connectivity differed by hemisphere and was moderated by sex. These results translate rodent findings to humans and lay an important foundation for future studies examining the role of BNST-insula pathways in psychiatric disorders.
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Transcutaneous Electrical Nerve Stimulation Reduces Movement-Evoked Pain and Fatigue: A Randomized, Controlled Trial.
Arthritis & rheumatology (Hoboken, N.J.) (2020)
Dailey DL, Vance CGT, Rakel BA, Zimmerman MB, Embree J, Merriwether EN, Geasland KM, Chimenti R, Williams JM, Golchha M, Crofford LJ, Sluka KA.
Transcutaneous Electrical Nerve Stimulation Reduces Movement-Evoked Pain and Fatigue: A Randomized, Controlled Trial.
Arthritis Rheumatol.
2020 May;
72(5):824-836.
Abstract: Fibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. This study was undertaken to investigate if using TENS during activity would improve movement-evoked pain and other patient-reported outcomes in women with FM.
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Twelve-Month-Old Infants Respond to Speech About Absent Inaccessible Objects.
Child development (2020)
Osina MA, Needham AW, Saylor MM.
Twelve-Month-Old Infants Respond to Speech About Absent Inaccessible Objects.
Child Dev.
2020 Jul;
91(4):1353-1363.
Abstract: This article investigated the interplay of 12-month-old infants' perception of affordances for locomotion and their ability to respond to the mention of hidden objects. In Experiment I, a toy was hidden in an ottoman that was placed on a cabinet out of infants' reach. Infants were more likely to look at, point to or approach the ottoman when there were stairs leading to it than when there were none. The stairs did not help infants respond by highlighting the target corner of the room (Experiment II) or by boosting their engagement with the study events (Experiment III). This suggests that infants' perception of the accessibility of the hiding location influences their ability to respond to speech about absent things.
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Hyperactivity and Reduced Activation of Anterior Hippocampus in Early Psychosis.
The American journal of psychiatry (2019)
McHugo M, Talati P, Armstrong K, Vandekar SN, Blackford JU, Woodward ND, Heckers S.
Hyperactivity and Reduced Activation of Anterior Hippocampus in Early Psychosis.
Am J Psychiatry.
2019 Dec 1;
176(12):1030-1038.
Abstract: In schizophrenia, the anterior hippocampus is hyperactive and shows reduced task-related recruitment, but the relationship between these two findings is unclear. The authors tested the hypothesis that hyperactivity impairs recruitment of the anterior hippocampus during scene processing.
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The neural chronometry of threat-related attentional bias: Event-related potential (ERP) evidence for early and late stages of selective attentional processing.
International journal of psychophysiology : official journal of the International Organization of Psychophysiology (2019)
Gupta RS, Kujawa A, Vago DR.
The neural chronometry of threat-related attentional bias: Event-related potential (ERP) evidence for early and late stages of selective attentional processing.
Int J Psychophysiol.
2019 Dec;
146:20-42.
Abstract: Rapid and accurate detection of threat is adaptive. Yet, threat-related attentional biases, including hypervigilance, avoidance, and attentional disengagement delays, may contribute to the etiology and maintenance of anxiety disorders. Behavioral measures of attentional bias generally indicate that threat demands more attentional resources; however, indices exploring differential allocation of attention using reaction time fail to clarify the time course by which attention is deployed under threatening circumstances in healthy and anxious populations. In this review, we conduct an interpretive synthesis of 28 attentional bias studies focusing on event-related potentials (ERPs) as a primary outcome to inform an ERP model of the neural chronometry of attentional bias in healthy and anxious populations. The model posits that both healthy and anxious populations display modulations of early ERP components, including the P1, N170, P2, and N2pc, in response to threatening and emotional stimuli, suggesting that both typical and abnormal patterns of attentional bias are characterized by enhanced allocation of attention to threat and emotion at earlier stages of processing. Compared to anxious populations, healthy populations more clearly demonstrate modulations of later components, such as the P3, indexing conscious and evaluative processing of threat and emotion and disengagement difficulties at later stages of processing. Findings from the interpretive synthesis, existing bias models, and extant neural literature on attentional systems are then integrated to inform a conceptual model of the processes and substrates underlying threat appraisal and resource allocation in healthy and anxious populations. To conclude, we discuss therapeutic interventions for attentional bias and future directions.
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DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial.
The Journal of clinical investigation (2019)
Rouphael NG, Morgan C, Li SS, Jensen R, Sanchez B, Karuna S, Swann E, Sobieszczyk ME, Frank I, Wilson GJ, Tieu HV, Maenza J, Norwood A, Kobie J, Sinangil F, Pantaleo G, Ding S, McElrath MJ, De Rosa SC, Montefiori DC, Ferrari G, Tomaras GD, Keefer MC, HVTN.
DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial.
J Clin Invest.
2019 Nov 1;
129(11):4769-4785.
Abstract: BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein).METHODSOne hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit.RESULTSAll regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%-100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%-100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%-64%) without appreciable CD8+ T cell responses.CONCLUSIONThe DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2-binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses.TRIAL REGISTRATIONClinicalTrials.gov NCT02207920.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).
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Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome.
The Journal of clinical endocrinology and metabolism (2020)
Devin JK, Nian H, Celedonio JE, Wright P, Brown NJ.
Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome.
J Clin Endocrinol Metab.
2020 Jan 1;
105(1):.
Abstract: Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion.
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Disrupted Habituation in the Early Stage of Psychosis.
Biological psychiatry. Cognitive neuroscience and neuroimaging (2019)
Avery SN, McHugo M, Armstrong K, Blackford JU, Woodward ND, Heckers S.
Disrupted Habituation in the Early Stage of Psychosis.
Biol Psychiatry Cogn Neurosci Neuroimaging.
2019 Nov;
4(11):1004-1012.
Abstract: Learning and memory are impaired in schizophrenia. Some theories have proposed that one form of memory, habituation, is particularly impaired. Preliminary evidence suggests that memory impairment is associated with failed hippocampal habituation in patients with chronic schizophrenia. We studied how abnormal habituation of the hippocampus is related to relational memory deficits in the early stage of psychosis.
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Brain function during stages of working memory in schizophrenia and psychotic bipolar disorder.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2019)
Huang AS, Rogers BP, Anticevic A, Blackford JU, Heckers S, Woodward ND.
Brain function during stages of working memory in schizophrenia and psychotic bipolar disorder.
Neuropsychopharmacology.
2019 Nov;
44(12):2136-2142.
Abstract: Working memory (WM) is impaired in psychotic disorders and linked to functional outcome. Most neurobiological models emphasize prefrontal cortex (PFC) dysfunction in the etiology of WM impairment. However, WM is composed of multiple processes, including encoding and maintenance, and the delineation of the neurobiology of these sub-processes has not been well characterized in schizophrenia and psychotic bipolar disorder. Functional MRI was obtained during an event-related spatial delayed match-to-sample task from 58 healthy individuals, 72 individuals with schizophrenia and 41 people with bipolar I disorder with psychotic features in order to: 1) characterize neural responses during encoding, maintenance and retrieval stages of WM using complementary region-of-interest and whole brain approaches; 2) determine whether schizophrenia and psychotic bipolar disorder exhibit similar abnormalities in WM-related brain function; and 3) elucidate the associations between WM-related brain function, task performance, and neuropsychological functioning. Both schizophrenia and psychotic bipolar disorder groups showed encoding- and maintenance-related impairments in the posterior parietal cortex (PPC) and frontal eye fields (FEF). BOLD response in the PPC and FEF, during encoding and maintenance respectively, was associated with task performance independent of group. Additionally, encoding-related activation in the PPC correlated with general neuropsychological functioning independent of group. Only encoding-related activation in the right ventral striatum differed between schizophrenia and psychotic bipolar disorder; individuals with schizophrenia showed significantly lower activation than both psychotic bipolar disorder and healthy groups. Our results are consistent with emerging evidence implicating PPC dysfunction in WM impairment and suggest interventions targeting neural activation in PPC may improve WM and neuropsychological functioning across psychotic disorders.
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Frailty Is Related to Subjective Cognitive Decline in Older Women without Dementia.
Journal of the American Geriatrics Society (2019)
Gifford KA, Bell SP, Liu D, Neal JE, Turchan M, Shah AS, Jefferson AL.
Frailty Is Related to Subjective Cognitive Decline in Older Women without Dementia.
J Am Geriatr Soc.
2019 Sep;
67(9):1803-1811.
Abstract: Physical frailty (or loss of physiologic reserve) is associated with cognitive impairment and dementia. Subjective cognitive decline (SCD) may represent early pathologic changes of dementia. The association between these disease markers is unclear.
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Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.
Journal of autism and developmental disorders (2019)
Schroder CM, Malow BA, Maras A, Melmed RD, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P.
Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.
J Autism Dev Disord.
2019 Aug;
49(8):3218-3230.
Abstract: A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2-5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver's quality of life were evaluated. PedPRM treatment resulted in significant improvement in externalizing but not internalizing behavior (Strengths and Difficulties questionnaire; SDQ) compared to placebo (p = 0.021) with clinically-relevant improvements in 53.7% of PedPRM-treated versus 27.6% of placebo-treated subjects (p = 0.008). Caregivers' quality of life also improved with PedPRM versus placebo (p = 0.010) and correlated with the change in total SDQ (p = 0.0005). PedPRM alleviates insomnia-related difficulties, particularly externalizing behavior in the children, subsequently improving caregivers' quality of life.
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Lipoprotein modulation of proteinuric renal injury.
Laboratory investigation; a journal of technical methods and pathology (2019)
Tsuchida Y, Zhong J, Otsuka T, Dikalova A, Pastan I, Anantharamaiah GM, Linton MF, Yancey PG, Ikizler TA, Fogo AB, Yang H, Kon V.
Lipoprotein modulation of proteinuric renal injury.
Lab Invest.
2019 Jul;
99(8):1107-1116.
Abstract: High-density lipoprotein (HDL) and its main protein, apolipoprotein AI (apoAI), have established benefits in various cells, but whether these cytoprotective effects of HDL pertain to renal cells is unclear. We investigated the in vitro consequences of exposing damaged podocytes to normal apoAI, HDL, and apoAI mimetic (L-4F), and the in vivo effects of L-4F on kidney and atherosclerotic injury in a podocyte-specific injury model of proteinuria. In vitro, primary mouse podocytes were injured by puromycin aminonucleoside (PAN). Cellular viability, migration, production of reactive oxygen species (ROS), apoptosis, and the underlying signaling pathway were assessed. In vivo, we used a proteinuric model, Nphs1-hCD25 transgenic (NEP25) mice, which express human CD25 on podocytes. Podocyte injury was induced by using immunotoxin (LMB2) and generated a proteinuric atherosclerosis model, NEP25:apoE mice, was generated by mating apoE-deficient (apoE) mice with NEP25 mice. Animals received L-4F or control vehicle. Renal function, podocyte injury, and atherosclerosis were assessed. PAN reduced podocyte viability, migration, and increased ROS production, all significantly lessened by apoAI, HDL, and L-4F. L-4F attenuated podocyte apoptosis and diminished PAN-induced inactivation of Janus family protein kinase-2/signal transducers and activators of transcription 3. In NEP25 mice, L-4F significantly lessened overall proteinuria, and preserved podocyte expression of synaptopodin and cell density. Proteinuric NEP25:apoE mice had more atherosclerosis than non-proteinuric apoE mice, and these lesions were significantly decreased by L-4F. Normal human apoAI, HDL, and apoAI mimetic protect against podocyte damage. ApoAI mimetic provides in vivo beneficial effects on podocytes that culminate in reduced albuminuria and atherosclerosis. The results suggest supplemental apoAI/apoAI mimetic may be a novel candidate to lessen podocyte damage and its complications.
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Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age.
Human brain mapping (2019)
Seaman KL, Smith CT, Juarez EJ, Dang LC, Castrellon JJ, Burgess LL, San Juan MD, Kundzicz PM, Cowan RL, Zald DH, Samanez-Larkin GR.
Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age.
Hum Brain Mapp.
2019 Jul;
40(10):3125-3138.
Abstract: Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [ F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6-16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3-5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0-2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.
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Social and nonsocial reward moderate the relation between autism symptoms and loneliness in adults with ASD, depression, and controls.
Autism research : official journal of the International Society for Autism Research (2019)
Han GT, Tomarken AJ, Gotham KO.
Social and nonsocial reward moderate the relation between autism symptoms and loneliness in adults with ASD, depression, and controls.
Autism Res.
2019 Jun;
12(6):884-896.
Abstract: Individuals with autism spectrum disorder (ASD) report high levels of co-occurring mood disorders. Previous work suggests that people with ASD also experience aberrant responses to social reward compared to typically developing (TD) peers. In the TD population, aberrant reward processing has been linked to anhedonia (i.e., loss of pleasure), which is a hallmark feature of depression. This study examined the interplay between self-reported pleasure from social and nonsocial rewards, autism symptom severity, loneliness, and depressive symptoms across adults with autism spectrum disorder (ASD; N = 49), TD currently depressed adults (TD-dep; N = 30), and TD never depressed controls (TD-con; N = 28). The ASD cohort reported levels of social and nonsocial anhedonia that were greater than TD-con but not significantly different from TD-dep. Across cohorts, both social and nonsocial hedonic capacity moderated the relationship between autism symptoms and loneliness: individuals with low capacity for pleasure experienced elevated loneliness regardless of autism symptom severity, while those with intact capacity for pleasure (i.e., less anhedonia) experienced greater loneliness as a function of increased autism symptoms. Loneliness was the strongest predictor of depressive symptoms across clinical cohorts. Our findings suggest a putative pathway from trait-like anhedonia in ASD to depression via elevated loneliness and indicate that variability in hedonic capacity within the autism spectrum may differentially confer risk for depression in adults with ASD. Results underscore potential mental health benefits of social skills interventions and community inclusion programs for adults with ASD. Autism Res 2019, 12: 884-896. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The relationship between autism symptoms and loneliness depended on one's ability to experience both social and nonsocial pleasure. Adults who experienced less pleasure reported high levels of loneliness that did not depend autism severity, while adults with high capacity for pleasure were especially lonely if they also had many autism symptoms. Loneliness was the strongest predictor of depressive symptoms, compared to capacity for social and nonsocial pleasure and autism symptoms.
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Enhancing translational researchers' ability to collaborate with community stakeholders: Lessons from the Community Engagement Studio.
Journal of clinical and translational science (2018)
Joosten YA, Israel TL, Head A, Vaughn Y, Villalta Gil V, Mouton C, Wilkins CH.
Enhancing translational researchers' ability to collaborate with community stakeholders: Lessons from the Community Engagement Studio.
J Clin Transl Sci.
2018 Aug;
2(4):201-207.
Abstract: Community engagement is considered essential to effectively translate research into practice and is increasingly recognized as a key to successful clinical trial recruitment. Challenges to engaging community stakeholders in research persist and new methods are needed to facilitate meaningful stakeholder involvement. The Community Engagement Studio (CE Studio), a consultative model, has been used at every stage of the research process. Best practices drawn from the model could inform other methods of engagement. Using a mixed-methods approach that included evaluation surveys, impact surveys and interviews, we assessed the CE Studio program. We analyzed data from 75 CE Studios; 65 researchers and 591 community members completed surveys and 10 researchers completed interviews. Surveys indicate that 100% of researchers would request a CE Studio in the future, and 99.3% of community members would participate in a CE Studio again. We identified 6 practices to enhance community engagement in clinical and translational research: early input, researcher coaching, researcher humility, balancing power, neutral facilitator, and preparation of community stakeholders. These best practices may enhance the quality of existing community engagement approaches and improve the effectiveness of translational researchers' efforts to engage community stakeholders in their work.
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Perivascular spaces contribute to cognition beyond other small vessel disease markers.
Neurology (2019)
Passiak BS, Liu D, Kresge HA, Cambronero FE, Pechman KR, Osborn KE, Gifford KA, Hohman TJ, Schrag MS, Davis LT, Jefferson AL.
Perivascular spaces contribute to cognition beyond other small vessel disease markers.
Neurology.
2019 Mar 19;
92(12):e1309-e1321.
Abstract: To cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults.
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Characterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.
Clinical genetics (2019)
Peters SU, Fu C, Suter B, Marsh E, Benke TA, Skinner SA, Lieberman DN, Standridge S, Jones M, Beisang A, Feyma T, Heydeman P, Ryther R, Kaufmann WE, Glaze DG, Neul JL, Percy AK.
Characterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.
Clin Genet.
2019 May;
95(5):575-581.
Abstract: Individuals with methyl CpG binding protein 2 (MECP2) duplication syndrome (MDS) have varying degrees of severity in their mobility, hand use, developmental skills, and susceptibility to infections. In the present study, we examine the relationship between duplication size, gene content, and overall phenotype in MDS using a clinical severity scale. Other genes typically duplicated within Xq28 (eg, GDI1, RAB39B, FLNA) are associated with distinct clinical features independent of MECP2. We additionally compare the phenotype of this cohort (n = 48) to other reported cohorts with MDS. Utilizing existing indices of clinical severity in Rett syndrome, we found that larger duplication size correlates with higher severity in total clinical severity scores (r = 0.36; P = 0.02), and in total motor behavioral assessment inventory scores (r = 0.31; P = 0.05). Greater severity was associated with having the RAB39B gene duplicated, although most of these participants also had large duplications. Results suggest that developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism are common in MDS. This is the first study to show that duplication size is related to clinical severity. Future studies should examine whether large duplications which do not encompass RAB39B also contribute to clinical severity. Results also suggest the need for creating an MDS specific severity scale.
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Differences in the relation between temperament and vocabulary based on children's stuttering trajectories.
Journal of communication disorders (2019)
Singer CM, Walden TA, Jones RM.
Differences in the relation between temperament and vocabulary based on children's stuttering trajectories.
J Commun Disord.
2019 Mar - Apr;
78:57-68.
Abstract: The purpose of this study was to assess the relation between temperament and vocabulary development for children who stutter and persist, children who stutter and recover and children who do not stutter.
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Effect of competing noise on cortical auditory evoked potentials elicited by speech sounds in 7- to 25-year-old listeners.
Hearing research (2019)
Gustafson SJ, Billings CJ, Hornsby BWY, Key AP.
Effect of competing noise on cortical auditory evoked potentials elicited by speech sounds in 7- to 25-year-old listeners.
Hear Res.
2019 Mar 1;
373:103-112.
Abstract: Child listeners have particular difficulty with speech perception when competing speech noise is present; this challenge is often attributed to their immature top-down processing abilities. The purpose of this study was to determine if the effects of competing speech noise on speech-sound processing vary with age. Cortical auditory evoked potentials (CAEPs) were measured during an active speech-syllable discrimination task in 58 normal-hearing participants (age 7-25 years). Speech syllables were presented in quiet and embedded in competing speech noise (4-talker babble, +15 dB signal-to-noise ratio; SNR). While noise was expected to similarly reduce amplitude and delay latencies of N1 and P2 peaks in all listeners, it was hypothesized that effects of noise on the P3b peak would be inversely related to age due to the maturation of top-down processing abilities throughout childhood. Consistent with previous work, results showed that a +15 dB SNR reduces amplitudes and delays latencies of CAEPs for listeners of all ages, affecting speech-sound processing, delaying stimulus evaluation, and causing a reduction in behavioral speech-sound discrimination. Contrary to expectations, findings suggest that competing speech noise at a +15 dB SNR may have similar effects on various stages of speech-sound processing for listeners of all ages. Future research directions should examine how more difficult listening conditions (poorer SNRs) might affect results across ages.
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Self-reported cumulative medical opioid exposure and subjective responses on first use of opioids predict analgesic and subjective responses to placebo-controlled opioid administration.
Regional anesthesia and pain medicine (2019)
Bruehl S, Stone AL, Palmer C, Edwards DA, Buvanendran A, Gupta R, Chont M, Kennedy M, Burns JW.
Self-reported cumulative medical opioid exposure and subjective responses on first use of opioids predict analgesic and subjective responses to placebo-controlled opioid administration.
Reg Anesth Pain Med.
2019 Jan;
44(1):92-99.
Abstract: To expand the evidence base needed to enable personalized pain medicine, we evaluated whether self-reported cumulative exposure to medical opioids and subjective responses on first opioid use predicted responses to placebo-controlled opioid administration.
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The PathLink Acquired Gestational Tissue Bank: Feasibility of Project PLACENTA.
Journal of reproductive biotechnology & fertility (2018)
Linder JE, Batey K, Johnston R, Cohen EM, Wang Y, Wang X, Zaleski NM, Rogers LM, McDonald WH, Reyzer ML, Judd A, Goldstein J, Correa H, Pulley J, Aronoff DM.
The PathLink Acquired Gestational Tissue Bank: Feasibility of Project PLACENTA.
J Reprod Biotechnol Fertil.
2018;
7:14-27.
Abstract: The Vanderbilt Institute for Clinical and Translational Research piloted the development of Project PLACENTA (PathLink Acquired gEstatioNal Tissue bAnk). This project investigated the feasibility of a fresh gestational tissue biobank, which provides tissue linked to electronic medical records for investigators interested in maternal-fetal health.
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Human PAH is characterized by a pattern of lipid-related insulin resistance.
JCI insight (2019)
Hemnes AR, Luther JM, Rhodes CJ, Burgess JP, Carlson J, Fan R, Fessel JP, Fortune N, Gerszten RE, Halliday SJ, Hekmat R, Howard L, Newman JH, Niswender KD, Pugh ME, Robbins IM, Sheng Q, Shibao CA, Shyr Y, Sumner S, Talati M, Wharton J, Wilkins MR, Ye F, Y.
Human PAH is characterized by a pattern of lipid-related insulin resistance.
JCI Insight.
2019 Jan 10;
4(1):.
Abstract: Pulmonary arterial hypertension (PAH) is a deadly disease of the small pulmonary vasculature with an increased prevalence of insulin resistance (IR). Insulin regulates both glucose and lipid homeostasis. We sought to quantify glucose- and lipid-related IR in human PAH, testing the hypothesis that lipoprotein indices are more sensitive indices of IR in PAH.
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Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults.
The Journal of neuroscience : the official journal of the Society for Neuroscience (2019)
Castrellon JJ, Seaman KL, Crawford JL, Young JS, Smith CT, Dang LC, Hsu M, Cowan RL, Zald DH, Samanez-Larkin GR.
Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults.
J Neurosci.
2019 Jan 9;
39(2):321-332.
Abstract: Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: = 144 males and females across 3 samples) and one meta-analytic (Study 2: = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa. Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior.
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Reduced free-living activity levels in pulmonary arterial hypertension patients.
Pulmonary circulation (2019)
Halliday SJ, Shi H, Brittain EL, Hemnes AR.
Reduced free-living activity levels in pulmonary arterial hypertension patients.
Pulm Circ.
2019 Jan-Mar;
9(1):2045894018814182.
Abstract: We conducted a survey of pulmonary arterial hypertension (PAH) patients and healthy controls who use either a smartphone or wearable fitness device that tracks daily step count. We found that PAH patients have markedly reduced activity levels compared to controls, after controlling for confounders.
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A first investigation of tongue, lip, and jaw movements in persons with dysarthria due to multiple sclerosis.
Multiple sclerosis and related disorders (2019)
Mefferd AS, Lai A, Bagnato F.
A first investigation of tongue, lip, and jaw movements in persons with dysarthria due to multiple sclerosis.
Mult Scler Relat Disord.
2019 Jan;
27:188-194.
Abstract: Multiple sclerosis can affect the speech motor system and result in dysarthria.
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Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression.
Biological psychiatry. Cognitive neuroscience and neuroimaging (2019)
Gandelman JA, Albert K, Boyd BD, Park JW, Riddle M, Woodward ND, Kang H, Landman BA, Taylor WD.
Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression.
Biol Psychiatry Cogn Neurosci Neuroimaging.
2019 Feb;
4(2):160-170.
Abstract: Late-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology.
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Regionally specific volume deficits along the hippocampal long axis in early and chronic psychosis.
NeuroImage. Clinical (2018)
McHugo M, Talati P, Woodward ND, Armstrong K, Blackford JU, Heckers S.
Regionally specific volume deficits along the hippocampal long axis in early and chronic psychosis.
Neuroimage Clin.
2018;
20:1106-1114.
Abstract: Previous studies in psychosis patients have shown hippocampal volume deficits across anterior and posterior regions or across subfields, but subfield specific changes in volume along the hippocampal long axis have not been examined. Here, we tested the hypothesis that volume changes exist across the hippocampus in chronic psychosis but only the anterior CA region is affected in early psychosis patients. We analyzed structural MRI data from 179 patients with a non-affective psychotic disorder (94 chronic psychosis; 85 early psychosis) and 167 heathy individuals demographically matched to the chronic and early psychosis samples respectively (82 matched to chronic patients; 85 matched to early patients). We measured hippocampal volumes using Freesurfer 6-derived automated segmentation of both anterior and posterior regions and the CA, dentate gyrus, and subiculum subfields. We found a hippocampal volume deficit in both anterior and posterior regions in chronic psychosis, but this deficit was limited to the anterior hippocampus in early psychosis patients. This volume change was more pronounced in the anterior CA subfield of early psychosis patients than in the dentate gyrus or subiculum. Our findings support existing models of psychosis implicating initial CA dysfunction with later progression to other hippocampal regions and suggest that the anterior hippocampus may be an important target for early interventions.
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Development and Validation of the Lymphedema Symptom Intensity and Distress Survey-Lower Limb.
Lymphatic research and biology (2018)
Ridner SH, Doersam JK, Stolldorf DP, Dietrich MS.
Development and Validation of the Lymphedema Symptom Intensity and Distress Survey-Lower Limb.
Lymphat Res Biol.
2018 Dec;
16(6):538-546.
Abstract: Lymphedema is a chronic, incurable condition that occurs most commonly in lower limbs (legs and feet). Increased morbidity is seen with this form of lymphedema, but there are few studies and even fewer tools intended to assess symptom burden in patients impacted by this condition. A questionnaire, the Lymphedema Symptom Intensity and Distress Survey-Lower Limb (LSIDS-L), was developed to fill this gap. The measure is composed of several clusters of symptoms thought to characterize lower limb lymphedema. The initial work was conducted to propose and assess the face validity of the clusters. Subsequently, work was undertaken to empirically evaluate the presence of the symptom clusters, assess the reliability of the cluster scores, and evaluate the validity of the scores by studying associations with other valid measures.
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Posttraumatic stress disorder in interstitial cystitis/bladder pain syndrome: Relationship to patient phenotype and clinical practice implications.
Neurourology and urodynamics (2019)
McKernan LC, Johnson BN, Reynolds WS, Williams DA, Cheavens JS, Dmochowski RR, Crofford LJ.
Posttraumatic stress disorder in interstitial cystitis/bladder pain syndrome: Relationship to patient phenotype and clinical practice implications.
Neurourol Urodyn.
2019 Jan;
38(1):353-362.
Abstract: The relationship between exposure to abuse and interstitial cystitis/bladder pain syndrome (IC/BPS) is well-documented. However, studies have yet to examine posttraumatic stress disorder (PTSD), which develops following exposure to trauma and worsens health outcomes in chronic pain. We aimed to assess the prevalence and impact of PTSD in patients with IC/BPS, including their relation to genitourinary symptom presentation and widespread pain phenotype.
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Lack of consistent sex differences in D-amphetamine-induced dopamine release measured with [18F]fallypride PET.
Psychopharmacology (2019)
Smith CT, Dang LC, Burgess LL, Perkins SF, San Juan MD, Smith DK, Cowan RL, Le NT, Kessler RM, Samanez-Larkin GR, Zald DH.
Lack of consistent sex differences in D-amphetamine-induced dopamine release measured with [18F]fallypride PET.
Psychopharmacology (Berl).
2019 Feb;
236(2):581-590.
Abstract: Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed.
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Development of a method to maximize the transcutaneous electrical nerve stimulation intensity in women with fibromyalgia.
Journal of pain research (2018)
Vance CG, Chimenti RL, Dailey DL, Hadlandsmyth K, Zimmerman MB, Geasland KM, Williams JM, Merriwether EN, Alemo Munters L, Rakel BA, Crofford LJ, Sluka KA.
Development of a method to maximize the transcutaneous electrical nerve stimulation intensity in women with fibromyalgia.
J Pain Res.
2018;
11:2269-2278.
Abstract: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention clinically used for pain relief. The importance of utilizing the adequate stimulation intensity is well documented; however, clinical methods to achieve the highest possible intensity are not established.
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Body mass index and health-related quality of life.
Obesity science & practice (2018)
Apple R, Samuels LR, Fonnesbeck C, Schlundt D, Mulvaney S, Hargreaves M, Crenshaw D, Wallston KA, Heerman WJ.
Body mass index and health-related quality of life.
Obes Sci Pract.
2018 Oct;
4(5):417-426.
Abstract: There are conflicting data regarding the association between body mass index (BMI) and health-related quality of life (HRQoL), especially among certain population subgroups and for mental and physical health domains.
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Time of day effects on the relationship between daily sleep and anxiety: An ecological momentary assessment approach.
Behaviour research and therapy (2018)
Cox RC, Sterba SK, Cole DA, Upender RP, Olatunji BO.
Time of day effects on the relationship between daily sleep and anxiety: An ecological momentary assessment approach.
Behav Res Ther.
2018 Dec;
111:44-51.
Abstract: Previous research has linked sleep disturbance to anxiety. However, evidence for this relation has been inconsistent, largely limited to retrospective reports that do not account for daily variability, and silent on when the association is most pronounced. Thus, the present study utilized ecological momentary assessment (EMA) to examine the effects of daily deviations in total sleep time (TST) and person-average TST on anxiety and whether these effects varied as a function of time of day in a sample of unselected adults (N = 138). Results indicate that the amount of TST on a given night, relative to personal average TST, negatively predicted anxiety, and this relation was significant in the morning and afternoon, but not evening. In contrast, person-average TST was unrelated to average anxiety. Relations between TST and anxiety did not differ across objective (e.g., actigraphy) and subjective (e.g., sleep diary) measures. Furthermore, the pattern of results remained the same when controlling for previous day's anxiety and were not bidirectional. These findings suggest that getting less sleep than is typical for the individual predicts subsequent anxiety, and this effect is particularly strong in the morning. Average sleep duration may be less important to the experience of anxiety than deviations from that average. These findings highlight the importance of EMA to examine how and when variability in sleep confers vulnerability for anxiety symptoms.
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Audiovisual multisensory integration in individuals with autism spectrum disorder: A systematic review and meta-analysis.
Neuroscience and biobehavioral reviews (2018)
Feldman JI, Dunham K, Cassidy M, Wallace MT, Liu Y, Woynaroski TG.
Audiovisual multisensory integration in individuals with autism spectrum disorder: A systematic review and meta-analysis.
Neurosci Biobehav Rev.
2018 Dec;
95:220-234.
Abstract: An ever-growing literature has aimed to determine how individuals with autism spectrum disorder (ASD) differ from their typically developing (TD) peers on measures of multisensory integration (MSI) and to ascertain the degree to which differences in MSI are associated with the broad range of symptoms associated with ASD. Findings, however, have been highly variable across the studies carried out to date. The present work systematically reviews and quantitatively synthesizes the large literature on audiovisual MSI in individuals with ASD to evaluate the cumulative evidence for (a) group differences between individuals with ASD and TD peers, (b) correlations between MSI and autism symptoms in individuals with ASD and (c) study level factors that may moderate findings (i.e., explain differential effects) observed across studies. To identify eligible studies, a comprehensive search strategy was employed using the ProQuest search engine, PubMed database, forwards and backwards citation searches, direct author contact, and hand-searching of select conference proceedings. A significant between-group difference in MSI was evident in the literature, with individuals with ASD demonstrating worse audiovisual integration on average across studies compared to TD controls. This effect was moderated by mean participant age, such that between-group differences were more pronounced in younger samples. The mean correlation between MSI and autism and related symptomatology was also significant, indicating that increased audiovisual integration in individuals with ASD is associated with better language/communication abilities and/or reduced autism symptom severity in the extant literature. This effect was moderated by whether the stimuli were linguistic versus non-linguistic in nature, such that correlation magnitudes tended to be significantly greater when linguistic stimuli were utilized in the measure of MSI. Limitations and future directions for primary and meta-analytic research are discussed.
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In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2018)
Fuller JC Jr, Pitchford LM, Morrison RD, Daniels JS, Flynn CR, Abumrad NN, Oates JA, Boutaud O, Rathmacher JA.
In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate.
Food Chem Toxicol.
2018 Nov;
121:541-548.
Abstract: 2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA.
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Medial temporal lobe volumes in late-life depression: effects of age and vascular risk factors.
Brain imaging and behavior (2020)
Taylor WD, Deng Y, Boyd BD, Donahue MJ, Albert K, McHugo M, Gandelman JA, Landman BA.
Medial temporal lobe volumes in late-life depression: effects of age and vascular risk factors.
Brain Imaging Behav.
2020 Feb;
14(1):19-29.
Abstract: Substantial work associates late-life depression with hippocampal pathology. However, there is less information about differences in hippocampal subfields and other connected temporal lobe regions and how these regions may be influenced by vascular factors. Individuals aged 60 years or older with and without a DSM-IV diagnosis of Major Depressive Disorder completed clinical assessments and 3 T cranial MRI using a protocol allowing for automated measurement of medial temporal lobe subfield volumes. A subset also completed pseudo-continuous arterial spin labeling, allowing for the measurement of hippocampal cerebral blood flow. In 59 depressed and 21 never-depressed elders (mean age = 66.4 years, SD = 5.8y, range 60-86y), the depressed group did not exhibit statistically significant volumetric differences for the total hippocampus or hippocampal subfields but did exhibit significantly smaller volumes of the perirhinal cortex, specifically in the BA36 region. Additionally, age had a greater effect in the depressed group on volumes of the cornu ammonis, entorhinal cortex, and BA36 region. Finally, both clinical and radiological markers of vascular risk were associated with smaller BA36 volumes, while reduced hippocampal blood flow was associated with smaller hippocampal and cornu ammonis volumes. In conclusion, while we did not observe group differences in hippocampal regions, we observed group differences and an effect of vascular pathology on the BA36 region, part of the perirhinal cortex. This is a critical region exhibiting atrophy in prodromal Alzheimer's disease. Moreover, the observed greater effect of age in the depressed groups is concordant with past longitudinal studies reporting greater hippocampal atrophy in late-life depression.
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Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.
Multiple sclerosis (Houndmills, Basingstoke, England) (2019)
O'Grady KP, Dula AN, Lyttle BD, Thompson LM, Conrad BN, Box BA, McKeithan LJ, Pawate S, Bagnato F, Landman BA, Newhouse P, Smith SA.
Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.
Mult Scler.
2019 Oct;
25(12):1580-1592.
Abstract: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T- and T-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM.
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Therapeutic Applications of Nicotinic Stimulation: Successes, Failures, and Future Prospects.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2019)
Newhouse PA.
Therapeutic Applications of Nicotinic Stimulation: Successes, Failures, and Future Prospects.
Nicotine Tob Res.
2019 Feb 18;
21(3):345-348.
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Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression.
The Journal of clinical psychiatry (2018)
Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD.
Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression.
J Clin Psychiatry.
2018 Aug 28;
79(5):.
Abstract: Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms and cognitive performance in LLD.
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Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST).
Arthritis research & therapy (2018)
Merriwether EN, Frey-Law LA, Rakel BA, Zimmerman MB, Dailey DL, Vance CGT, Golchha M, Geasland KM, Chimenti R, Crofford LJ, Sluka KA.
Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST).
Arthritis Res Ther.
2018 Aug 29;
20(1):199.
Abstract: Although exercise is an effective treatment for fibromyalgia, the relationships between lifestyle physical activity and multiple symptomology domains of fibromyalgia are not clear. Thus, the purpose of this study was to comprehensively examine the relationships between lifestyle physical activity with multiple outcome domains in women with fibromyalgia, including pain, fatigue, function, pain-related psychological constructs, and quality of life.
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Differences in anticipatory versus reactive stress to social evaluative threat in adults versus adolescents with autism.
Autism research : official journal of the International Society for Autism Research (2018)
Taylor JL, Muscatello RA, Corbett BA.
Differences in anticipatory versus reactive stress to social evaluative threat in adults versus adolescents with autism.
Autism Res.
2018 Sep;
11(9):1276-1285.
Abstract: Social evaluative threat is a potent activator of the hypothalamic-pituitary-adrenocortical (HPA) axis in typically developing (TD) populations. Studies have shown that children and adolescents with autism spectrum disorder (ASD) show a blunted cortisol response to this type of stressor; yet, a previous study in adults with ASD reported a more prototypical stress response. The current study compared 24 adolescents and 17 adults with ASD to investigate a possible developmental lag in autism resulting in a more adaptive stress response to social evaluation with development. Participants were exposed to the trier social stress test (TSST), and salivary cortisol was collected before and after stress induction. Multilevel modeling revealed that relative to adolescents, young adults with ASD evidenced a significant increase in cortisol in response to anticipatory stress, and 23.5% were classified as anticipatory responders. Adolescents, however, had a significant change in slope in response to the TSST, with 37.5% classified as reactive responders. In both groups, the majority of participants did not have a robust stress response to the TSST as would be expected in TD participants. Findings suggest significant differences in the cortisol trajectory; adults with ASD were more likely to show an anticipatory response to being socially evaluated, which was maintained throughout the stressor, whereas the adolescents had a more reactive response pattern with no anticipatory response. Further research is needed to determine if such patterns are adaptive or deleterious, and to determine underlying factors that may contribute to distinct stress profiles and to the overall diminished stress responses. Autism Res 2018, 11: 1276-1285. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Many individuals have increased stress when being socially evaluated. The current study shows that adults with ASD have increased stress in anticipation of a task in which individuals are required to give a speech to unfamiliar raters, while adolescents with ASD tend to show a stress response only during the task itself. Further research is necessary to understand whether developmental influences on stress response in ASD have significant impacts on other areas of functioning often affected by stress.
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Impact of substance use disorder on gray matter volume in schizophrenia.
Psychiatry research. Neuroimaging (2018)
Quinn M, McHugo M, Armstrong K, Woodward N, Blackford J, Heckers S.
Impact of substance use disorder on gray matter volume in schizophrenia.
Psychiatry Res Neuroimaging.
2018 Oct 30;
280:9-14.
Abstract: Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects. Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history. Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history. Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.
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Pupil response to social-emotional material is associated with rumination and depressive symptoms in adults with autism spectrum disorder.
PloS one (2018)
Gotham KO, Siegle GJ, Han GT, Tomarken AJ, Crist RN, Simon DM, Bodfish JW.
Pupil response to social-emotional material is associated with rumination and depressive symptoms in adults with autism spectrum disorder.
PLoS One.
2018;
13(8):e0200340.
Abstract: Autism spectrum disorder (ASD) is marked by repetitive thinking and high rates of depression. Understanding the extent to which repetitive negative thinking in ASD reflects autistic stereotypy versus general depressive thinking patterns (e.g., rumination) could help guide treatment research to improve emotional health in ASD. We compared associations between rumination, depressive symptoms, and pupil response to social-emotional material in adults with ASD and typically developing (TD) adults with and without depression.
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Audiovisual Temporal Processing in Postlingually Deafened Adults with Cochlear Implants.
Scientific reports (2018)
Butera IM, Stevenson RA, Mangus BD, Woynaroski TG, Gifford RH, Wallace MT.
Audiovisual Temporal Processing in Postlingually Deafened Adults with Cochlear Implants.
Sci Rep.
2018 Jul 27;
8(1):11345.
Abstract: For many cochlear implant (CI) users, visual cues are vitally important for interpreting the impoverished auditory speech information that an implant conveys. Although the temporal relationship between auditory and visual stimuli is crucial for how this information is integrated, audiovisual temporal processing in CI users is poorly understood. In this study, we tested unisensory (auditory alone, visual alone) and multisensory (audiovisual) temporal processing in postlingually deafened CI users (n = 48) and normal-hearing controls (n = 54) using simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks. We varied the timing onsets between the auditory and visual components of either a syllable/viseme or a simple flash/beep pairing, and participants indicated either which stimulus appeared first (TOJ) or if the pair occurred simultaneously (SJ). Results indicate that temporal binding windows-the interval within which stimuli are likely to be perceptually 'bound'-are not significantly different between groups for either speech or non-speech stimuli. However, the point of subjective simultaneity for speech was less visually leading in CI users, who interestingly, also had improved visual-only TOJ thresholds. Further signal detection analysis suggests that this SJ shift may be due to greater visual bias within the CI group, perhaps reflecting heightened attentional allocation to visual cues.
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Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia.
Neurology (2018)
Jordan LC, Kassim AA, Donahue MJ, Juttukonda MR, Pruthi S, Davis LT, Rodeghier M, Lee CA, Patel NJ, DeBaun MR.
Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia.
Neurology.
2018 Aug 21;
91(8):e781-e784.
Abstract: Because of the high prevalence of silent cerebral infarcts (SCIs) in adults with sickle cell anemia (SCA) and lack of information to guide treatment strategies, we evaluated the risk of recurrent SCIs and overt stroke in adults with SCA with preexisting SCI.
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Toileting Behaviors of Women-What is Healthy?
The Journal of urology (2019)
Kowalik CG, Daily A, Delpe S, Kaufman MR, Fowke J, Dmochowski RR, Reynolds WS.
Toileting Behaviors of Women-What is Healthy?
J Urol.
2019 Jan;
201(1):129-134.
Abstract: The objective of this study was to assess toileting behaviors in community dwelling women.
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Neurofilament relates to white matter microstructure in older adults.
Neurobiology of aging (2018)
Moore EE, Hohman TJ, Badami FS, Pechman KR, Osborn KE, Acosta LMY, Bell SP, Babicz MA, Gifford KA, Anderson AW, Goldstein LE, Blennow K, Zetterberg H, Jefferson AL.
Neurofilament relates to white matter microstructure in older adults.
Neurobiol Aging.
2018 Oct;
70:233-241.
Abstract: Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-β-negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.
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Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.
Circulation (2018)
Jefferson AL, Cambronero FE, Liu D, Moore EE, Neal JE, Terry JG, Nair S, Pechman KR, Rane S, Davis LT, Gifford KA, Hohman TJ, Bell SP, Wang TJ, Beckman JA, Carr JJ.
Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.
Circulation.
2018 Oct 30;
138(18):1951-1962.
Abstract: Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults.
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DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition.
Hypertension (Dallas, Tex. : 1979) (2018)
Hubers SA, Wilson JR, Yu C, Nian H, Grouzmann E, Eugster P, Shibao CA, Billings FT 4th, Jafarian Kerman S, Brown NJ.
DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition.
Hypertension.
2018 Sep;
72(3):712-719.
Abstract: DPP (dipeptidyl peptidase)-4 inhibitors are antidiabetic drugs that may increase heart failure in high-risk patients. NPY (neuropeptide Y) is coreleased with norepinephrine, causes vasoconstriction via the Y1 receptor, and is degraded by DPP4 to NPY (3-36) in vitro. NPY (3-36) decreases release of norepinephrine via the Y2 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the vasoconstrictor effect of NPY. Eighteen nonsmokers (12 healthy controls and 6 with type 2 diabetes mellitus) participated in 1 of 2 randomized, double-blind, placebo-controlled crossover studies. First, subjects were randomized to order of treatment with sitagliptin 100 mg/d versus placebo for 7 days separated by 4-week washout. On the last day of treatment, NPY was infused by brachial artery and forearm blood flow was measured using plethysmography. Blood samples were collected after each dose. NPY infusions were repeated after 90-minute washout and intra-arterial enalaprilat. Second, 5 healthy subjects were randomized to crossover treatment with sitagliptin 100 mg/d plus valsartan 160 mg/d versus placebo plus valsartan. NPY infusions were performed on the seventh day of treatment. NPY caused dose-dependent vasoconstriction. During enalaprilat, sitagliptin significantly potentiated NPY-induced vasoconstriction in controls and diabetics ( P≤0.02 for forearm blood flow in either group). Baseline norepinephrine release was increased during sitagliptin and enalaprilat, but not further by NPY. Sitagliptin increased the ratio of NPY to NPY (3-36). During valsartan, sitagliptin also significantly potentiated NPY-induced vasoconstriction ( P=0.009 for forearm blood flow). Potentiation of endogenous NPY could contribute to cardiovascular effects of DPP4 inhibitors in patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
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Impaired associative inference in the early stage of psychosis.
Schizophrenia research (2018)
Armstrong K, Avery S, Blackford JU, Woodward N, Heckers S.
Impaired associative inference in the early stage of psychosis.
Schizophr Res.
2018 Dec;
202:86-90.
Abstract: Relational memory is impaired in chronic schizophrenia. It is unclear if similar deficits are already present in the early stage of psychosis. We used the Associative Inference Paradigm to test relational memory ability in the early stage of a non-affective psychotic disorder. Eighty-two early stage psychosis patients and 67 healthy control subjects were trained on 3 sets of 30 paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), F3-F4 (two new faces). Subjects who reached 80% recall accuracy of the paired associates during training were then tested for their ability to recall the previously seen pairs and solve a novel, inferential pairing F1-F2 (faces linked through association to same house). Sixty early psychosis patients (73%) and 67 healthy control subjects (100%) successfully reached the accuracy threshold (80%) during training and were included in the analysis of relational memory. The early stage psychosis patients showed less of an associative inference effect than the healthy controls (pair type by group interaction: F (1,125) = 5.04, p < 0.05). However, the majority of early psychosis patients (52%) displayed intact inferential memory, compared to our prior study which revealed just 16% of chronic schizophrenia patients had intact inferential memory. Patients in the early stage of psychosis show a relational memory deficit, although less pronounced than in chronic schizophrenia. Longitudinal studies are needed to examine the progression of relational memory deficits in schizophrenia and its associations with clinical, functional, and biological measures.
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Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults.
Journal of the American Heart Association (2018)
Moore EE, Liu D, Pechman KR, Terry JG, Nair S, Cambronero FE, Bell SP, Gifford KA, Anderson AW, Hohman TJ, Carr JJ, Jefferson AL.
Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults.
J Am Heart Assoc.
2018 Jun 26;
7(13):.
Abstract: Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment.
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Improved Stability of Whole Brain Surface Parcellation with Multi-Atlas Segmentation.
Proceedings of SPIE--the International Society for Optical Engineering (2018)
Huo Y, Bao S, Parvathaneni P, Landman BA.
Improved Stability of Whole Brain Surface Parcellation with Multi-Atlas Segmentation.
Proc SPIE Int Soc Opt Eng.
2018 Mar;
10574:.
Abstract: Whole brain segmentation and cortical surface parcellation are essential in understanding the brain anatomical-functional relationship. Multi-atlas segmentation has been regarded as one of the leading segmentation methods for the whole brain segmentation. In our recent work, the multi-atlas technique has been adapted to surface reconstruction using a method called Multi-atlas CRUISE (MaCRUISE). The MaCRUISE method not only performed the consistent volume-surface analyses but also shown advantages on robustness compared with FreeSurfer method. However, a detailed surface parcellation was not provided by MaCRUISE, which hindered the region of interests (ROI) based analyses on surfaces. Herein, the MaCRUISE surface parcellation (MaCRUISEsp) method is proposed to perform the surface parcellation upon the inner, central and outer surfaces that are reconstructed from MaCRUISE. MaCRUISEsp parcellates inner, central and outer surfaces with 98 cortical labels respectively using a volume segmentation based surface parcellation (VSBSP), following a topological correction step. To validate the performance of MaCRUISEsp, 21 scan-rescan magnetic resonance imaging (MRI) T1 volume pairs from the Kirby21 dataset were used to perform a reproducibility analyses. MaCRUISEsp achieved 0.948 on median Dice Similarity Coefficient (DSC) for central surfaces. Meanwhile, FreeSurfer achieved 0.905 DSC for inner surfaces and 0.881 DSC for outer surfaces, while the proposed method achieved 0.929 DSC for inner surfaces and 0.835 DSC for outer surfaces. Qualitatively, the results are encouraging, but are not directly comparable as the two approaches use different definitions of cortical labels.
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High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial.
American heart journal (2018)
Vardeny O, Udell JA, Joseph J, Farkouh ME, Hernandez AF, McGeer AJ, Talbot HK, Bhatt DL, Cannon CP, Goodman SG, Anand I, DeMets DL, Temte J, Wittes J, Nichol K, Yancy CW, Gaziano JM, Cooper LS, Kim K, Solomon SD.
High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial.
Am Heart J.
2018 Aug;
202:97-103.
Abstract: Influenza leads to significant cardiopulmonary morbidity and mortality-particularly in patients with cardiovascular disease-that may be prevented with a standard influenza vaccine. However, patients with cardiovascular conditions have a reduced immune response to influenza vaccine, potentially resulting in reduced effectiveness for preventing clinical events. High-dose vaccine augments immune response in cardiac patients, suggesting that a high-dose influenza vaccination strategy may further reduce morbidity and mortality. Alternatively, broader coverage with an influenza vaccine containing an increased number of viral strains is an alternative strategy without direct evaluation.
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Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause.
Psycho-oncology (2018)
Vega JN, Dumas J, Newhouse PA.
Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause.
Psychooncology.
2018 Sep;
27(9):2198-2205.
Abstract: Cancer-related cognitive impairment (CRCI) is commonly reported following the administration of cancer treatment. Current longitudinal studies, primarily in women with breast cancer, suggest that up to 35% to 60% of patients exhibit persistent CRCI (pCRCI) following completion of chemotherapy. Complaints of subjective cognitive decline (SCD) are also commonly reported by women during and following the menopause transition in noncancer patients. Although the majority of evidence for cognitive difficulties in cancer patients and survivors is attributed to chemotherapy, there is growing evidence to suggest that menopausal status can also influence cognitive function in cancer patients.
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Brain basis of cognitive resilience: Prefrontal cortex predicts better reading comprehension in relation to decoding.
PloS one (2018)
Patael SZ, Farris EA, Black JM, Hancock R, Gabrieli JDE, Cutting LE, Hoeft F.
Brain basis of cognitive resilience: Prefrontal cortex predicts better reading comprehension in relation to decoding.
PLoS One.
2018;
13(6):e0198791.
Abstract: The ultimate goal of reading is to understand written text. To accomplish this, children must first master decoding, the ability to translate printed words into sounds. Although decoding and reading comprehension are highly interdependent, some children struggle to decode but comprehend well, whereas others with good decoding skills fail to comprehend. The neural basis underlying individual differences in this discrepancy between decoding and comprehension abilities is virtually unknown.
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Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.
American journal of physiology. Endocrinology and metabolism (2018)
Deger SM, Hewlett JR, Gamboa J, Ellis CD, Hung AM, Siew ED, Mamnungu C, Sha F, Bian A, Stewart TG, Abumrad NN, Ikizler TA.
Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.
Am J Physiol Endocrinol Metab.
2018 Dec 1;
315(6):E1108-E1120.
Abstract: Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB), and SM protein turnover in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic-euglycemic-euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual clamp, controls had a higher increase in WB protein synthesis and a higher suppression of WB protein breakdown compared with MHD patients, resulting in statistically significantly more positive WB protein net balance [2.02 (interquartile range [IQR]: 1.79 and 2.36) vs. 1.68 (IQR: 1.46 and 1.91) mg·kg fat-free mass·min for controls vs. for MHD patients, respectively, P < 0.001]. At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls, but SM net protein balance was similar between groups. During dual clamp, SM protein synthesis increased statistically significantly more in controls compared with MHD patients ( P = 0.03), whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared with MHD patients [67.3 (IQR: 46.4 and 97.1) vs. 15.4 (IQR: -83.7 and 64.7) μg·100 ml·min for controls and MHD patients, respectively, P = 0.03]. Human SM biopsy showed a positive correlation between glucose and leucine disposal rates, phosphorylated AKT to AKT ratio, and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients.
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Adults with Autism and Adults with Depression Show Similar Attentional Biases to Social-Affective Images.
Journal of autism and developmental disorders (2020)
Unruh KE, Bodfish JW, Gotham KO.
Adults with Autism and Adults with Depression Show Similar Attentional Biases to Social-Affective Images.
J Autism Dev Disord.
2020 Jul;
50(7):2336-2347.
Abstract: Individuals with ASD have increased rates of depression compared to the general population. Repetitive cognition is a core feature of ASD; in typically developing adults, repetitive cognition has been associated with attentional biases to negative emotional material and increased prospective depression risk. We compared adults with ASD to typically developing adults with depression and never-depressed controls, using a paired preference paradigm sensitive to affective biases in the context of repetitive cognition. Both clinical cohorts oriented faster to negative social-emotional material and spent less time overall on positive material, compared to healthy controls. Exploratory analyses within ASD revealed specific influences of repetitive behavior on patterns of affective bias. Findings help pinpoint susceptibilities in ASD that may confer increased risk for depression.
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Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy.
Journal of acquired immune deficiency syndromes (1999) (2018)
Koethe JR, Jenkins CA, Furch BD, Lake JE, Barnett L, Hager CC, Smith R, Hulgan T, Shepherd BE, Kalams SA.
Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy.
J Acquir Immune Defic Syndr.
2018 Sep 1;
79(1):135-140.
Abstract: Obesity alters adipose tissue immunology, and these changes may be reflected in circulating soluble inflammatory biomarker and T-cell subset profiles measured in HIV research studies.
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B-Type Natriuretic Peptide Levels and Mortality in Patients With and Without Heart Failure.
Journal of the American College of Cardiology (2018)
York MK, Gupta DK, Reynolds CF, Farber-Eger E, Wells QS, Bachmann KN, Xu M, Harrell FE Jr, Wang TJ.
B-Type Natriuretic Peptide Levels and Mortality in Patients With and Without Heart Failure.
J Am Coll Cardiol.
2018 May 15;
71(19):2079-2088.
Abstract: Circulating B-type natriuretic peptide (BNP) concentrations strongly predict mortality in patients with heart failure (HF). Both cardiac and extracardiac stimuli influence BNP levels, suggesting that BNP might have similar prognostic value in patients without HF.
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Towards Portable Large-Scale Image Processing with High-Performance Computing.
Journal of digital imaging (2018)
Huo Y, Blaber J, Damon SM, Boyd BD, Bao S, Parvathaneni P, Noguera CB, Chaganti S, Nath V, Greer JM, Lyu I, French WR, Newton AT, Rogers BP, Landman BA.
Towards Portable Large-Scale Image Processing with High-Performance Computing.
J Digit Imaging.
2018 Jun;
31(3):304-314.
Abstract: High-throughput, large-scale medical image computing demands tight integration of high-performance computing (HPC) infrastructure for data storage, job distribution, and image processing. The Vanderbilt University Institute for Imaging Science (VUIIS) Center for Computational Imaging (CCI) has constructed a large-scale image storage and processing infrastructure that is composed of (1) a large-scale image database using the eXtensible Neuroimaging Archive Toolkit (XNAT), (2) a content-aware job scheduling platform using the Distributed Automation for XNAT pipeline automation tool (DAX), and (3) a wide variety of encapsulated image processing pipelines called "spiders." The VUIIS CCI medical image data storage and processing infrastructure have housed and processed nearly half-million medical image volumes with Vanderbilt Advanced Computing Center for Research and Education (ACCRE), which is the HPC facility at the Vanderbilt University. The initial deployment was natively deployed (i.e., direct installations on a bare-metal server) within the ACCRE hardware and software environments, which lead to issues of portability and sustainability. First, it could be laborious to deploy the entire VUIIS CCI medical image data storage and processing infrastructure to another HPC center with varying hardware infrastructure, library availability, and software permission policies. Second, the spiders were not developed in an isolated manner, which has led to software dependency issues during system upgrades or remote software installation. To address such issues, herein, we describe recent innovations using containerization techniques with XNAT/DAX which are used to isolate the VUIIS CCI medical image data storage and processing infrastructure from the underlying hardware and software environments. The newly presented XNAT/DAX solution has the following new features: (1) multi-level portability from system level to the application level, (2) flexible and dynamic software development and expansion, and (3) scalable spider deployment compatible with HPC clusters and local workstations.
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Individual differences in dopamine D2 receptor availability correlate with reward valuation.
Cognitive, affective & behavioral neuroscience (2018)
Dang LC, Samanez-Larkin GR, Castrellon JJ, Perkins SF, Cowan RL, Zald DH.
Individual differences in dopamine D2 receptor availability correlate with reward valuation.
Cogn Affect Behav Neurosci.
2018 Aug;
18(4):739-747.
Abstract: Reward valuation, which underlies all value-based decision-making, has been associated with dopamine function in many studies of nonhuman animals, but there is relatively less direct evidence for an association in humans. Here, we measured dopamine D receptor (DRD2) availability in vivo in humans to examine relations between individual differences in dopamine receptor availability and neural activity associated with a measure of reward valuation, expected value (i.e., the product of reward magnitude and the probability of obtaining the reward). Fourteen healthy adult subjects underwent PET with [F]fallypride, a radiotracer with strong affinity for DRD2, and fMRI (on a separate day) while performing a reward valuation task. [F]fallypride binding potential, reflecting DRD2 availability, in the midbrain correlated positively with neural activity associated with expected value, specifically in the left ventral striatum/caudate. The present results provide in vivo evidence from humans showing midbrain dopamine characteristics are associated with reward valuation.
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Cortical associates of emotional reactivity and regulation in childhood stuttering.
Journal of fluency disorders (2018)
Zengin-Bolatkale H, Conture EG, Key AP, Walden TA, Jones RM.
Cortical associates of emotional reactivity and regulation in childhood stuttering.
J Fluency Disord.
2018 Jun;
56:81-99.
Abstract: This study sought to determine the cortical associates of emotional reactivity and emotion regulation (as indexed by the amplitude of evoked response potentials [ERP]) in young children who do and do not stutter during passive viewing of pleasant, unpleasant and neutral pictures.
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Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities.
Neurobiology of aging (2018)
Osborn KE, Liu D, Samuels LR, Moore EE, Cambronero FE, Acosta LMY, Bell SP, Babicz MA, Gordon EA, Pechman KR, Davis LT, Gifford KA, Hohman TJ, Blennow K, Zetterberg H, Jefferson AL.
Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities.
Neurobiol Aging.
2018 Aug;
68:18-25.
Abstract: White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid deposition (Aβ), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ (β = -0.001, p = 0.007) and NFL (β = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.
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Validating parent and child forms of the Parent Perception Inventory.
Psychological assessment (2018)
Cole DA, Goodman SH, Garber J, Cullum KA, Cho SJ, Rights JD, Felton JW, Jacquez FM, Korelitz KE, Simon HFM.
Validating parent and child forms of the Parent Perception Inventory.
Psychol Assess.
2018 Aug;
30(8):1065-1081.
Abstract: Understanding parenting from both parent and child perspectives is critical to child clinical and developmental research. Similarities and differences between parents' and children's reports can be highly informative, but only if they derive from psychometrically sound measures that assess the same parenting constructs. We examined the psychometric properties of the child and parent forms of the Parenting Perception Inventory (Bruce et al., 2006), which measures perceptions of two higher-order dimensions: positive, warm, supportive parenting; and negative, harsh, critical parenting. Data from a four-wave, longitudinal study of community children and adolescents (n = 876, Mage = 9.5 at the beginning), and data from a study of children (n = 131, Mage = 9.35) of depressed and nondepressed mothers provided psychometric support for both measures. Factor analyses revealed the existence of two factors in both the child and parent forms, and showed strong congruence across the two forms. Other analyses examined longitudinal structure, item difficulty, item discriminations, and scale coverage of the child form. Parents' and children's perceptions of parenting were related to children's affect, emotionality, and depressive symptoms. Parents' perceptions of parenting were related to parents' depressive symptoms and to parenting self-efficacy. (PsycINFO Database Record
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The role of eveningness in obsessive-compulsive symptoms: Cross-sectional and prospective approaches.
Journal of affective disorders (2018)
Cox RC, Tuck B, Olatunji BO.
The role of eveningness in obsessive-compulsive symptoms: Cross-sectional and prospective approaches.
J Affect Disord.
2018 Aug 1;
235:448-455.
Abstract: Eveningness may be defined as the tendency to be most active and alert during the evening. Previous research has linked eveningness with maladaptive psychological outcomes, and recent evidence has highlighted circadian dysregulation as a novel factor in psychopathology, including obsessive-compulsive disorder (OCD). However, limited research has examined the unique relationship between eveningness and OC symptoms. Two studies were conducted to thoroughly examine the links between eveningness and OC symptoms, while also considering the role of depression symptoms and sleep-related factors.
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Absence of Fibrosis and Inflammation by Cardiac Magnetic Resonance Imaging in Rheumatoid Arthritis Patients with Low to Moderate Disease Activity.
The Journal of rheumatology (2018)
Bradham W, Ormseth MJ, Elumogo C, Palanisamy S, Liu CY, Lawson MA, Soslow JH, Kawel-Boehm N, Bluemke DA, Stein CM.
Absence of Fibrosis and Inflammation by Cardiac Magnetic Resonance Imaging in Rheumatoid Arthritis Patients with Low to Moderate Disease Activity.
J Rheumatol.
2018 Aug;
45(8):1078-1084.
Abstract: The prevalence of heart failure is increased 2-fold in patients with rheumatoid arthritis (RA); this is not explained by ischemic heart disease or other risk factors for heart failure. We hypothesized that in patients with RA without known heart disease, cardiac magnetic resonance imaging (cMRI) would detect altered cardiac structure, function, and fibrosis.
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APOE genotype modifies the association between central arterial stiffening and cognition in older adults.
Neurobiology of aging (2018)
Cambronero FE, Liu D, Neal JE, Moore EE, Gifford KA, Terry JG, Nair S, Pechman KR, Osborn KE, Hohman TJ, Bell SP, Sweatt JD, Wang TJ, Beckman JA, Carr JJ, Jefferson AL.
APOE genotype modifies the association between central arterial stiffening and cognition in older adults.
Neurobiol Aging.
2018 Jul;
67:120-127.
Abstract: Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (β = -0.29, p = 0.01), executive function (β = -0.44, p = 0.02), and episodic memory (β = -3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.
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Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.
Biological psychiatry. Cognitive neuroscience and neuroimaging (2018)
Avery SN, Rogers BP, Heckers S.
Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.
Biol Psychiatry Cogn Neurosci Neuroimaging.
2018 May;
3(5):423-432.
Abstract: Functional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision.
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Cognitive performance in antidepressant-free recurrent major depressive disorder.
Depression and anxiety (2018)
Albert KM, Potter GG, McQuoid DR, Taylor WD.
Cognitive performance in antidepressant-free recurrent major depressive disorder.
Depress Anxiety.
2018 Aug;
35(8):694-699.
Abstract: Cognitive complaints are common in depression, and cognition may be an important treatment target as cognitive problems often remain during remission and may contribute to recurrence risk. Previous studies of cognitive performance in depression have mainly examined late-life depression, with a focus on older adults, or assessed performance in specific cognitive tasks rather than cognitive domains.
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Subjective value representations during effort, probability and time discounting across adulthood.
Social cognitive and affective neuroscience (2018)
Seaman KL, Brooks N, Karrer TM, Castrellon JJ, Perkins SF, Dang LC, Hsu M, Zald DH, Samanez-Larkin GR.
Subjective value representations during effort, probability and time discounting across adulthood.
Soc Cogn Affect Neurosci.
2018 May 1;
13(5):449-459.
Abstract: Every day, humans make countless decisions that require the integration of information about potential benefits (i.e. rewards) with other decision features (i.e. effort required, probability of an outcome or time delays). Here, we examine the overlap and dissociation of behavioral preferences and neural representations of subjective value in the context of three different decision features (physical effort, probability and time delays) in a healthy adult life span sample. While undergoing functional neuroimaging, participants (N = 75) made incentive compatible choices between a smaller monetary reward with lower physical effort, higher probability, or a shorter time delay versus a larger monetary reward with higher physical effort, lower probability, or a longer time delay. Behavioral preferences were estimated from observed choices, and subjective values were computed using individual hyperbolic discount functions. We found that discount rates were uncorrelated across tasks. Despite this apparent behavioral dissociation between preferences, we found overlapping subjective value-related activity in the medial prefrontal cortex across all three tasks. We found no consistent evidence for age differences in either preferences or the neural representations of subjective value across adulthood. These results suggest that while the tolerance of decision features is behaviorally dissociable, subjective value signals share a common representation across adulthood.
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Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.
AIDS research and human retroviruses (2018)
Bailin SS, Jenkins CA, Petucci C, Culver JA, Shepherd BE, Fessel JP, Hulgan T, Koethe JR.
Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.
AIDS Res Hum Retroviruses.
2018 Jun;
34(6):536-543.
Abstract: In human immunodeficiency virus (HIV)-negative individuals, a plasma metabolite profile, characterized by higher levels of branched-chain amino acids (BCAA), aromatic amino acids, and C3/C5 acylcarnitines, is associated with insulin resistance and increased risk of diabetes. We sought to characterize the metabolite profile accompanying insulin resistance in HIV-positive persons to assess whether the same or different bioenergetics pathways might be implicated. We performed an observational cohort study of 70 nondiabetic, HIV-positive individuals (50% with body mass index ≥30 kg/m) on efavirenz, tenofovir, and emtricitabine with suppressed HIV-1 RNA levels (<50 copies/mL) for at least 2 years and a CD4 count over 350 cells/μL. We measured fasting insulin resistance using the homeostatic model assessment 2, plasma free fatty acids (FFA) using gas chromatography, and amino acids, acylcarnitines, and organic acids using liquid chromatography/mass spectrometry. We assessed the relationship of plasma metabolites with insulin resistance using multivariable linear regression. The median age was 45 years, median CD4 count was 701 cells/μL, and median hemoglobin A1c was 5.2%. Insulin resistance was associated with higher plasma C3 acylcarnitines (p = .01), but not BCAA or C5 acylcarnitines. However, insulin resistance was associated with lower plasma levels of C18, C16, C12, and C2 acylcarnitines (p ≤ .03 for all), and lower C18 and C16 acylcarnitine:FFA ratios (p = .002, and p = .03, respectively). In HIV-positive persons, lower levels of plasma acylcarnitines, including the C2 product of complete fatty acid oxidation, are a more prominent feature of insulin resistance than changes in BCAA, suggesting impaired fatty acid uptake and/or mitochondrial oxidation is a central aspect of glucose intolerance in this population.
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Atypical audiovisual temporal function in autism and schizophrenia: similar phenotype, different cause.
The European journal of neuroscience (2018)
Noel JP, Stevenson RA, Wallace MT.
Atypical audiovisual temporal function in autism and schizophrenia: similar phenotype, different cause.
Eur J Neurosci.
2018 May;
47(10):1230-1241.
Abstract: Binding across sensory modalities yields substantial perceptual benefits, including enhanced speech intelligibility. The coincidence of sensory inputs across time is a fundamental cue for this integration process. Recent work has suggested that individuals with diagnoses of schizophrenia (SZ) and autism spectrum disorder (ASD) will characterize auditory and visual events as synchronous over larger temporal disparities than their neurotypical counterparts. Namely, these clinical populations possess an enlarged temporal binding window (TBW). Although patients with SZ and ASD share aspects of their symptomatology, phenotypic similarities may result from distinct etiologies. To examine similarities and variances in audiovisual temporal function in these two populations, individuals diagnosed with ASD (n = 46; controls n = 40) and SZ (n = 16, controls = 16) completed an audiovisual simultaneity judgment task. In addition to standard psychometric analyses, synchrony judgments were assessed using Bayesian causal inference modeling. This approach permits distinguishing between distinct causes of an enlarged TBW: an a priori bias to bind sensory information and poor fidelity in the sensory representation. Findings indicate that both ASD and SZ populations show deficits in multisensory temporal acuity. Importantly, results suggest that while the wider TBWs in ASD most prominently results from atypical priors, the wider TBWs in SZ results from a trend toward changes in prior and weaknesses in the sensory representations. Results are discussed in light of current ASD and SZ theories and highlight that different perceptual training paradigms focused on improving multisensory integration may be most effective in these two clinical populations and emphasize that similar phenotypes may emanate from distinct mechanistic causes.
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Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society (2018)
Mehr SE, Barbul A, Shibao CA.
Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review.
Clin Auton Res.
2018 Aug;
28(4):411-421.
Abstract: Gastrointestinal symptoms are among the most common complaints in patients with postural tachycardia syndrome (POTS). In some cases, they dominate the clinical presentation and cause substantial disabilities, including significant weight loss and malnutrition, that require the use of invasive treatment to support caloric intake. Multiple cross-sectional studies have reported a high prevalence of gastrointestinal symptoms in POTS patients with connective tissue diseases, such as Ehlers-Danlos, hypermobile type, and in patients with evidence of autonomic neuropathy. Previous studies that evaluated gastric motility in these patients reported a wide range of abnormalities, particularly delayed gastric emptying. The pathophysiology of gastrointestinal symptoms in POTS is likely multifactorial and probably depends on the co-morbid conditions. In patients with POTS and Ehlers-Danlos syndromes, structural and functional abnormalities in the gastrointestinal connective tissue may play a significant role, whereas in neuropathic POTS, the gastrointestinal tract motility and gut hormonal secretion may be directly impaired due to localized autonomic denervation. In patients with normal gastrointestinal motility but persistent gastrointestinal symptoms, gastrointestinal functional disorders should be considered. We performed a systematic review of the literature related to POTS and gastrointestinal symptoms have proposed possible mechanisms and discussed diagnosis and treatment approaches for delayed gastric emptying, the most common gastrointestinal abnormality reported in patients with POTS.
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Assessment of Plasma Proteomics Biomarker's Ability to Distinguish Benign From Malignant Lung Nodules: Results of the PANOPTIC (Pulmonary Nodule Plasma Proteomic Classifier) Trial.
Chest (2018)
Silvestri GA, Tanner NT, Kearney P, Vachani A, Massion PP, Porter A, Springmeyer SC, Fang KC, Midthun D, Mazzone PJ, PANOPTIC Trial Team..
Assessment of Plasma Proteomics Biomarker's Ability to Distinguish Benign From Malignant Lung Nodules: Results of the PANOPTIC (Pulmonary Nodule Plasma Proteomic Classifier) Trial.
Chest.
2018 Sep;
154(3):491-500.
Abstract: Lung nodules are a diagnostic challenge, with an estimated yearly incidence of 1.6 million in the United States. This study evaluated the accuracy of an integrated proteomic classifier in identifying benign nodules in patients with a pretest probability of cancer (pCA) ≤ 50%.
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Reverberation enhances onset dominance in sound localization.
The Journal of the Acoustical Society of America (2018)
Stecker GC, Moore TM.
Reverberation enhances onset dominance in sound localization.
J Acoust Soc Am.
2018 Feb;
143(2):786.
Abstract: Temporal variation in sensitivity to sound-localization cues was measured in anechoic conditions and in simulated reverberation using the temporal weighting function (TWF) paradigm [Stecker and Hafter (2002). J. Acoust. Soc. Am. 112, 1046-1057]. Listeners judged the locations of Gabor click trains (4 kHz center frequency, 5-ms interclick interval) presented from an array of loudspeakers spanning 360° azimuth. Targets ranged ±56.25° across trials. Individual clicks within each train varied by an additional ±11.25° to allow TWF calculation by multiple regression. In separate conditions, sounds were presented directly or in the presence of simulated reverberation: 13 orders of lateral reflection were computed for a 10 m × 10 m room ( RT≊300 ms) and mapped to the appropriate locations in the loudspeaker array. Results reveal a marked increase in perceptual weight applied to the initial click in reverberation, along with a reduction in the impact of late-arriving sound. In a second experiment, target stimuli were preceded by trains of "conditioner" sounds with or without reverberation. Effects were modest and limited to the first few clicks in a train, suggesting that impacts of reverberant pre-exposure on localization may be limited to the processing of information from early reflections.
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Dipeptidyl Peptidase-4 Inhibition Potentiates Stimulated Growth Hormone Secretion and Vasodilation in Women.
Journal of the American Heart Association (2018)
Wilson JR, Brown NJ, Nian H, Yu C, Bidlingmaier M, Devin JK.
Dipeptidyl Peptidase-4 Inhibition Potentiates Stimulated Growth Hormone Secretion and Vasodilation in Women.
J Am Heart Assoc.
2018 Feb 25;
7(5):.
Abstract: Diminished growth hormone (GH) is associated with impaired endothelial function and fibrinolysis. GH-releasing hormone is the primary stimulus for GH secretion and a substrate of dipeptidyl peptidase-4. We tested the hypothesis that dipeptidyl peptidase-4 inhibition with sitagliptin increases stimulated GH secretion, vasodilation, and tissue plasminogen activator (tPA) activity.
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Subclinical Compromise in Cardiac Strain Relates to Lower Cognitive Performances in Older Adults.
Journal of the American Heart Association (2018)
Kresge HA, Khan OA, Wagener MA, Liu D, Terry JG, Nair S, Cambronero FE, Gifford KA, Osborn KE, Hohman TJ, Pechman KR, Bell SP, Wang TJ, Carr JJ, Jefferson AL.
Subclinical Compromise in Cardiac Strain Relates to Lower Cognitive Performances in Older Adults.
J Am Heart Assoc.
2018 Feb 13;
7(4):.
Abstract: Global longitudinal strain (GLS), reflecting total shortening of the myocardium during the cardiac cycle, has emerged as a more precise myocardial function measure than left ventricular ejection fraction (LVEF). Longitudinal strain may be selectively affected in subclinical heart disease, even in the presence of normal LVEF. This study examines subclinical cardiac dysfunction, assessed by GLS and LVEF, and cognition among older adults.
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Prospective Associations Between Sleep Disturbance and Repetitive Negative Thinking: The Mediating Roles of Focusing and Shifting Attentional Control.
Behavior therapy (2018)
Cox RC, Cole DA, Kramer EL, Olatunji BO.
Prospective Associations Between Sleep Disturbance and Repetitive Negative Thinking: The Mediating Roles of Focusing and Shifting Attentional Control.
Behav Ther.
2018 Jan;
49(1):21-31.
Abstract: Although considerable evidence has linked sleep disturbance to symptoms of psychopathology, including repetitive negative thinking, few studies have examined how sleep disturbance may predict repetitive negative thinking over time. Further, no study to date has examined specific mechanisms that may account for this relationship. The present study sought to address these gaps in the literature by testing focusing and shifting attentional control as two potential mediators of the relationship between sleep disturbance and repetitive negative thinking over a 6-month period. A final sample of 445 unselected community participants completed measures of sleep disturbance and repetitive negative thinking at Time 1, measures of focusing and shifting attentional control 3 months later, and measures of repetitive negative thinking again 6 months later. Results revealed that focusing, but not shifting, attentional control mediated the relationship between sleep disturbance and repetitive negative thinking, specifically, worry, rumination, and obsessions. These findings provide preliminary evidence for focusing attentional control as a candidate mechanism that may explain the causal role of sleep disturbance in the development of repetitive negative thinking observed in various disorders.
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4D Multi-atlas Label Fusion using Longitudinal Images.
Patch-based techniques in medical imaging : third International Workshop, Patch-MI 2017, held in conjunction with MICCAI 2017, Quebec City, QC, Canada, September 14, 2017, Proceedings. Patch-MI (Workshop) (3rd : 2017 : Quebec, Quebec) (2017)
Huo Y, Resnick SM, Landman BA.
4D Multi-atlas Label Fusion using Longitudinal Images.
Patch Based Tech Med Imaging (2017).
2017;
10530:3-11.
Abstract: Longitudinal reproducibility is an essential concern in automated medical image segmentation, yet has proven to be an elusive objective as manual brain structure tracings have shown more than 10% variability. To improve reproducibility, longitudinal segmentation (4D) approaches have been investigated to reconcile temporal variations with traditional 3D approaches. In the past decade, multi-atlas label fusion has become a state-of-the-art segmentation technique for 3D image and many efforts have been made to adapt it to a 4D longitudinal fashion. However, the previous methods were either limited by using application specified energy function (e.g., surface fusion and multi model fusion) or only considered temporal smoothness on two consecutive time points (t and t+1) under sparsity assumption. Therefore, a 4D multi-atlas label fusion theory for general label fusion purpose and simultaneously considering temporal consistency on all time points is appealing. Herein, we propose a novel longitudinal label fusion algorithm, called 4D joint label fusion (4DJLF), to incorporate the temporal consistency modeling via non-local patch-intensity covariance models. The advantages of 4DJLF include: (1) 4DJLF is under the general label fusion framework by simultaneously incorporating the spatial and temporal covariance on all longitudinal time points. (2) The proposed algorithm is a longitudinal generalization of a leading joint label fusion method (JLF) that has proven adaptable to a wide variety of applications. (3) The spatial temporal consistency of atlases is modeled in a probabilistic model inspired from both voting based and statistical fusion. The proposed approach improves the consistency of the longitudinal segmentation while retaining sensitivity compared with original JLF approach using the same set of atlases. The method is available online in open-source.
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Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism.
BMC nephrology (2018)
Kaseda R, Tsuchida Y, Yang HC, Yancey PG, Zhong J, Tao H, Bian A, Fogo AB, Linton MRF, Fazio S, Ikizler TA, Kon V.
Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism.
BMC Nephrol.
2018 Jan 27;
19(1):17.
Abstract: Our aim was to evaluate lipid trafficking and inflammatory response of macrophages exposed to lipoproteins from subjects with moderate to severe chronic kidney disease (CKD), and to investigate the potential benefits of activating cellular cholesterol transporters via liver X receptor (LXR) agonism.
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Remote Microphone System Use at Home: Impact on Caregiver Talk.
Journal of speech, language, and hearing research : JSLHR (2018)
Benítez-Barrera CR, Angley GP, Tharpe AM.
Remote Microphone System Use at Home: Impact on Caregiver Talk.
J Speech Lang Hear Res.
2018 Feb 15;
61(2):399-409.
Abstract: The purpose of this study was to investigate the effects of home use of a remote microphone system (RMS) on the spoken language production of caregivers with young children who have hearing loss.
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Neighborhood Deprivation Predicts Heart Failure Risk in a Low-Income Population of Blacks and Whites in the Southeastern United States.
Circulation. Cardiovascular quality and outcomes (2018)
Akwo EA, Kabagambe EK, Harrell FE Jr, Blot WJ, Bachmann JM, Wang TJ, Gupta DK, Lipworth L.
Neighborhood Deprivation Predicts Heart Failure Risk in a Low-Income Population of Blacks and Whites in the Southeastern United States.
Circ Cardiovasc Qual Outcomes.
2018 Jan;
11(1):e004052.
Abstract: Recent data suggest that neighborhood socioeconomic environment predicts heart failure (HF) hospital readmissions. We investigated whether neighborhood deprivation predicts risk of incident HF beyond individual socioeconomic status in a low-income population.
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Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects.
Hypertension (Dallas, Tex. : 1979) (2018)
Elijovich F, Milne GL, Brown NJ, Laniado-Schwartzman M, Laffer CL.
Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects.
Hypertension.
2018 Feb;
71(2):346-355.
Abstract: We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na/24 hours, HiNa) and depletion (10 mEq Na/24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na, and Na/K ratio for the 3 days of the experiment combined (<0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na/K ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone (<0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na/K ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications.
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Randomized clinical trial of a single versus a double dose of 13-valent pneumococcal conjugate vaccine in adults 55 through 74 years of age previously vaccinated with 23-valent pneumococcal polysaccharide vaccine.
Vaccine (2018)
Jackson LA, El Sahly HM, George S, Winokur P, Edwards K, Brady RC, Rouphael N, Keitel WA, Mulligan MJ, Burton RL, Nakamura A, Ferreria J, Nahm MH.
Randomized clinical trial of a single versus a double dose of 13-valent pneumococcal conjugate vaccine in adults 55 through 74 years of age previously vaccinated with 23-valent pneumococcal polysaccharide vaccine.
Vaccine.
2018 Jan 29;
36(5):606-614.
Abstract: In older adults, prior administration of 23-valent pneumococcal polysaccharide vaccine (PPSV23) blunts the opsonophagocytic antibody (OPA) response to subsequent administration of 13-valent pneumococcal conjugate vaccine (PCV13). To determine whether a higher dose of PCV13 could mitigate this effect in adults 55 through 74 years of age, we compared OPA responses to a double dose of PCV13 in persons previously vaccinated with PPSV23 with responses to a single dose of PCV13 in previously vaccinated persons, and with a single dose in PPSV23 naïve persons.
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Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin.
Journal of the Endocrine Society (2017)
Wilson JR, Shuey MM, Brown NJ, Devin JK.
Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin.
J Endocr Soc.
2017 Sep 1;
1(9):1168-1178.
Abstract: Patients with diabetes often have comorbidities such as hypertension. It is not known how individual characteristics influence response to dipeptidyl peptidase-4 (DPP4) inhibitors.
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FTO affects food cravings and interacts with age to influence age-related decline in food cravings.
Physiology & behavior (2018)
Dang LC, Samanez-Larkin GR, Smith CT, Castrellon JJ, Perkins SF, Cowan RL, Claassen DO, Zald DH.
FTO affects food cravings and interacts with age to influence age-related decline in food cravings.
Physiol Behav.
2018 Aug 1;
192:188-193.
Abstract: The fat mass and obesity associated gene (FTO) was the first gene identified by genome-wide association studies to correlate with higher body mass index (BMI) and increased odds of obesity. FTO remains the locus with the largest and most replicated effect on body weight, but the mechanism whereby FTO affects body weight and the development of obesity is not fully understood. Here we tested whether FTO is associated with differences in food cravings and a key aspect of dopamine function that has been hypothesized to influence food reward mechanisms. Moreover, as food cravings and dopamine function are known to decline with age, we explored effects of age on relations between FTO and food cravings and dopamine function. Seven-eight healthy subjects between 22 and 83years old completed the Food Cravings Questionnaire and underwent genotyping for FTO rs9939609, the first FTO single nucleotide polymorphism associated with obesity. Compared to TT homozygotes, individuals carrying the obesity-susceptible A allele had higher total food cravings, which correlated with higher BMI. Additionally, food cravings declined with age, but this age effect differed across variants of FTO rs9939609: while TT homozygotes showed the typical age-related decline in food cravings, there was no such decline among A carriers. All subjects were scanned with [18F]fallypride PET to assess a recent proposal that at the neurochemical level FTO alters dopamine D2-like receptor (DRD2) function to influence food reward related mechanisms. However, we observed no evidence of FTO effects on DRD2 availability.
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"They have said that I was slightly depressed but there are circumstances that bring that on": How Middle-Aged and Older African American Men Describe Perceived Stress and Depression.
Ethnicity & disease (2017)
Cornish EK, Bergner EM, Griffith DM.
"They have said that I was slightly depressed but there are circumstances that bring that on": How Middle-Aged and Older African American Men Describe Perceived Stress and Depression.
Ethn Dis.
2017 Fall;
27(4):437-442.
Abstract: Few studies have focused on how men perceive stress and depression, and even fewer have examined how men of a specific racial or ethnic group describe their experiences of these conditions. African American men tend to define health in ways that are inclusive of their physical health, health behaviors, and mental health, but research has largely failed to explore how men put their health and mental health in social contexts. The objective of this article is to explore how middle-aged and older African American men who self-identify as having depression: 1) differentiate stress from depression; and 2) describe depression.
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Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
JCI insight (2017)
Deger SM, Hung AM, Gamboa JL, Siew ED, Ellis CD, Booker C, Sha F, Li H, Bian A, Stewart TG, Zent R, Mitch WE, Abumrad NN, Ikizler TA.
Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
JCI Insight.
2017 Nov 16;
2(22):.
Abstract: Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients.
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Anterior-posterior gradient differences in lobar and cingulate cortex cerebral blood flow in late-life depression.
Journal of psychiatric research (2018)
Abi Zeid Daou M, Boyd BD, Donahue MJ, Albert K, Taylor WD.
Anterior-posterior gradient differences in lobar and cingulate cortex cerebral blood flow in late-life depression.
J Psychiatr Res.
2018 Feb;
97:1-7.
Abstract: Vascular pathology is common in late-life depression, contributing to changes in cerebral function. We examined whether late-life depression was associated with differences in cerebral blood flow (CBF) and whether such differences were related to vascular risk and cerebrovascular pathology, specifically white matter hyperintensity (WMH) volumes. Twenty-three depressed elders and 20 age- and sex-matched elders with no psychiatric history completed cranial 3T MRI. MRI procedures included a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition obtained while on room air and during a hypercapnia challenge allowing for calculation of cerebrovascular reactivity (CVR). Brain segmentation identified frontal, temporal, parietal and cingulate sub-regions in which CBF and CVR were calculated. The depressed group exhibited an anterior-posterior gradient in CBF, with lower CBF throughout the frontal lobe but higher CBF in the parietal lobe, temporal lobe, thalamus and hippocampus. A similar anterior to posterior gradient was observed in the cingulate cortex, with anterior regions exhibiting lower CBF and posterior regions exhibiting higher CBF. We did not observe any group differences in CVR measures. We did not observe significant relationships between CBF and CVR with vascular risk or WMH volumes, aside from an isolated finding associating higher WMH volumes with lower CBF in the rostral anterior cingulate cortex. Decreased anterior CBF in depressed elders might reflect decreased metabolic activity in these regions, while increased posterior CBF may represent either compensatory processes or different activity of posterior intrinsic functional networks. Future work should examine how these findings are related to compensatory changes with aging.
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Postsecondary Expectations of High-School Students With Autism Spectrum Disorders.
Focus on autism and other developmental disabilities (2016)
Anderson KA, McDonald TA, Edsall D, Smith LE, Taylor JL.
Postsecondary Expectations of High-School Students With Autism Spectrum Disorders.
Focus Autism Other Dev Disabl.
2016;
31(1):16-26.
Abstract: This study examined the perceptions of adulthood among 31 high school students with autism spectrum disorder (ASD). We had two research aims: (1) to report students' postsecondary expectations in terms of school, work, friendships and living arrangement and (2) to describe how our sample defined adulthood. To better compare our sample's criteria of adulthood to the criteria traditionally endorsed in secondary schools, we used a directed content analysis approach. Data were derived from a semi-structured interview that questioned students about friendships, activities and the transition to adulthood. The majority of students expected to attain traditional markers of adulthood after high school; however, for some the pathways to achieving these outcomes were narrowly defined and perceived as a rigid, linear process. Independence, maturity and personal responsibility were the most highly endorsed characteristics of adulthood, followed by chronological age and traditional markers. Implications for transition planning and adult services are discussed.
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Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.
Journal of the American Heart Association (2017)
Marinos A, Gamboa A, Celedonio JE, Preheim BA, Okamoto LE, Ramirez CE, Arnold AC, Diedrich A, Biaggioni I, Shibao CA.
Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone.
J Am Heart Assoc.
2017 Nov 18;
6(11):.
Abstract: Black women have one of the highest prevalence rates of hypertension and obesity in the United States. We previously reported that sympathetic activation induced by obesity is a significant contributor to hypertension in white patients. It is unknown whether sympathetic activity similarly contributes to hypertension in obese black women.
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Lower cardiac index levels relate to lower cerebral blood flow in older adults.
Neurology (2017)
Jefferson AL, Liu D, Gupta DK, Pechman KR, Watchmaker JM, Gordon EA, Rane S, Bell SP, Mendes LA, Davis LT, Gifford KA, Hohman TJ, Wang TJ, Donahue MJ.
Lower cardiac index levels relate to lower cerebral blood flow in older adults.
Neurology.
2017 Dec 5;
89(23):2327-2334.
Abstract: To assess cross-sectionally whether lower cardiac index relates to lower resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) among older adults.
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Using Complementary and Alternative Medicine to Treat Pain and Agitation in Dementia: A Review of Randomized Controlled Trials from Long-Term Care with Potential Use in Critical Care.
Critical care nursing clinics of North America (2017)
Anderson AR, Deng J, Anthony RS, Atalla SA, Monroe TB.
Using Complementary and Alternative Medicine to Treat Pain and Agitation in Dementia: A Review of Randomized Controlled Trials from Long-Term Care with Potential Use in Critical Care.
Crit Care Nurs Clin North Am.
2017 Dec;
29(4):519-537.
Abstract: The risk of pain in adults with dementia worsens with advancing age. Painful comorbidities may be underassessed and inadequately treated. Receiving treatment in critical care settings may indicate greater occurrences of pain and complications. Pain may exacerbate behavioral and psychological symptoms of dementia (BPSD), such as agitation. Complementary and alternative medicine (CAM) therapies may alleviate pain and BPSD, and continuity of therapy may bolster these therapeutic effects. This review did not reveal an apparent benefit of aromatherapy; however, improvements in BPSD have been shown previously. Massage and human interaction did demonstrate efficacy in reducing BPSD and pain.
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Partial-volume correction increases estimated dopamine D2-like receptor binding potential and reduces adult age differences.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2019)
Smith CT, Crawford JL, Dang LC, Seaman KL, San Juan MD, Vijay A, Katz DT, Matuskey D, Cowan RL, Morris ED, Zald DH, Samanez-Larkin GR.
Partial-volume correction increases estimated dopamine D2-like receptor binding potential and reduces adult age differences.
J Cereb Blood Flow Metab.
2019 May;
39(5):822-833.
Abstract: The relatively modest spatial resolution of positron emission tomography (PET) increases the likelihood of partial volume effects such that binding potential (BP) may be underestimated. Given structural grey matter losses across adulthood, partial volume effects may be even more problematic in older age leading to overestimation of adult age differences. Here we examined the effects of partial volume correction (PVC) in two studies from different sites using different high-affinity D2-like radioligands (18 F-Fallypride, 11C-FLB457) and different PET camera resolutions (∼5 mm, 2.5 mm). Results across both data sets revealed that PVC increased estimated BP and reduced, though did not eliminate, age effects on BP. As expected, the effects of PVC were smaller in higher compared to lower resolution data. Analyses using uncorrected data that controlled for grey matter volume in each region of interest approximated PVC corrected data for some but not all regions. Overall, the findings suggest that PVC increases estimated BP in general and reduces adult age differences especially when using lower resolution cameras. The findings suggest that the past 30 years of research on dopamine receptor availability, for which very few studies use PVC, may overestimate effects of aging on dopamine receptor availability.
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Temporal binding of auditory spatial information across dynamic binaural events.
Attention, perception & psychophysics (2018)
Stecker GC.
Temporal binding of auditory spatial information across dynamic binaural events.
Atten Percept Psychophys.
2018 Jan;
80(1):14-20.
Abstract: Simultaneity judgments were used to measure temporal binding windows (TBW) for brief binaural events (changes in interaural time and/or level differences [ITD and ILD]) and test the hypothesis that ITD and ILD contribute to perception via separate sensory dimensions subject to binding via slow (100+ ms)-presumably cortical-mechanisms as in multisensory TBW. Stimuli were continuous low-frequency noises that included two brief shifts of either type (ITD or ILD), both of which are heard as lateral position changes. TBW for judgments within a single cue dimension were narrower for ITD (mean = 444 ms) than ILD (807 ms). TBW for judgments across cue dimensions (i.e., one ITD shift and one ILD shift) were similar to within-cue ILD (778 ms). The results contradict the original hypothesis, in that cross-cue comparisons were no slower than within-cue ILD comparisons. Rather, the wide TBW values-consistent with previous estimates of multisensory TBW-suggest slow integrative processing for both types of judgments. Narrower TBW for ITD than ILD judgments suggests important cue-specific differences in the neural mechanisms or the perceptual correlates of integration across binaural-cue dimensions.
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Somatic symptom presentations in women with fibromyalgia are differentially associated with elevated depression and anxiety.
Journal of health psychology (2020)
Hadlandsmyth K, Dailey DL, Rakel BA, Zimmerman MB, Vance CG, Merriwether EN, Chimenti RL, Geasland KM, Crofford LJ, Sluka KA.
Somatic symptom presentations in women with fibromyalgia are differentially associated with elevated depression and anxiety.
J Health Psychol.
2020 May;
25(6):819-829.
Abstract: This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression ( < 0.05). Pain severity, pain catastrophizing, and fear of movement were associated with high anxiety and high depression ( < 0.05). Possible implications for underlying mechanisms and the need for targeted treatments are discussed.
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Tongue- and Jaw-Specific Contributions to Acoustic Vowel Contrast Changes in the Diphthong /ai/ in Response to Slow, Loud, and Clear Speech.
Journal of speech, language, and hearing research : JSLHR (2017)
Mefferd AS.
Tongue- and Jaw-Specific Contributions to Acoustic Vowel Contrast Changes in the Diphthong /ai/ in Response to Slow, Loud, and Clear Speech.
J Speech Lang Hear Res.
2017 Nov 9;
60(11):3144-3158.
Abstract: This study sought to determine decoupled tongue and jaw displacement changes and their specific contributions to acoustic vowel contrast changes during slow, loud, and clear speech.
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Comparing the effects of age, pubertal development, and symptom profile on cortisol rhythm in children and adolescents with autism spectrum disorder.
Autism research : official journal of the International Society for Autism Research (2018)
Muscatello RA, Corbett BA.
Comparing the effects of age, pubertal development, and symptom profile on cortisol rhythm in children and adolescents with autism spectrum disorder.
Autism Res.
2018 Jan;
11(1):110-120.
Abstract: Previous studies in children with autism spectrum disorder (ASD) have shown elevated evening cortisol; however, few studies have examined diurnal rhythm in adolescents with ASD. Adolescence is a time of significant physical and psychological change, and dysregulation of the hypothalamic-pituitary-adrenal axis may put adolescents with ASD at increased risk for internalizing disorders, such as anxiety and depression. The extent to which cortisol levels are associated with age, puberty and symptom profile was examined in 113 youth (ages 7-17) with ASD and typical development. Salivary samples were collected over 3 days in the home, 4 times per day (waking, 30-min post-waking, afternoon, evening). Results showed youth with ASD had higher evening cortisol and a blunted diurnal slope relative to TD youth. Pubertal development and age were significant predictors of evening cortisol, and adolescents with ASD had higher evening cortisol levels compared to children with ASD. The study extends previous reports of elevated evening cortisol in children with ASD to reveal high levels in adolescence as well. Adolescents with ASD also show a significantly blunted diurnal slope, which may be associated with risk of internalizing symptoms. Findings suggest elevated evening cortisol persists across development in youth with ASD, thus emphasizing a need to identify potential negative effects of excess cortisol exposure on health in ASD individuals. Autism Res 2018, 11: 110-120. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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Disrupted integration of exteroceptive and interoceptive signaling in autism spectrum disorder.
Autism research : official journal of the International Society for Autism Research (2018)
Noel JP, Lytle M, Cascio C, Wallace MT.
Disrupted integration of exteroceptive and interoceptive signaling in autism spectrum disorder.
Autism Res.
2018 Jan;
11(1):194-205.
Abstract: In addition to deficits in social communication, individuals diagnosed with Autism Spectrum Disorder (ASD) frequently exhibit changes in sensory and multisensory function. Recent evidence has focused on changes in audiovisual temporal processing, and has sought to relate these sensory-based changes to weaknesses in social communication. These changes in audiovisual temporal function manifest as differences in the temporal epoch or "window" within which paired auditory and visual stimuli are integrated or bound, with those with ASD exhibiting expanded audiovisual temporal binding windows (TBWs). However, it is unknown whether this impairment is unique to audiovisual pairings, perhaps because of their relevance for speech processing, or whether it generalizes across pairings in different sensory modalities. In addition to the exteroceptive senses, there has been growing interest in ASD research in interoception (e.g., the monitoring of respiration, heartbeat, hunger, etc.), as these internally directed sensory processes appear to be altered as well in autism. In the current study, we sought to examine both exteroception and interoception in individuals with ASD and a group of typically developing (TD) matched controls, with an emphasis on temporal perception of audiovisual (exteroceptive) and cardiovisual (interoceptive to exteroceptive) cues. Results replicate prior findings showing expanded audiovisual TBWs in ASD in comparison to TD. In addition, strikingly, cardiovisual TBWs were fourfold larger in ASD than in TD, suggesting a putative complete lack of cardiovisual temporal acuity in ASD individuals. Results are discussed in light of recent evidence indicating a reduced tendency to rely on sensory priors in ASD. Autism Res 2018, 11: 194-205. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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"Health is the Ability to Manage Yourself Without Help": How Older African American Men Define Health and Successful Aging.
The journals of gerontology. Series B, Psychological sciences and social sciences (2018)
Griffith DM, Cornish EK, Bergner EM, Bruce MA, Beech BM.
"Health is the Ability to Manage Yourself Without Help": How Older African American Men Define Health and Successful Aging.
J Gerontol B Psychol Sci Soc Sci.
2018 Jan 11;
73(2):240-247.
Abstract: Few studies have explored how older African American men understand the relationship between health and successful aging. The goal of this study was to examine how older African American men's conceptions and definitions of health and notions of successful aging are interrelated.
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Sex Differences in the Psychophysical Response to Contact Heat in Moderate Cognitive Impairment Alzheimer's Disease: A Cross-Sectional Brief Report.
Journal of Alzheimer's disease : JAD (2017)
Cowan RL, Beach PA, Atalla SW, Dietrich MS, Bruehl SP, Deng J, Wang J, Newhouse PA, Gore JC, Monroe TB.
Sex Differences in the Psychophysical Response to Contact Heat in Moderate Cognitive Impairment Alzheimer's Disease: A Cross-Sectional Brief Report.
J Alzheimers Dis.
2017;
60(4):1633-1640.
Abstract: People with Alzheimer's disease (AD) report pain less frequently and receive less pain medication than people without AD. Recent studies have begun to elucidate how pain may be altered in those with AD. However, potential sex differences in pain responsiveness have never been explored in these patients. It is unclear whether sex differences found in prior studies of healthy young and older individuals extend to people with AD.
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Spontaneous Eye Blink Rate (EBR) Is Uncorrelated with Dopamine D2 Receptor Availability and Unmodulated by Dopamine Agonism in Healthy Adults.
eNeuro (2017)
Dang LC, Samanez-Larkin GR, Castrellon JJ, Perkins SF, Cowan RL, Newhouse PA, Zald DH.
Spontaneous Eye Blink Rate (EBR) Is Uncorrelated with Dopamine D2 Receptor Availability and Unmodulated by Dopamine Agonism in Healthy Adults.
eNeuro.
2017 Sep-Oct;
4(5):.
Abstract: Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults. Here we measured EBR in healthy human subjects whose dopamine D2 receptor (DRD2) availability was assessed with positron emission tomography (PET)-[18F]fallypride to examine the predictive power of EBR for DRD2 availability. Effects of the dopamine agonist bromocriptine on EBR also were examined to determine the responsiveness of EBR to dopaminergic stimulation and, in light of the hypothesized inverted-U profile of dopamine effects, the role of DRD2 availability in EBR responsivity to bromocriptine. Results from 20 subjects (age 33.6 ± 7.6 years, 9F) showed no relation between EBR and DRD2 availability. EBR also was not responsive to dopaminergic stimulation by bromocriptine, and individual differences in DRD2 availability did not modulate EBR responsivity to bromocriptine. Given that EBR is hypothesized to be particularly sensitive to DRD2 function, these findings suggest caution in using EBR as a proxy for dopamine function in healthy humans.
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Secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis.
Clinical rheumatology (2018)
Hanaoka BY, Ormseth MJ, Michael Stein C, Banerjee D, Nikolova-Karakashian M, Crofford LJ.
Secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis.
Clin Rheumatol.
2018 May;
37(5):1395-1399.
Abstract: The goals of this study were to determine if secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis (RA) compared to control subjects and to examine the relationships of S-SMase activity with functional status, quality of life, and RA disease activity measurements. We collected data on 33 patients who were diagnosed with RA and 17 non-RA controls who were comparable in terms of age, sex, and race. Demographic, clinical data and self-reported measures of fatigue, pain, and physical function were obtained directly from patients and controls. RA patients also completed quantitative joint assessment using a 28-joint count and functional status and quality of life assessment using the Modified Health Assessment Questionnaire (MHAQ). Archived serum samples were used to analyze retrospectively serum S-SMase activity in patients and controls. The mean serum S-SMase activity was 1.4-fold higher in patients with RA (RA 2.8 ± 1.0 nmol/ml/h vs. controls 2.0 ± 0.8 nmol/ml/h; p = 0.014). Spearman's rho correlations between S-SMase activity and oxidant activity, markers of inflammation and endothelial activation with the exception of P-selectin (rho = 0.40, p = 0.034), measures of disease activity, functional status, and quality of life were not statistically significant in patients with RA. We confirmed that S-SMase activity is higher among RA patients compared to controls, as in other acute and chronic inflammatory diseases. Future studies can build on the present findings to understand more fully the biologic role(s) of S-SMase activity in RA.
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Brief Report: Postsecondary Work and Educational Disruptions for Youth on the Autism Spectrum.
Journal of autism and developmental disorders (2017)
Taylor JL, DaWalt LS.
Brief Report: Postsecondary Work and Educational Disruptions for Youth on the Autism Spectrum.
J Autism Dev Disord.
2017 Dec;
47(12):4025-4031.
Abstract: This study examined vocational/educational disruption in the 2-3 years after high school for 36 youth with autism spectrum disorder (ASD). Data were collected three times from parents: during youth's last year of high school and two times after high school exit. Data were coded into categories indicating any versus no disruptions in postsecondary vocation/education, and group differences in individual (behavior problems, IQ, adaptive behavior, autism severity, stress reactivity) and family (parent depression, anxiety, quality of life; family income and climate) factors were examined. One-half of youth had experienced a postsecondary vocational/educational disruption; parents of those with a disruption had more depressive and anxiety symptoms and lower quality of life while their son/daughter was still in high school.
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Cloud Engineering Principles and Technology Enablers for Medical Image Processing-as-a-Service.
Proceedings of the IEEE International Conference on Cloud Engineering. IEEE International Conference on Cloud Engineering (2017)
Bao S, Plassard AJ, Landman BA, Gokhale A.
Cloud Engineering Principles and Technology Enablers for Medical Image Processing-as-a-Service.
Proc IEEE Int Conf Cloud Eng.
2017 Apr;
2017:127-137.
Abstract: Traditional in-house, laboratory-based medical imaging studies use hierarchical data structures (e.g., NFS file stores) or databases (e.g., COINS, XNAT) for storage and retrieval. The resulting performance from these approaches is, however, impeded by standard network switches since they can saturate network bandwidth during transfer from storage to processing nodes for even moderate-sized studies. To that end, a cloud-based "medical image processing-as-a-service" offers promise in utilizing the ecosystem of Apache Hadoop, which is a flexible framework providing distributed, scalable, fault tolerant storage and parallel computational modules, and HBase, which is a NoSQL database built atop Hadoop's distributed file system. Despite this promise, HBase's load distribution strategy of region split and merge is detrimental to the hierarchical organization of imaging data (e.g., project, subject, session, scan, slice). This paper makes two contributions to address these concerns by describing key cloud engineering principles and technology enhancements we made to the Apache Hadoop ecosystem for medical imaging applications. First, we propose a row-key design for HBase, which is a necessary step that is driven by the hierarchical organization of imaging data. Second, we propose a novel data allocation policy within HBase to strongly enforce collocation of hierarchically related imaging data. The proposed enhancements accelerate data processing by minimizing network usage and localizing processing to machines where the data already exist. Moreover, our approach is amenable to the traditional scan, subject, and project-level analysis procedures, and is compatible with standard command line/scriptable image processing software. Experimental results for an illustrative sample of imaging data reveals that our new HBase policy results in a three-fold time improvement in conversion of classic DICOM to NiFTI file formats when compared with the default HBase region split policy, and nearly a six-fold improvement over a commonly available network file system (NFS) approach even for relatively small file sets. Moreover, file access latency is lower than network attached storage.
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Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials.
Diabetes care (2017)
Nathan BM, Boulware D, Geyer S, Atkinson MA, Colman P, Goland R, Russell W, Wentworth JM, Wilson DM, Evans-Molina C, Wherrett D, Skyler JS, Moran A, Sosenko JM, Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups..
Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials.
Diabetes Care.
2017 Nov;
40(11):1494-1499.
Abstract: We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants.
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Mechanisms of Cognitive Aging in the HIV-Positive Adult.
Current behavioral neuroscience reports (2017)
Kamkwalala A, Newhouse P.
Mechanisms of Cognitive Aging in the HIV-Positive Adult.
Curr Behav Neurosci Rep.
2017 Sep;
4(3):188-197.
Abstract: As of the year 2016, an estimated 50% of the United States' HIV-Positive population is aged 50 years or older. Due to a combination of increased rates of infection in older adults, and successful anti-retroviral (ART) regimens allowing HIV-positive adults to survive for decades with the disease, we are now faced with a steadily graying HIV-positive population, with only limited knowledge of how the cognitive and physiological effects of aging intersect with those of chronic HIV-infection.
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Recruitment methods for survey research: Findings from the Mid-South Clinical Data Research Network.
Contemporary clinical trials (2017)
Heerman WJ, Jackson N, Roumie CL, Harris PA, Rosenbloom ST, Pulley J, Wilkins CH, Williams NA, Crenshaw D, Leak C, Scherdin J, Muñoz D, Bachmann J, Rothman RL, Kripalani S.
Recruitment methods for survey research: Findings from the Mid-South Clinical Data Research Network.
Contemp Clin Trials.
2017 Nov;
62:50-55.
Abstract: The objective of this study was to report survey response rates and demographic characteristics of eight recruitment approaches to determine acceptability and effectiveness of large-scale patient recruitment among various populations.
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Multi-Scale Hippocampal Parcellation Improves Atlas-Based Segmentation Accuracy.
Proceedings of SPIE--the International Society for Optical Engineering (2017)
Plassard AJ, McHugo M, Heckers S, Landman BA.
Multi-Scale Hippocampal Parcellation Improves Atlas-Based Segmentation Accuracy.
Proc SPIE Int Soc Opt Eng.
2017 Feb 11;
10133:.
Abstract: Known for its distinct role in memory, the hippocampus is one of the most studied regions of the brain. Recent advances in magnetic resonance imaging have allowed for high-contrast, reproducible imaging of the hippocampus. Typically, a trained rater takes 45 minutes to manually trace the hippocampus and delineate the anterior from the posterior segment at millimeter resolution. As a result, there has been a significant desire for automated and robust segmentation of the hippocampus. In this work we use a population of 195 atlases based on T1-weighted MR images with the left and right hippocampus delineated into the head and body. We initialize the multi-atlas segmentation to a region directly around each lateralized hippocampus to both speed up and improve the accuracy of registration. This initialization allows for incorporation of nearly 200 atlases, an accomplishment which would typically involve hundreds of hours of computation per target image. The proposed segmentation results in a Dice similiarity coefficient over 0.9 for the full hippocampus. This result outperforms a multi-atlas segmentation using the BrainCOLOR atlases (Dice 0.85) and FreeSurfer (Dice 0.75). Furthermore, the head and body delineation resulted in a Dice coefficient over 0.87 for both structures. The head and body volume measurements also show high reproducibility on the Kirby 21 reproducibility population (R greater than 0.95, p < 0.05 for all structures). This work signifies the first result in an ongoing work to develop a robust tool for measurement of the hippocampus and other temporal lobe structures.
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Theoretical and Empirical Comparison of Big Data Image Processing with Apache Hadoop and Sun Grid Engine.
Proceedings of SPIE--the International Society for Optical Engineering (2017)
Bao S, Weitendorf FD, Plassard AJ, Huo Y, Gokhale A, Landman BA.
Theoretical and Empirical Comparison of Big Data Image Processing with Apache Hadoop and Sun Grid Engine.
Proc SPIE Int Soc Opt Eng.
2017 Feb 11;
10138:.
Abstract: The field of big data is generally concerned with the scale of processing at which traditional computational paradigms break down. In medical imaging, traditional large scale processing uses a cluster computer that combines a group of workstation nodes into a functional unit that is controlled by a job scheduler. Typically, a shared-storage network file system (NFS) is used to host imaging data. However, data transfer from storage to processing nodes can saturate network bandwidth when data is frequently uploaded/retrieved from the NFS, e.g., "short" processing times and/or "large" datasets. Recently, an alternative approach using Hadoop and HBase was presented for medical imaging to enable co-location of data storage and computation while minimizing data transfer. The benefits of using such a framework must be formally evaluated against a traditional approach to characterize the point at which simply "large scale" processing transitions into "big data" and necessitates alternative computational frameworks. The proposed Hadoop system was implemented on a production lab-cluster alongside a standard Sun Grid Engine (SGE). Theoretical models for wall-clock time and resource time for both approaches are introduced and validated. To provide real example data, three T1 image archives were retrieved from a university secure, shared web database and used to empirically assess computational performance under three configurations of cluster hardware (using 72, 109, or 209 CPU cores) with differing job lengths. Empirical results match the theoretical models. Based on these data, a comparative analysis is presented for when the Hadoop framework will be relevant and non-relevant for medical imaging.
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Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses.
Clinical and vaccine immunology : CVI (2017)
Falloon J, Talbot HK, Curtis C, Ervin J, Krieger D, Dubovsky F, Takas T, Yu J, Yu L, Lambert SL, Villafana T, Esser MT.
Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses.
Clin Vaccine Immunol.
2017 Sep;
24(9):.
Abstract: This is the second phase 1 study of a respiratory syncytial virus (RSV) vaccine containing RSV fusion protein (sF) adjuvanted with glucopyranosyl lipid A (GLA) in a squalene-based 2% stable emulsion (GLA-SE). In this randomized, double-blind study, 261 subjects aged ≥60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 μg sF with escalating doses of GLA (1, 2.5, or 5 μg) in SE, or a vaccine containing 80 μg sF with 2.5 μg GLA in SE. Subjects receiving 120 μg sF with 2.5 or 5 μg GLA were also randomized to receive IIV or placebo. Immunity to RSV was assessed by detection of microneutralizing, anti-F immunoglobulin G, and palivizumab-competitive antibodies and F-specific gamma interferon enzyme-linked immunosorbent spot assay T-cell responses. Higher adjuvant doses increased injection site discomfort, but at the highest dose, the reactogenicity was similar to that of IIV. Significant humoral and cellular immune responses were observed. The 120 μg sF plus 5.0 μg GLA formulation resulted in the highest responses in all subjects and in older subjects. These results confirm previous observations of vaccine tolerability, safety, and immunogenicity and were used to select the 120 μg sF plus 5.0 μg GLA formulation for phase 2 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT02289820.).
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Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells.
Journal of immunology (Baltimore, Md. : 1950) (2017)
Spurlock CF 3rd, Shaginurova G, Tossberg JT, Hester JD, Chapman N, Guo Y, Crooke PS 3rd, Aune TM.
Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells.
J Immunol.
2017 Jul 15;
199(2):547-558.
Abstract: We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4 T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs. Novel enhancer-associated lncRNAs transcribed from the locus bind the transcription factor NF-κB and enhance binding of NF-κB to the genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one enhancer-associated lncRNA abrogates expression by memory T cells, indicating these lncRNAs have biologic function.
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Spatiotemporal movement variability in ALS: Speaking rate effects on tongue, lower lip, and jaw motor control.
Journal of communication disorders (2017)
Kuruvilla-Dugdale M, Mefferd A.
Spatiotemporal movement variability in ALS: Speaking rate effects on tongue, lower lip, and jaw motor control.
J Commun Disord.
2017 May;
67:22-34.
Abstract: Although it is frequently presumed that bulbar muscle degeneration in Amyotrophic Lateral Sclerosis (ALS) is associated with progressive loss of speech motor control, empirical evidence is limited. Furthermore, because speaking rate slows with disease progression and rate manipulations are used to improve intelligibility in ALS, this study sought to (i) determine between and within-group differences in articulatory motor control as a result of speaking rate changes and (ii) identify the strength of association between articulatory motor control and speech impairment severity.
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Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular Evoked Myogenic Potential.
American journal of audiology (2017)
Makowiec K, McCaslin DL, Jacobson GP, Hatton K, Lee J.
Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular Evoked Myogenic Potential.
Am J Audiol.
2017 Jun 13;
26(2):180-188.
Abstract: The purpose of this investigation was to identify the optimal recording parameters for evoking the ocular vestibular evoked myogenic potential (oVEMP) using air-conduction stimuli.
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Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross-Sectional Resting State Functional Connectivity Study.
Pain medicine (Malden, Mass.) (2018)
Monroe TB, Fillingim RB, Bruehl SP, Rogers BP, Dietrich MS, Gore JC, Atalla SW, Cowan RL.
Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross-Sectional Resting State Functional Connectivity Study.
Pain Med.
2018 Sep 1;
19(9):1737-1747.
Abstract: A long-standing hypothesis is that when compared with males, females may be at increased risk of experiencing greater pain sensitivity and unpleasantness. The purpose of this study was to examine sex differences in pain psychophysics and resting state functional connectivity (RSFC) in core pain regions in an age- and sex-matched sample of healthy older adults.
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Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry (2017)
Vega JN, Dumas J, Newhouse PA.
Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.
Am J Geriatr Psychiatry.
2017 Dec;
25(12):1415-1426.
Abstract: Advances in cancer treatment are producing a growing number of cancer survivors; therefore, issues surrounding quality of life during and following cancer treatment have become increasingly important. Chemotherapy-related cognitive impairment (CRCI) is a problem that is commonly reported following the administration of chemotherapy treatment in patients with cancer. Research suggests that CRCI can persist for months to years after completing treatment, which has implications for the trajectory of normal and pathologic cognitive aging for the growing number of long-term cancer survivors. These problems are particularly relevant for older individuals, given that cancer is largely a disease of older age, and the number of patients with cancer who are aged 65 years or older will increase dramatically over the coming decades. This review will briefly summarize empirical findings related to CRCI, discuss CRCI in older patients with cancer, propose potential causative hypotheses, and provide a canonical patient case to illustrate how CRCI presents clinically. Finally, potential intervention strategies for CRCI will be highlighted and issues to consider when evaluating older patients with a history of cancer will be discussed.
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Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry (2017)
Riddle M, Potter GG, McQuoid DR, Steffens DC, Beyer JL, Taylor WD.
Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression.
Am J Geriatr Psychiatry.
2017 Oct;
25(10):1123-1134.
Abstract: Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined.
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Estrogen enhances hippocampal gray-matter volume in young and older postmenopausal women: a prospective dose-response study.
Neurobiology of aging (2017)
Albert K, Hiscox J, Boyd B, Dumas J, Taylor W, Newhouse P.
Estrogen enhances hippocampal gray-matter volume in young and older postmenopausal women: a prospective dose-response study.
Neurobiol Aging.
2017 Aug;
56:1-6.
Abstract: Estrogen administration following menopause has been shown to support hippocampally mediated cognitive processes. A number of previous studies have examined the effect of estrogen on hippocampal structure to determine the mechanism underlying estrogen effects on hippocampal function. However, these studies have been largely observational and provided inconsistent results. We examined the effect of short-term estradiol administration on hippocampal gray-matter volume in a prospective study with multiple doses of estradiol (placebo, 1 mg, and 2 mg). Following 3 months of estradiol administration, bilateral posterior hippocampal voxel-based gray-matter volume was increased in women who received 2-mg estradiol. There were no significant differences in total hippocampal volume and no significant effects on gray-matter volume in women who received placebo or 1-mg estradiol. These findings accord with previous animal studies and provide evidence of estrogen effects on hippocampal morphology that may represent a neurobiological mechanism for estrogen effects on cognition in postmenopausal women.
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Pain interference and depressive symptoms in communicative people with Alzheimer's disease: a pilot study.
Aging & mental health (2018)
Wang J, Dietrich MS, Simmons SF, Cowan RL, Monroe TB.
Pain interference and depressive symptoms in communicative people with Alzheimer's disease: a pilot study.
Aging Ment Health.
2018 Jun;
22(6):808-812.
Abstract: To examine pain interference in verbally communicative older adults with mild to moderate Alzheimer's disease (AD) and to examine the association of pain interference with cognitive function and depressive symptoms.
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The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.
Translational psychiatry (2017)
Smith CT, Dang LC, Buckholtz JW, Tetreault AM, Cowan RL, Kessler RM, Zald DH.
The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.
Transl Psychiatry.
2017 Apr 11;
7(4):e1091.
Abstract: Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BP), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BP (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n=84), we tested for effects of the C957T and -141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BP of the high-affinity D2 receptor tracer F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BP bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BP in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.
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Clusters of Healthy and Unhealthy Eating Behaviors Are Associated With Body Mass Index Among Adults.
Journal of nutrition education and behavior (2017)
Heerman WJ, Jackson N, Hargreaves M, Mulvaney SA, Schlundt D, Wallston KA, Rothman RL.
Clusters of Healthy and Unhealthy Eating Behaviors Are Associated With Body Mass Index Among Adults.
J Nutr Educ Behav.
2017 May;
49(5):415-421.e1.
Abstract: To identify eating styles from 6 eating behaviors and test their association with body mass index (BMI) among adults.
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Multisensory speech perception in autism spectrum disorder: From phoneme to whole-word perception.
Autism research : official journal of the International Society for Autism Research (2017)
Stevenson RA, Baum SH, Segers M, Ferber S, Barense MD, Wallace MT.
Multisensory speech perception in autism spectrum disorder: From phoneme to whole-word perception.
Autism Res.
2017 Jul;
10(7):1280-1290.
Abstract: Speech perception in noisy environments is boosted when a listener can see the speaker's mouth and integrate the auditory and visual speech information. Autistic children have a diminished capacity to integrate sensory information across modalities, which contributes to core symptoms of autism, such as impairments in social communication. We investigated the abilities of autistic and typically-developing (TD) children to integrate auditory and visual speech stimuli in various signal-to-noise ratios (SNR). Measurements of both whole-word and phoneme recognition were recorded. At the level of whole-word recognition, autistic children exhibited reduced performance in both the auditory and audiovisual modalities. Importantly, autistic children showed reduced behavioral benefit from multisensory integration with whole-word recognition, specifically at low SNRs. At the level of phoneme recognition, autistic children exhibited reduced performance relative to their TD peers in auditory, visual, and audiovisual modalities. However, and in contrast to their performance at the level of whole-word recognition, both autistic and TD children showed benefits from multisensory integration for phoneme recognition. In accordance with the principle of inverse effectiveness, both groups exhibited greater benefit at low SNRs relative to high SNRs. Thus, while autistic children showed typical multisensory benefits during phoneme recognition, these benefits did not translate to typical multisensory benefit of whole-word recognition in noisy environments. We hypothesize that sensory impairments in autistic children raise the SNR threshold needed to extract meaningful information from a given sensory input, resulting in subsequent failure to exhibit behavioral benefits from additional sensory information at the level of whole-word recognition. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1280-1290. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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Frontocingulate cerebral blood flow and cerebrovascular reactivity associated with antidepressant response in late-life depression.
Journal of affective disorders (2017)
Abi Zeid Daou M, Boyd BD, Donahue MJ, Albert K, Taylor WD.
Frontocingulate cerebral blood flow and cerebrovascular reactivity associated with antidepressant response in late-life depression.
J Affect Disord.
2017 Jun;
215:103-110.
Abstract: Vascular pathology is common in late-life depression (LLD) and may contribute to alterations in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). In turn, such hemodynamic deficits may adversely affect brain function and clinical course. The goal of this study was to examine whether altered cerebral hemodynamics in depressed elders predicted antidepressant response.
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Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.
Journal of Alzheimer's disease : JAD (2017)
Mason EJ, Hussey EP, Molitor RJ, Ko PC, Donahue MJ, Ally BA.
Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.
J Alzheimers Dis.
2017;
57(3):735-745.
Abstract: Early detection may be the key to developing therapies that will combat Alzheimer's disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40-60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects' medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.
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Reducing the Diagnostic Heterogeneity of Schizoaffective Disorder.
Frontiers in psychiatry (2017)
Seldin K, Armstrong K, Schiff ML, Heckers S.
Reducing the Diagnostic Heterogeneity of Schizoaffective Disorder.
Front Psychiatry.
2017;
8:18.
Abstract: Clinical outcome studies of schizoaffective disorder patients have yielded conflicting results. One reason is the heterogeneity of samples drawn from the schizoaffective disorder population. Here, we studied schizoaffective disorder patients who showed marked functional impairment and continuous signs of illness for at least 6 months (i.e., DSM criteria B and C for schizophrenia).
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The Impact of Alzheimer's Disease on the Resting State Functional Connectivity of Brain Regions Modulating Pain: A Cross Sectional Study.
Journal of Alzheimer's disease : JAD (2017)
Monroe TB, Beach PA, Bruehl SP, Dietrich MS, Rogers BP, Gore JC, Atalla SW, Cowan RL.
The Impact of Alzheimer's Disease on the Resting State Functional Connectivity of Brain Regions Modulating Pain: A Cross Sectional Study.
J Alzheimers Dis.
2017;
57(1):71-83.
Abstract: It is currently unknown why people with Alzheimer's disease (AD) receive less pain medication and report pain less frequently.
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Reduced effects of age on dopamine D2 receptor levels in physically active adults.
NeuroImage (2017)
Dang LC, Castrellon JJ, Perkins SF, Le NT, Cowan RL, Zald DH, Samanez-Larkin GR.
Reduced effects of age on dopamine D2 receptor levels in physically active adults.
Neuroimage.
2017 Mar 1;
148:123-129.
Abstract: Physical activity has been shown to ameliorate dopaminergic degeneration in non-human animal models. However, the effects of regular physical activity on normal age-related changes in dopamine function in humans are unknown. Here we present cross-sectional data from forty-four healthy human subjects between 23 and 80 years old, showing that typical age-related dopamine D2 receptor loss, assessed with PET [18F]fallypride, was significantly reduced in physically active adults compared to less active adults.
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Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2018)
Watchmaker JM, Juttukonda MR, Davis LT, Scott AO, Faraco CC, Gindville MC, Jordan LC, Cogswell PM, Jefferson AL, Kirshner HS, Donahue MJ.
Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients.
J Cereb Blood Flow Metab.
2018 Sep;
38(9):1618-1630.
Abstract: Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38-0.45) compared to controls (interquartile range = 0.29-0.38), similar to participants with SCA (interquartile range = 0.37-0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.
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Attention bias in older women with remitted depression is associated with enhanced amygdala activity and functional connectivity.
Journal of affective disorders (2017)
Albert K, Gau V, Taylor WD, Newhouse PA.
Attention bias in older women with remitted depression is associated with enhanced amygdala activity and functional connectivity.
J Affect Disord.
2017 Mar 1;
210:49-56.
Abstract: Cognitive bias is a common characteristic of major depressive disorder (MDD) and is posited to remain during remission and contribute to recurrence risk. Attention bias may be related to enhanced amygdala activity or altered amygdala functional connectivity in depression. The current study examined attention bias, brain activity for emotional images, and functional connectivity in post-menopausal women with and without a history of major depression.
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Sex differences in sodium deposition in human muscle and skin.
Magnetic resonance imaging (2017)
Wang P, Deger MS, Kang H, Ikizler TA, Titze J, Gore JC.
Sex differences in sodium deposition in human muscle and skin.
Magn Reson Imaging.
2017 Feb;
36:93-97.
Abstract: The aim of this work was to investigate possible sex differences in the patterns of sodium deposition between muscle and skin using sodium MRI. A total of 38 subjects were examined for comparisons: 20 males, aged 25-79years with a median age of 51; 18 females, aged 38-66years, median age 53. All subjects underwent sodium MRI scans of the calf muscles together with cross sections through four calibration standards containing known sodium contents (10mM, 20mM, 30mM, and 40mM). Tissue sodium concentrations (TSC) in muscle and skin were then calculated by comparing signal intensities between tissues and reference standards using a linear analysis. A Wilcoxon rank sum test was applied to the ΔTSC (=TSC-TSC) series of males and females to examine if they were significantly different. Finally, a multiple linear regression was utilized to account for the effects from two potential confounders, age and body mass index (BMI). We found that sodium content appears to be higher in skin than in muscle for men, however women tend to have higher muscle sodium than skin sodium. This sex-relevant sodium deposition is statistically significant (P=3.10×10) by the Wilcoxon rank sum test, and this difference in distribution seems to be more reliable with increasing age. In the multiple linear regression, gender still has a statistically significant effect (P<1.0×10) on the difference between sodium deposition in muscle and skin, while taking the effects of age and BMI into account.
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Manual segmentation of the human bed nucleus of the stria terminalis using 3T MRI.
NeuroImage (2017)
Theiss JD, Ridgewell C, McHugo M, Heckers S, Blackford JU.
Manual segmentation of the human bed nucleus of the stria terminalis using 3T MRI.
Neuroimage.
2017 Feb 1;
146:288-292.
Abstract: The bed nucleus of the stria terminalis (BNST)-a small gray matter region located in the basal forebrain-has been implicated in both anxiety and addiction based on compelling evidence from rodent and non-human primate studies. However, the BNST's small size and proximity to other gray matter regions has hindered non-invasive study in human subjects using standard neuroimaging methods. While initial studies have benefitted from a BNST mask created from a single human subject using a 7T scanner, individual variability is likely-especially in patient populations-thus a manual segmentation protocol is needed. Here we report on the development of a reliable manual segmentation protocol performed on 3T MRI images using a scanning sequence that provides high gray matter/white matter/cerebrospinal fluid contrast. Inter- and intra-rater reliabilities, measured in 10 healthy individuals, demonstrate that the protocol can be reliably implemented (intra-rater Dice similarity coefficient≥0.85, inter-rater≥0.77). This BNST tracing protocol provides the necessary foundation for future 3T MRI studies of the BNST in healthy controls and patient populations.
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Nonclassic features of pseudohypoparathyroidism type 1A.
Current opinion in endocrinology, diabetes, and obesity (2017)
Shoemaker AH, Jüppner H.
Nonclassic features of pseudohypoparathyroidism type 1A.
Curr Opin Endocrinol Diabetes Obes.
2017 Feb;
24(1):33-38.
Abstract: To provide readers with a review of contemporary literature describing the evolving understanding of the pseudohypoparathyroidism type 1A (PHP1A) phenotype.
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Adult age differences in decision making across domains: Increased discounting of social and health-related rewards.
Psychology and aging (2016)
Seaman KL, Gorlick MA, Vekaria KM, Hsu M, Zald DH, Samanez-Larkin GR.
Adult age differences in decision making across domains: Increased discounting of social and health-related rewards.
Psychol Aging.
2016 Nov;
31(7):737-746.
Abstract: Although research on aging and decision making continues to grow, the majority of studies examine decisions made to maximize monetary earnings or points. It is not clear whether these results generalize to other types of rewards. To investigate this, we examined adult age differences in 92 healthy participants aged 22 to 83. Participants completed 9 hypothetical discounting tasks, which included 3 types of discounting factors (time, probability, effort) across 3 reward domains (monetary, social, health). Participants made choices between a smaller magnitude reward with a shorter time delay/higher probability/lower level of physical effort required and a larger magnitude reward with a longer time delay/lower probability/higher level of physical effort required. Older compared with younger individuals were more likely to choose options that involved shorter time delays or higher probabilities of experiencing an interaction with a close social partner or receiving health benefits from a hypothetical drug. These findings suggest that older adults may be more motivated than young adults to obtain social and health rewards immediately and with certainty. (PsycINFO Database Record
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Personality traits predicting quality of life and overall functioning in schizophrenia.
Schizophrenia research (2017)
Ridgewell C, Blackford JU, McHugo M, Heckers S.
Personality traits predicting quality of life and overall functioning in schizophrenia.
Schizophr Res.
2017 Apr;
182:19-23.
Abstract: Clinical symptoms and sociodemographic variables predict level of functioning and quality of life in patients with schizophrenia. However, few studies have examined the effect of personality traits on quality of life and overall functioning in schizophrenia. Personality traits are premorbid to illness and may predict the way patients experience schizophrenia. The aim of this study was to examine the individual and additive effects of two core personality traits-neuroticism and extraversion-on quality of life and functioning.
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The associations between multisensory temporal processing and symptoms of schizophrenia.
Schizophrenia research (2017)
Stevenson RA, Park S, Cochran C, McIntosh LG, Noel JP, Barense MD, Ferber S, Wallace MT.
The associations between multisensory temporal processing and symptoms of schizophrenia.
Schizophr Res.
2017 Jan;
179:97-103.
Abstract: Recent neurobiological accounts of schizophrenia have included an emphasis on changes in sensory processing. These sensory and perceptual deficits can have a cascading effect onto higher-level cognitive processes and clinical symptoms. One form of sensory dysfunction that has been consistently observed in schizophrenia is altered temporal processing. In this study, we investigated temporal processing within and across the auditory and visual modalities in individuals with schizophrenia (SCZ) and age-matched healthy controls. Individuals with SCZ showed auditory and visual temporal processing abnormalities, as well as multisensory temporal processing dysfunction that extended beyond that attributable to unisensory processing dysfunction. Most importantly, these multisensory temporal deficits were associated with the severity of hallucinations. This link between atypical multisensory temporal perception and clinical symptomatology suggests that clinical symptoms of schizophrenia may be at least partly a result of cascading effects from (multi)sensory disturbances. These results are discussed in terms of underlying neural bases and the possible implications for remediation.
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Effects of early life stress on depression, cognitive performance and brain morphology.
Psychological medicine (2017)
Saleh A, Potter GG, McQuoid DR, Boyd B, Turner R, MacFall JR, Taylor WD.
Effects of early life stress on depression, cognitive performance and brain morphology.
Psychol Med.
2017 Jan;
47(1):171-181.
Abstract: Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure.
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Radiological Image Traits Predictive of Cancer Status in Pulmonary Nodules.
Clinical cancer research : an official journal of the American Association for Cancer Research (2017)
Liu Y, Balagurunathan Y, Atwater T, Antic S, Li Q, Walker RC, Smith GT, Massion PP, Schabath MB, Gillies RJ.
Radiological Image Traits Predictive of Cancer Status in Pulmonary Nodules.
Clin Cancer Res.
2017 Mar 15;
23(6):1442-1449.
Abstract: We propose a systematic methodology to quantify incidentally identified pulmonary nodules based on observed radiological traits (semantics) quantified on a point scale and a machine-learning method using these data to predict cancer status. We investigated 172 patients who had low-dose CT images, with 102 and 70 patients grouped into training and validation cohorts, respectively. On the images, 24 radiological traits were systematically scored and a linear classifier was built to relate the traits to malignant status. The model was formed both with and without size descriptors to remove bias due to nodule size. The multivariate pairs formed on the training set were tested on an independent validation data set to evaluate their performance. The best 4-feature set that included a size measurement (set 1), was short axis, contour, concavity, and texture, which had an area under the receiver operator characteristic curve (AUROC) of 0.88 (accuracy = 81%, sensitivity = 76.2%, specificity = 91.7%). If size measures were excluded, the four best features (set 2) were location, fissure attachment, lobulation, and spiculation, which had an AUROC of 0.83 (accuracy = 73.2%, sensitivity = 73.8%, specificity = 81.7%) in predicting malignancy in primary nodules. The validation test AUROC was 0.8 (accuracy = 74.3%, sensitivity = 66.7%, specificity = 75.6%) and 0.74 (accuracy = 71.4%, sensitivity = 61.9%, specificity = 75.5%) for sets 1 and 2, respectively. Radiological image traits are useful in predicting malignancy in lung nodules. These semantic traits can be used in combination with size-based measures to enhance prediction accuracy and reduce false-positives. .
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Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study.
American journal of preventive medicine (2017)
Giuse NB, Koonce TY, Kusnoor SV, Prather AA, Gottlieb LM, Huang LC, Phillips SE, Shyr Y, Adler NE, Stead WW.
Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study.
Am J Prev Med.
2017 Feb;
52(2):199-206.
Abstract: Social and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order.
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Neither vaginal nor buccal administration of 800 μg misoprostol alters mucosal and systemic immune activation or the cervicovaginal microbiome: a pilot study.
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception (2016)
Kalams SA, Rogers LM, Smith RM, Barnett L, Crumbo K, Sumner S, Prashad N, Rybczyk K, Milne G, Dowd SE, Chong E, Winikoff B, Aronoff DM.
Neither vaginal nor buccal administration of 800 μg misoprostol alters mucosal and systemic immune activation or the cervicovaginal microbiome: a pilot study.
Eur J Contracept Reprod Health Care.
2016 Dec;
21(6):436-442.
Abstract: The aim of the study was to assess the extent to which misoprostol alters mucosal or systemic immune responses following either buccal or vaginal administration.
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Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia.
Pain medicine (Malden, Mass.) (2017)
Merriwether EN, Rakel BA, Zimmerman MB, Dailey DL, Vance CGT, Darghosian L, Golchha M, Geasland KM, Chimenti R, Crofford LJ, Sluka KA.
Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia.
Pain Med.
2017 Aug 1;
18(8):1485-1495.
Abstract: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to standardize measurement of clinically relevant patient-reported outcomes. This study evaluated the reliability and construct validity of select PROMIS static short-form (SF) instruments in women with fibromyalgia.
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Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.
Genetics in medicine : official journal of the American College of Medical Genetics (2017)
Brothers KB, East KM, Kelley WV, Wright MF, Westbrook MJ, Rich CA, Bowling KM, Lose EJ, Bebin EM, Simmons S, Myers JA, Barsh G, Myers RM, Cooper GM, Pulley JM, Rothstein MA, Clayton EW.
Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.
Genet Med.
2017 Mar;
19(3):337-344.
Abstract: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences.
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Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.
JAMA psychiatry (2016)
Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, Brian J, Arnold LE, Capano L, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Hadjiyannakis S, Peleg N, Odrobina D, McAuliffe-Bellin S, Zakroysky P, Marler S, Wagner A, Wo.
Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.
JAMA Psychiatry.
2016 Sep 1;
73(9):928-37.
Abstract: Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use.
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Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.
Hypertension (Dallas, Tex. : 1979) (2016)
Gamboa A, Figueroa R, Paranjape SY, Farley G, Diedrich A, Biaggioni I.
Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.
Hypertension.
2016 Oct;
68(4):1004-10.
Abstract: Impaired nitric oxide (NO) vasodilation (endothelial dysfunction) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30<body mass index<40 kg/m(2)). Acetylcholine and sodium nitroprusside were given at equipotent doses (10, 30, and 50 μg/min and 1, 2, and 3 μg/min, respectively) to 14 obese subjects (49±3.6 years, 34±1 kg/m(2), 165/94±7/6 mm Hg), on separate occasions 1 month apart, randomly assigned. Autonomic blockade increased basal forearm blood flow (from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute, P=0.078). As expected, NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside, but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine, P<0.05. In contrast, forearm blood flow responses to acetylcholine were restored by autonomic blockade and were no longer different to nitroprusside (from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9, respectively, P=0.58). Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target.
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Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV.
AIDS research and human retroviruses (2017)
Grome HN, Barnett L, Hagar CC, Harrison DG, Kalams SA, Koethe JR.
Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV.
AIDS Res Hum Retroviruses.
2017 Feb;
33(2):181-186.
Abstract: HIV-infected individuals are at increased risk of cardiovascular disease (CVD), but the arterial vascular functions affected by persistent innate and cellular immune activation are not well described. We assessed the relationship between immunologic and vascular parameters in 70 HIV-infected adults on efavirenz, tenofovir, and emtricitabine with more than 2 years of virologic suppression and no history of CVD. We measured brachial artery flow-mediated dilation (FMD) using ultrasound and circulating intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by multiple immunoassay. We also measured circulating naive (CD45ROCCR7CD27), activated (CD38 and CD38DR), exhausted (PD1), senescent (CD57), and memory (CD45RO) CD4 and CD8 T cell subsets by flow cytometry, and macrophage activation markers by ELISA and multiple immunoassay. Regression models were adjusted for age, sex, smoking, duration of antiretroviral therapy (ART), and body mass index. Median age was 45 years (IQR 39, 50), median CD4 count 701 cells/μl (IQR 540, 954), and 43% were female. Lower brachial FMD was associated with a higher percentage of activated CD8 T cells (p < .01), but not associated with macrophage activation. In contrast, higher ICAM-1 and VCAM-1 were associated with sCD163 (p < = .01 for both), macrophage inflammatory protein-1α (p < = .02 for both), and sCD14 (p = .01 for ICAM-1 only). These findings are consistent with the hypothesis that circulating CD8 T cell activation may impair arterial smooth muscle relaxation, while macrophage activation has a role in the expression of endothelial cell proteins involved in immune cell translocation. Both innate and cellular immune activation appear to promote arterial vascular disease in HIV-infected persons on ART using differing mechanisms.
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Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder.
Journal of neurodevelopmental disorders (2016)
Taylor JL, Gotham KO.
Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder.
J Neurodev Disord.
2016;
8:28.
Abstract: Co-occurring mood and anxiety symptomatology is commonly observed among youth with autism spectrum disorders (ASD) during adolescence and adulthood. Yet, little is known about the factors that might predispose youth with ASD to mood and anxiety problems. In this study, we focus on the role of cumulative stressful life events and trauma in co-occurring psychopathology among youth with ASD who are preparing to exit high school. Specifically, we examined the distribution of cumulative life events and traumatic experiences and their relations with mood and anxiety symptomatology.
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Temporal summation to thermal stimuli is elevated in women with overactive bladder syndrome.
Neurourology and urodynamics (2017)
Reynolds WS, Brown ET, Danford J, Kaufman M, Wein A, Dmochowski R, Bruehl S.
Temporal summation to thermal stimuli is elevated in women with overactive bladder syndrome.
Neurourol Urodyn.
2017 Apr;
36(4):1108-1112.
Abstract: This study sought to provide a preliminary assessment of whether spinally mediated afferent hyperactivity (i.e., central sensitization) might contribute to manifestations of overactive bladder syndrome (OAB) in women as indexed by elevated temporal summation of evoked heat pain stimuli.
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Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients.
BMC nutrition (2016)
Denny GB, Deger SM, Chen G, Bian A, Sha F, Booker C, Kesler JT, David S, Ellis CD, Ikizler TA.
Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients.
BMC Nutr.
2016;
2:.
Abstract: Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients.
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Biopsychosocial Approaches to Men's Health Disparities Research and Policy.
Behavioral medicine (Washington, D.C.) (2016)
Griffith DM.
Biopsychosocial Approaches to Men's Health Disparities Research and Policy.
Behav Med.
2016 Jul-Sep;
42(3):211-5.
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Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.
Medicine (2016)
Koethe JR, Jenkins CA, Petucci C, Culver J, Shepherd BE, Sterling TR.
Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.
Medicine (Baltimore).
2016 May;
95(19):e3634.
Abstract: In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50 copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P < 0.05 for both) compared with men but had similar CD4+ count (median 701 cells/μL), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3 kg/m). However, women had higher insulin sensitivity compared with men (P < 0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P < 0.01 for all), and lower C3 and C5 acylcarnitines (P < 0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not significantly differ according to HIV-status.HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection.
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Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.
Metabolism: clinical and experimental (2016)
Shah SS, Ramirez CE, Powers AC, Yu C, Shibao CA, Luther JM.
Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.
Metabolism.
2016 Jun;
65(6):835-42.
Abstract: Metabolic syndrome is associated with insulin resistance and increased future risk of type 2 diabetes. This study investigates the relationship between insulin secretion, insulin resistance and individual metabolic syndrome components in subjects without a prior diagnosis of diabetes.
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Contact heat sensitivity and reports of unpleasantness in communicative people with mild to moderate cognitive impairment in Alzheimer's disease: a cross-sectional study.
BMC medicine (2016)
Monroe TB, Gibson SJ, Bruehl SP, Gore JC, Dietrich MS, Newhouse P, Atalla S, Cowan RL.
Contact heat sensitivity and reports of unpleasantness in communicative people with mild to moderate cognitive impairment in Alzheimer's disease: a cross-sectional study.
BMC Med.
2016 May 10;
14:74.
Abstract: Compared to healthy controls, people with Alzheimer's disease (AD) have been shown to receive less pain medication and report pain less frequently. It is unknown if these findings reflect less perceived pain in AD, an inability to recognize pain, or an inability to communicate pain.
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Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease.
Physiological reports (2016)
Gamboa JL, Billings FT 4th, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ 2nd, Himmelfarb J, Ikizler TA, Brown NJ.
Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease.
Physiol Rep.
2016 May;
4(9):.
Abstract: Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2-isoprostanes in 208 subjects divided into three groups: non-CKD (eGFR>60 mL/min), CKD stage 3-4 (eGFR 60-15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non-CKD (6.48, 95% CI 4.49-8.46), CKD stage 3-4 (3.30, 95% CI 0.85-5.75, P = 0.048 vs. non-CKD), and CKD stage 5 (1.93, 95% CI 0.27-3.59, P = 0.001 vs. non-CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76-95.36) compared to patients with non-CKD (median 49.95 pg/mL, IQR 27.88-83.46, P = 0.001), whereas F2-isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages.
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A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition.
The Journal of clinical endocrinology and metabolism (2016)
Shibao CA, Celedonio JE, Ramirez CE, Love-Gregory L, Arnold AC, Choi L, Okamoto LE, Gamboa A, Biaggioni I, Abumrad NN, Abumrad NA.
A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition.
J Clin Endocrinol Metab.
2016 Jul;
101(7):2751-8.
Abstract: The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction.
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A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity.
Obesity (Silver Spring, Md.) (2016)
Lomenick JP, Buchowski MS, Shoemaker AH.
A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity.
Obesity (Silver Spring).
2016 Jun;
24(6):1222-5.
Abstract: Hypothalamic obesity (HO) is a common complication of hypothalamic tumors, and effective therapies are lacking. The objective of this pilot study was to investigate changes in body weight before and during treatment with exenatide.
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Improving Cerebellar Segmentation with Statistical Fusion.
Proceedings of SPIE--the International Society for Optical Engineering (2016)
Plassard AJ, Yang Z, Rane S, Prince JL, Claassen DO, Landman BA.
Improving Cerebellar Segmentation with Statistical Fusion.
Proc SPIE Int Soc Opt Eng.
2016 Feb 27;
9784:.
Abstract: The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multi-atlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non-Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.
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Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites.
Pharmacology research & perspectives (2016)
Gamboa JL, Devin JK, Ramirez CE, Yu C, Nian H, Lee RH, Brown NJ.
Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites.
Pharmacol Res Perspect.
2016 Apr;
4(2):e00221.
Abstract: A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti-thrombotic prostacyclin. This study tested the hypothesis that extended-release aspirin (NHP-554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate-release aspirin (ASA). Thirty-six healthy subjects were randomized to NHP-554C or ASA groups. Within each group, subjects were randomized to 5-day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2-week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11-dehydro-thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3-dinor-6-keto-PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP-554C 81 mg/d and 162.5 mg/d reduced 11-dehydro-thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3-dinor-6-keto-PGF1α 13.4% and 18.5%, respectively. NHP-554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP-554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3-dinor-6-keto-PGF1α. Nevertheless, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α responses to bradykinin were statistically similar during ASA and NHP-554C. In conclusion, at doses of 81 and 162.5 mg/d immediate- and extended-release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin-stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP-554C.
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Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health.
Annual review of public health (2016)
Gilbert KL, Ray R, Siddiqi A, Shetty S, Baker EA, Elder K, Griffith DM.
Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health.
Annu Rev Public Health.
2016;
37:295-311.
Abstract: Over the past two decades, there has been growing interest in improving black men's health and the health disparities affecting them. Yet, the health of black men consistently ranks lowest across nearly all groups in the United States. Evidence on the health and social causes of morbidity and mortality among black men has been narrowly concentrated on public health problems (e.g., violence, prostate cancer, and HIV/AIDS) and determinants of health (e.g., education and male gender socialization). This limited focus omits age-specific leading causes of death and other social determinants of health, such as discrimination, segregation, access to health care, employment, and income. This review discusses the leading causes of death for black men and the associated risk factors, as well as identifies gaps in the literature and presents a racialized and gendered framework to guide efforts to address the persistent inequities in health affecting black men.
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Perceived function and physical performance are associated with pain and fatigue in women with fibromyalgia.
Arthritis research & therapy (2016)
Dailey DL, Frey Law LA, Vance CG, Rakel BA, Merriwether EN, Darghosian L, Golchha M, Geasland KM, Spitz R, Crofford LJ, Sluka KA.
Perceived function and physical performance are associated with pain and fatigue in women with fibromyalgia.
Arthritis Res Ther.
2016 Mar 16;
18:68.
Abstract: Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue and associated with significant impairment in perceived function and reduced physical performance. The purpose of this study was to determine the degree to which pain and fatigue are associated with perceived function and physical performance in women with fibromyalgia.
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The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview.
Journal of Alzheimer's disease : JAD (2016)
Jefferson AL, Gifford KA, Acosta LM, Bell SP, Donahue MJ, Davis LT, Gottlieb J, Gupta DK, Hohman TJ, Lane EM, Libon DJ, Mendes LA, Niswender K, Pechman KR, Rane S, Ruberg FL, Su YR, Zetterberg H, Liu D.
The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview.
J Alzheimers Dis.
2016 Mar 8;
52(2):539-59.
Abstract: Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities.
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Differences in Perceptions of the Food Environment Between African American Men Who Did and Did Not Consume Recommended Levels of Fruits and Vegetables.
Health education & behavior : the official publication of the Society for Public Health Education (2016)
Griffith DM, Cornish EK, McKissic SA, Dean DA.
Differences in Perceptions of the Food Environment Between African American Men Who Did and Did Not Consume Recommended Levels of Fruits and Vegetables.
Health Educ Behav.
2016 Dec;
43(6):648-655.
Abstract: African American men have high rates of chronic disease morbidity and mortality associated with their low rates of fruit and vegetable consumption. In an effort to inform tailored behavioral interventions for this demographic, we sought to assess if men with healthier eating practices viewed their environment differently than those who ate less healthy. We segmented participants into high/low healthy eating categories based on the daily fruit and vegetable serving recommendations from the U.S. Department of Agriculture to determine if differences among environmental and social barriers were associated with different healthy eating patterns. We found key differences between men who consumed the recommended amount of fruits and vegetables (five or more servings/day, high healthy eating) and men who did not (low healthy eating). Men who consumed recommended levels of fruits and vegetables found eating healthy to be easy, and they described how they were able to overcome barriers such as the cost of healthy food, their limited knowledge of nutrition guidelines, and their lack of willpower to make healthier food choices. Men with healthier eating practices also identified individuals, plans, and resources they used or could use to help them have healthier eating practices. Conversely, men who were not eating recommended levels of fruits and vegetables also found eating healthy to be easy; however, they identified barriers limiting their access and did not articulate strategies to overcome these perceived barriers. Many of these men also indicated that they did not have social support to help them engage in healthier eating practices. These findings highlight the need to understand how African American men's conceptualization of environmental resources and social supports relate to their eating practices.
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Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis.
Arthritis & rheumatology (Hoboken, N.J.) (2016)
Munters LA, Loell I, Ossipova E, Raouf J, Dastmalchi M, Lindroos E, Chen YW, Esbjörnsson M, Korotkova M, Alexanderson H, Nagaraju K, Crofford LJ, Jakobsson PJ, Lundberg IE.
Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis.
Arthritis Rheumatol.
2016 Jul;
68(7):1738-50.
Abstract: Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM.
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Interactions between space and effectiveness in human multisensory performance.
Neuropsychologia (2016)
Nidiffer AR, Stevenson RA, Krueger Fister J, Barnett ZP, Wallace MT.
Interactions between space and effectiveness in human multisensory performance.
Neuropsychologia.
2016 Jul 29;
88:83-91.
Abstract: Several stimulus factors are important in multisensory integration, including the spatial and temporal relationships of the paired stimuli as well as their effectiveness. Changes in these factors have been shown to dramatically change the nature and magnitude of multisensory interactions. Typically, these factors are considered in isolation, although there is a growing appreciation for the fact that they are likely to be strongly interrelated. Here, we examined interactions between two of these factors - spatial location and effectiveness - in dictating performance in the localization of an audiovisual target. A psychophysical experiment was conducted in which participants reported the perceived location of visual flashes and auditory noise bursts presented alone and in combination. Stimuli were presented at four spatial locations relative to fixation (0°, 30°, 60°, 90°) and at two intensity levels (high, low). Multisensory combinations were always spatially coincident and of the matching intensity (high-high or low-low). In responding to visual stimuli alone, localization accuracy decreased and response times (RTs) increased as stimuli were presented at more eccentric locations. In responding to auditory stimuli, performance was poorest at the 30° and 60° locations. For both visual and auditory stimuli, accuracy was greater and RTs were faster for more intense stimuli. For responses to visual-auditory stimulus combinations, performance enhancements were found at locations in which the unisensory performance was lowest, results concordant with the concept of inverse effectiveness. RTs for these multisensory presentations frequently violated race-model predictions, implying integration of these inputs, and a significant location-by-intensity interaction was observed. Performance gains under multisensory conditions were larger as stimuli were positioned at more peripheral locations, and this increase was most pronounced for the low-intensity conditions. These results provide strong support that the effects of stimulus location and effectiveness on multisensory integration are interdependent, with both contributing to the overall effectiveness of the stimuli in driving the resultant multisensory response.
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Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.
The Journal of clinical endocrinology and metabolism (2015)
Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA.
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.
J Clin Endocrinol Metab.
2015 Dec;
100(12):4533-40.
Abstract: Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.
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Time-Course Analysis of Flow Mediated Dilation for the Evaluation of Endothelial Function After a High-Fat Meal in African Americans.
Journal of the American Heart Association (2015)
Marinos A, Celedonio JE, Ramirez CE, Gottlieb J, Gamboa A, Hui N, Yu C, Stein CM, Biaggioni I, Shibao CA.
Time-Course Analysis of Flow Mediated Dilation for the Evaluation of Endothelial Function After a High-Fat Meal in African Americans.
J Am Heart Assoc.
2015 Nov 5;
4(11):.
Abstract: Flow-mediated dilation (FMD) is used to assess endothelial function through changes in vascular diameter after hyperemia. High-fat meal (HFM) has been shown to induce endothelial dysfunction; recent studies, however, reported conflicting results in obese African American women (AAW). Differences in the method used to analyze FMD may explain these discrepancies.
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Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study.
BMC nephrology (2015)
Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA.
Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study.
BMC Nephrol.
2015 Oct 22;
16:167.
Abstract: Endothelial dysfunction occurs in patients with end-stage renal disease (ESRD) and is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) contributes to endothelial dysfunction in ESRD. In the general population, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease ADMA levels, but no study has compared the effect of these drugs in patients with ESRD on maintenance hemodialysis (MHD).
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Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.
The Journal of infectious diseases (2016)
Walsh SR, Moodie Z, Fiore-Gartland AJ, Morgan C, Wilck MB, Hammer SM, Buchbinder SP, Kalams SA, Goepfert PA, Mulligan MJ, Keefer MC, Baden LR, Swann EM, Grant S, Ahmed H, Li F, Hertz T, Self SG, Friedrich D, Frahm N, Liao HX, Montefiori DC, Tomaras GD, Mc.
Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.
J Infect Dis.
2016 Feb 15;
213(4):541-50.
Abstract: Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both.
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Evaluation of the F2R IVS-14A/T PAR1 polymorphism with subsequent cardiovascular events and bleeding in patients who have undergone percutaneous coronary intervention.
Journal of thrombosis and thrombolysis (2016)
Friedman EA, Texeira L, Delaney J, Weeke PE, Lynch DR Jr, Kasasbeh E, Song Y, Harrell FE Jr, Denny JC, Hamm HE, Roden DM, Cleator JH.
Evaluation of the F2R IVS-14A/T PAR1 polymorphism with subsequent cardiovascular events and bleeding in patients who have undergone percutaneous coronary intervention.
J Thromb Thrombolysis.
2016 May;
41(4):656-62.
Abstract: Abnormal platelet reactivity is associated with recurrent ischemia and bleeding following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR1), encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR1 receptor density and function. We hypothesized that carriers of the T allele, who have been shown to have decreased platelet reactivity, would be at lower risk for thrombotic events, but higher risk for bleeding following PCI. Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record, we studied 660 patients who underwent PCI for unstable or stable coronary artery disease. Primary outcome measures were major adverse cardiovascular events (MACE, composite of revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research Consortium scale) over 24 months. The minor allele (T) frequency was 14.8 %. There were no genotypic differences in the frequency of MACE (33.7, 28.8, and 31.6 % for A/A, A/T, and T/T respectively, P = 0.50) or bleeding (15.7, 14.7, and 18.8 % for A/A, A/T, and T/T respectively, P = 0.90). In a Cox regression model, fully adjusted for age, race, sex, BMI, and smoking status, carrying a T allele was not associated with MACE (HR 1.19, 95 % CI 0.89-1.59, P = 0.23) or bleeding (HR 0.73, 95 % CI 0.37-1.4, P = 0.34). In conclusion, in our population, F2R IVS-14 PAR1 variability does not affect risk of MACE or bleeding following PCI.
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Secretory IgA from submucosal glands does not compensate for its airway surface deficiency in chronic obstructive pulmonary disease.
Virchows Archiv : an international journal of pathology (2015)
Du RH, Richmond BW, Blackwell TS Jr, Cates JM, Massion PP, Ware LB, Lee JW, Kononov AV, Lawson WE, Blackwell TS, Polosukhin VV.
Secretory IgA from submucosal glands does not compensate for its airway surface deficiency in chronic obstructive pulmonary disease.
Virchows Arch.
2015 Dec;
467(6):657-665.
Abstract: Secretory immunoglobulin A (SIgA) reaches the airway lumen by local transcytosis across airway epithelial cells or with tracheobronchial submucosal gland secretions. In chronic obstructive pulmonary disease (COPD), deficiency of SIgA on the airway surface has been reported. However, reduction of SIgA levels in sputum and bronchoalveolar lavage (BAL) fluid has not been consistently observed. To explain this discrepancy, we analyzed BAL fluid and lung tissue from patients with COPD and control subjects. Immunohistochemical analysis of large and small airways of COPD patients showed that MUC5AC is the predominant mucin expressed by airway epithelial cells, whereas MUC5B is expressed in submucosal glands of large airways. Dual immunostaining with anti-IgA and anti-MUC5B antibodies showed reduction of IgA on the airway surface as well as accumulation of IgA within MUC5B-positive luminal mucus plugs, suggesting that luminal SIgA originates from submucosal glands in COPD patients. We found that the concentration of SIgA in BAL is inversely correlated with forced expiratory volume in 1 s (FEV) in COPD, but that the ratio of SIgA/MUC5B is a better predictor of FEV, particularly in patients with moderate COPD. Together, these findings suggest that SIgA production by submucosal glands, which are expanded in COPD, is insufficient to compensate for reduced SIgA transcytosis by airway epithelial cells. Localized SIgA deficiency on the surface of small airways is associated with COPD progression and represents a potential new therapeutic target in COPD.
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Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder.
Journal of autism and developmental disorders (2016)
Corbett BA, Key AP, Qualls L, Fecteau S, Newsom C, Coke C, Yoder P.
Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder.
J Autism Dev Disord.
2016 Feb;
46(2):658-72.
Abstract: The efficacy of a peer-mediated, theatre-based intervention on social competence in participants with autism spectrum disorder (ASD) was tested. Thirty 8-to-14 year-olds with ASD were randomly assigned to the treatment (n = 17) or a wait-list control (n = 13) group. Immediately after treatment, group effects were seen on social ability, (d = .77), communication symptoms (d = -.86), group play with toys in the company of peers (d = .77), immediate memory of faces as measured by neuropsychological (d = .75) and ERP methods (d = .93), delayed memory for faces (d = .98), and theory of mind (d = .99). At the 2 month follow-up period, group effects were detected on communication symptoms (d = .82). The results of this pilot clinical trial provide initial support for the efficacy of the theatre-based intervention.
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The metabolic and cardiovascular consequences of obesity in persons with HIV on long-term antiretroviral therapy.
AIDS (London, England) (2016)
Koethe JR, Grome H, Jenkins CA, Kalams SA, Sterling TR.
The metabolic and cardiovascular consequences of obesity in persons with HIV on long-term antiretroviral therapy.
AIDS.
2016 Jan 2;
30(1):83-91.
Abstract: This study assessed the effect of obesity on metabolic and cardiovascular disease risk factors in HIV-infected adults on antiretroviral therapy with sustained virologic suppression.
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Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval.
PloS one (2015)
Smith GT, Rahman AR, Li M, Moore B, Gietema H, Veronesi G, Massion PP, Walker RC.
Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval.
PLoS One.
2015;
10(9):e0138144.
Abstract: To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up.
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Temporal patterns, heterogeneity, and stability of diurnal cortisol rhythms in children with autism spectrum disorder.
Psychoneuroendocrinology (2015)
Tomarken AJ, Han GT, Corbett BA.
Temporal patterns, heterogeneity, and stability of diurnal cortisol rhythms in children with autism spectrum disorder.
Psychoneuroendocrinology.
2015 Dec;
62:217-26.
Abstract: The current study used a multifaceted approach to assess whether children with ASD have a distinctive diurnal rhythm of cortisol that differentiates them from typically developing (TD) peers and whether sub-groups of ASD children can be identified with unique diurnal profiles. Salivary cortisol was sampled at four time points during the day (waking, 30-min post-waking, afternoon, and evening) across three days in a sample of 36 children with autism spectrum disorder (ASD) and 27 typically developing (TD) peers. Between-group comparisons on both mean levels and featural components of diurnal cortisol indicated elevated evening cortisol and a dampened linear decline across the day in the ASD group. No differences were evident on the cortisol awakening response (CAR). Group-based trajectory modeling indicated that a subgroup (25%) of ASD children demonstrated an attenuated linear decline while the cortisol trajectory of the second subgroup was indistinguishable from that of the TD group. Intraclass correlations indicated that, when aggregated across days, cortisol measures were generally stable over the interval assessed. There were few significant relations between cortisol measures or sub-groups and measures of stress, temperament, and symptoms. Results encourage follow-up studies to investigate the functional significance, heterogeneity and longer-term stability of diurnal cortisol profiles in children with ASD.
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Psychological aspects of chronic musculoskeletal pain.
Best practice & research. Clinical rheumatology (2015)
Crofford LJ.
Psychological aspects of chronic musculoskeletal pain.
Best Pract Res Clin Rheumatol.
2015 Feb;
29(1):147-55.
Abstract: Chronic musculoskeletal pain, by its very nature, is associated with negative emotions and psychological distress. There are individual differences in personality, coping skills, behavioral adaptation, and social support that dramatically alter the psychological outcomes of patients with chronic pain. Patients who have an aspect of central pain amplification associated with mechanical or inflammatory pain and patients with fibromyalgia (FM) are likely to exhibit higher levels of psychological distress and illness behaviors. This manuscript discusses several different constructs for the association between chronic pain, central pain amplification, and psychological distress. The first key question addresses mechanisms shared in common between chronic pain and mood disorders, including the individual factors that influence psychological comorbidity, and the second addresses how pain affects mood and vice versa. Finally, the utility of cognitive behavioral approaches in the management of chronic pain symptoms is discussed.
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Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.
The Journal of allergy and clinical immunology (2015)
Newcomb DC, Cephus JY, Boswell MG, Fahrenholz JM, Langley EW, Feldman AS, Zhou W, Dulek DE, Goleniewska K, Woodward KB, Sevin CM, Hamilton RG, Kolls JK, Peebles RS Jr.
Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.
J Allergy Clin Immunol.
2015 Oct;
136(4):1025-34.e11.
Abstract: Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA.
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Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study.
BMJ (Clinical research ed.) (2015)
Xian Y, Wu J, O'Brien EC, Fonarow GC, Olson DM, Schwamm LH, Bhatt DL, Smith EE, Suter RE, Hannah D, Lindholm B, Maisch L, Greiner MA, Lytle BL, Pencina MJ, Peterson ED, Hernandez AF.
Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study.
BMJ.
2015 Jul 31;
351:h3786.
Abstract: To examine the association between warfarin treatment and longitudinal outcomes after ischemic stroke in patients with atrial fibrillation in community practice.
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Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.
Current neurology and neuroscience reports (2015)
Garland EM, Celedonio JE, Raj SR.
Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.
Curr Neurol Neurosci Rep.
2015 Sep;
15(9):60.
Abstract: Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a "final common pathway" for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support.
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Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research: Implementing the patient-driven research paradigm to aid decision making in stroke care.
American heart journal (2015)
Xian Y, O'Brien EC, Fonarow GC, Olson DM, Schwamm LH, Hannah D, Lindholm B, Maisch L, Lytle BL, Greiner MA, Wu J, Peterson ED, Pencina MJ, Hernandez AF.
Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research: Implementing the patient-driven research paradigm to aid decision making in stroke care.
Am Heart J.
2015 Jul;
170(1):36-45, 45.e1-11.
Abstract: Stroke is common and costly, annually depriving the lives and well-being of 800,000 Americans. Despite demonstrated efficacy in clinical trials, questions remain about the safety and clinical effectiveness of various treatment options given patient characteristics, conditions, preferences, and their desired outcomes.
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Widespread white matter but focal gray matter alterations in depressed individuals with thoughts of death.
Progress in neuro-psychopharmacology & biological psychiatry (2015)
Taylor WD, Boyd B, McQuoid DR, Kudra K, Saleh A, MacFall JR.
Widespread white matter but focal gray matter alterations in depressed individuals with thoughts of death.
Prog Neuropsychopharmacol Biol Psychiatry.
2015 Oct 1;
62:22-8.
Abstract: Past work demonstrates that depressed individuals with suicidal thoughts or behaviors exhibit specific neuroanatomical alterations. This may represent a distinct phenotype characterized by specific findings on neuroimaging, but it is unclear if these findings extend to individuals with milder thoughts of death. We examined this question in outpatients with recurrent Major Depressive Disorder not receiving antidepressant treatment.
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Multi-Atlas Segmentation for Abdominal Organs with Gaussian Mixture Models.
Proceedings of SPIE--the International Society for Optical Engineering (2015)
Burke RP, Xu Z, Lee CP, Baucom RB, Poulose BK, Abramson RG, Landman BA.
Multi-Atlas Segmentation for Abdominal Organs with Gaussian Mixture Models.
Proc SPIE Int Soc Opt Eng.
2015 Mar 17;
9417:.
Abstract: Abdominal organ segmentation with clinically acquired computed tomography (CT) is drawing increasing interest in the medical imaging community. Gaussian mixture models (GMM) have been extensively used through medical segmentation, most notably in the brain for cerebrospinal fluid/gray matter/white matter differentiation. Because abdominal CT exhibit strong localized intensity characteristics, GMM have recently been incorporated in multi-stage abdominal segmentation algorithms. In the context of variable abdominal anatomy and rich algorithms, it is difficult to assess the marginal contribution of GMM. Herein, we characterize the efficacy of an framework that integrates GMM of organ-wise intensity likelihood with spatial priors from multiple target-specific registered labels. In our study, we first manually labeled 100 CT images. Then, we assigned 40 images to use as training data for constructing target-specific spatial priors and intensity likelihoods. The remaining 60 images were evaluated as test targets for segmenting 12 abdominal organs. The overlap between the true and the automatic segmentations was measured by Dice similarity coefficient (DSC). A median improvement of 145% was achieved by integrating the GMM intensity likelihood against the specific spatial prior. The proposed framework opens the opportunities for abdominal organ segmentation by efficiently using both the spatial and appearance information from the atlases, and creates a benchmark for large-scale automatic abdominal segmentation.
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Toward Content Based Image Retrieval with Deep Convolutional Neural Networks.
Proceedings of SPIE--the International Society for Optical Engineering (2015)
Sklan JE, Plassard AJ, Fabbri D, Landman BA.
Toward Content Based Image Retrieval with Deep Convolutional Neural Networks.
Proc SPIE Int Soc Opt Eng.
2015 Mar 19;
9417:.
Abstract: Content-based image retrieval (CBIR) offers the potential to identify similar case histories, understand rare disorders, and eventually, improve patient care. Recent advances in database capacity, algorithm efficiency, and deep Convolutional Neural Networks (dCNN), a machine learning technique, have enabled great CBIR success for general photographic images. Here, we investigate applying the leading ImageNet CBIR technique to clinically acquired medical images captured by the Vanderbilt Medical Center. Briefly, we (1) constructed a dCNN with four hidden layers, reducing dimensionality of an input scaled to 128×128 to an output encoded layer of 4×384, (2) trained the network using back-propagation 1 million random magnetic resonance (MR) and computed tomography (CT) images, (3) labeled an independent set of 2100 images, and (4) evaluated classifiers on the projection of the labeled images into manifold space. Quantitative results were disappointing (averaging a true positive rate of only 20%); however, the data suggest that improvements would be possible with more evenly distributed sampling across labels and potential re-grouping of label structures. This prelimainry effort at automated classification of medical images with ImageNet is promising, but shows that more work is needed beyond direct adaptation of existing techniques.
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Revealing Latent Value of Clinically Acquired CTs of Traumatic Brain Injury Through Multi-Atlas Segmentation in a Retrospective Study of 1,003 with External Cross-Validation.
Proceedings of SPIE--the International Society for Optical Engineering (2015)
Plassard AJ, Kelly PD, Asman AJ, Kang H, Patel MB, Landman BA.
Revealing Latent Value of Clinically Acquired CTs of Traumatic Brain Injury Through Multi-Atlas Segmentation in a Retrospective Study of 1,003 with External Cross-Validation.
Proc SPIE Int Soc Opt Eng.
2015 Mar 20;
9413:.
Abstract: Medical imaging plays a key role in guiding treatment of traumatic brain injury (TBI) and for diagnosing intracranial hemorrhage; most commonly rapid computed tomography (CT) imaging is performed. Outcomes for patients with TBI are variable and difficult to predict upon hospital admission. Quantitative outcome scales (e.g., the Marshall classification) have been proposed to grade TBI severity on CT, but such measures have had relatively low value in staging patients by prognosis. Herein, we examine a cohort of 1,003 subjects admitted for TBI and imaged clinically to identify potential prognostic metrics using a "big data" paradigm. For all patients, a brain scan was segmented with multi-atlas labeling, and intensity/volume/texture features were computed in a localized manner. In a 10-fold cross-validation approach, the explanatory value of the image-derived features is assessed for length of hospital stay (days), discharge disposition (five point scale from death to return home), and the Rancho Los Amigos functional outcome score (Rancho Score). Image-derived features increased the predictive R to 0.38 (from 0.18) for length of stay, to 0.51 (from 0.4) for discharge disposition, and to 0.31 (from 0.16) for Rancho Score (over models consisting only of non-imaging admission metrics, but including positive/negative radiological CT findings). This study demonstrates that high volume retrospective analysis of clinical imaging data can reveal imaging signatures with prognostic value. These targets are suited for follow-up validation and represent targets for future feature selection efforts. Moreover, the increase in prognostic value would improve staging for intervention assessment and provide more reliable guidance for patients.
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Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Antimicrobial agents and chemotherapy (2015)
Dooley KE, Savic RM, Park JG, Cramer Y, Hafner R, Hogg E, Janik J, Marzinke MA, Patterson K, Benson CA, Hovind L, Dorman SE, Haas DW, ACTG A5311 Study Team..
Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Antimicrob Agents Chemother.
2015;
59(6):3399-405.
Abstract: Rifapentine is a potent antituberculosis drug currently in phase III trials. Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration. Further, the limits of tolerability are poorly defined. The phase I multicenter trial in healthy adults described here investigated two strategies to increase rifapentine exposures: dividing the dose or giving the drug with a high-fat meal. In arm 1, rifapentine was administered at 10 mg/kg of body weight twice daily and 20 mg/kg once daily, each for 14 days, separated by a 28-day washout; the dosing sequence was randomized. In arm 2, 15 mg/kg rifapentine once daily was given with a high-fat versus a low-fat breakfast. Sampling for pharmacokinetic analysis was performed on days 1 and 14. Population pharmacokinetic analyses were performed. This trial was stopped early for poor tolerability and because of safety concerns. Of 44 subjects, 20 discontinued prematurely; 11 of these discontinued for protocol-defined toxicity (a grade 3 or higher adverse event or grade 2 or higher rifamycin hypersensitivity). Taking rifapentine with a high-fat meal increased the median steady-state area under the concentration-time curve from time zero to 24 h (AUC0-24ss) by 31% (relative standard error, 6%) compared to that obtained when the drug was taken with a low-fat breakfast. Dividing the dose increased exposures substantially (e.g., 38% with 1,500 mg/day). AUC0-24ss was uniformly higher in our study than in recent tuberculosis treatment trials, in which toxicity was rare. In conclusion, two strategies to increase rifapentine exposures, dividing the dose or giving it with a high-fat breakfast, successfully increased exposures, but toxicity was common in healthy adults. The limits of tolerability in patients with tuberculosis remain to be defined. (AIDS Clinical Trials Group study A5311 has been registered at ClinicalTrials.gov under registration no. NCT01574638.).
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Case Study: Community Engagement and Clinical Trial Success: Outreach to African American Women.
Clinical and translational science (2015)
Johnson DA, Joosten YA, Wilkins CH, Shibao CA.
Case Study: Community Engagement and Clinical Trial Success: Outreach to African American Women.
Clin Transl Sci.
2015 Aug;
8(4):388-90.
Abstract: This brief report examines how the use of community engagement principles and approaches enhanced clinical trial recruitment and retention. The Community-Engaged Research Core (CERC), a CTSA-supported resource designed to facilitate community involvement in clinical and translational research, was consulted to provide assistance with the implementation of the clinical trial, and specifically to enhance participation of the target population-African American women. CERC's key recommendations included: (1) convene a Community Engagement Studio, (2) redesign the recruitment advertisement, (3) simplify the language used to explain the scope of the study, and (4) provide transportation for participants. As a result of these interventions, a comprehensive strategy to recruit, enroll, and retain participants was formulated. After implementation of the plan by the study team, enrollment increased 78% and recruitment goals were met 16 months ahead of schedule. Participant retention and study drug adherence was 100%. We conclude that community engagement is essential to the development of an effective multifaceted plan to improve recruitment of underrepresented groups in clinical trials.
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Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.
Brain connectivity (2015)
Vega JN, Hohman TJ, Pryweller JR, Dykens EM, Thornton-Wells TA.
Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.
Brain Connect.
2015 Oct;
5(8):461-75.
Abstract: The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.
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Eating behaviors in obese children with pseudohypoparathyroidism type 1a: a cross-sectional study.
International journal of pediatric endocrinology (2014)
Wang L, Shoemaker AH.
Eating behaviors in obese children with pseudohypoparathyroidism type 1a: a cross-sectional study.
Int J Pediatr Endocrinol.
2014;
2014(1):21.
Abstract: Children with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. These children have decreased resting energy expenditure but it is unknown if hyperphagia contributes to their obesity.
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DXA-measured visceral adipose tissue predicts impaired glucose tolerance and metabolic syndrome in obese Caucasian and African-American women.
European journal of clinical nutrition (2015)
Bi X, Seabolt L, Shibao C, Buchowski M, Kang H, Keil CD, Tyree R, Silver HJ.
DXA-measured visceral adipose tissue predicts impaired glucose tolerance and metabolic syndrome in obese Caucasian and African-American women.
Eur J Clin Nutr.
2015 Mar;
69(3):329-36.
Abstract: New methods to measure visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed (1) to compare relationships of DXA-VAT, anthropometric and body composition variables with cardiometabolic risk factors in obese women; (2) to determine which variables most robustly predict impaired glucose tolerance (IGT) and metabolic syndrome (MetSx); and (3) to determine thresholds for DXA-VAT by race.
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Deficits in audiovisual speech perception in normal aging emerge at the level of whole-word recognition.
Neurobiology of aging (2015)
Stevenson RA, Nelms CE, Baum SH, Zurkovsky L, Barense MD, Newhouse PA, Wallace MT.
Deficits in audiovisual speech perception in normal aging emerge at the level of whole-word recognition.
Neurobiol Aging.
2015 Jan;
36(1):283-91.
Abstract: Over the next 2 decades, a dramatic shift in the demographics of society will take place, with a rapid growth in the population of older adults. One of the most common complaints with healthy aging is a decreased ability to successfully perceive speech, particularly in noisy environments. In such noisy environments, the presence of visual speech cues (i.e., lip movements) provide striking benefits for speech perception and comprehension, but previous research suggests that older adults gain less from such audiovisual integration than their younger peers. To determine at what processing level these behavioral differences arise in healthy-aging populations, we administered a speech-in-noise task to younger and older adults. We compared the perceptual benefits of having speech information available in both the auditory and visual modalities and examined both phoneme and whole-word recognition across varying levels of signal-to-noise ratio. For whole-word recognition, older adults relative to younger adults showed greater multisensory gains at intermediate SNRs but reduced benefit at low SNRs. By contrast, at the phoneme level both younger and older adults showed approximately equivalent increases in multisensory gain as signal-to-noise ratio decreased. Collectively, the results provide important insights into both the similarities and differences in how older and younger adults integrate auditory and visual speech cues in noisy environments and help explain some of the conflicting findings in previous studies of multisensory speech perception in healthy aging. These novel findings suggest that audiovisual processing is intact at more elementary levels of speech perception in healthy-aging populations and that deficits begin to emerge only at the more complex word-recognition level of speech signals.
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Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.
Physical therapy (2015)
Noehren B, Dailey DL, Rakel BA, Vance CG, Zimmerman MB, Crofford LJ, Sluka KA.
Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.
Phys Ther.
2015 Jan;
95(1):129-40.
Abstract: Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia.
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Examining the relationship between face processing and social interaction behavior in children with and without autism spectrum disorder.
Journal of neurodevelopmental disorders (2014)
Corbett BA, Newsom C, Key AP, Qualls LR, Edmiston EK.
Examining the relationship between face processing and social interaction behavior in children with and without autism spectrum disorder.
J Neurodev Disord.
2014;
6(1):35.
Abstract: Children with autism spectrum disorder (ASD) show impairment in reciprocal social communication, which includes deficits in social cognition and behavior. Since social cognition and social behavior are considered to be interdependent, it is valuable to examine social processes on multiple levels of analysis. Neuropsychological measures of face processing often reveal deficits in social cognition in ASD including the ability to identify and remember facial information. However, the extent to which neuropsychological measures are associated with or predictive of real-world social behavior is unclear.
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Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans.
Prostaglandins & other lipid mediators (2014)
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ.
Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans.
Prostaglandins Other Lipid Mediat.
2014 Oct;
113-115:38-44.
Abstract: Epoxyeicosatrienoic acids (EETs) protect against the development of insulin resistance in rodents. EETs are hydrolyzed to less biologically active diols by soluble epoxide hydrolase (encoded for by EPHX2). Functional variants of EPHX2 encode for enzymes with increased (Lys55Arg) or decreased (Arg287Gln) hydrolase activity. This study tested the hypothesis that variants of EPHX2 are associated with insulin sensitivity or secretion in humans. Subjects participating in metabolic phenotyping studies were genotyped. Eighty-five subjects underwent hyperglycemic clamps. There was no relationship between the Lys55Arg genotype and insulin sensitivity or secretion. In contrast, the EPHX2 287Gln variant was associated with higher insulin sensitivity index (p=0.019 controlling for body mass index and metabolic syndrome). Also, there was an interactive effect of EPHX2 Arg287Gln genotype and body mass index on insulin sensitivity index (p=0.029). There was no relationship between EPHX2 Arg287Gln genotype and acute or late-phase glucose-stimulated insulin secretion, but disposition index was higher in 287Gln carriers compared with Arg/Arg (p=0.022). Plasma EETs correlated with insulin sensitivity index (r=0.64, p=0.015 for total EETs) and were decreased in the metabolic syndrome. A genetic variant that results in decreased soluble epoxide hydrolase activity is associated with increased insulin sensitivity, as are higher EETs.
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Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm.
Journal of the American Heart Association (2014)
Devin JK, Pretorius M, Nian H, Yu C, Billings FT 4th, Brown NJ.
Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm.
J Am Heart Assoc.
2014 Aug 26;
3(4):.
Abstract: Dipeptidyl-peptidase 4 (DPP4) inhibitors improve glycemic control in patients with diabetes mellitus by preventing the degradation of glucagon-like peptide-1 (GLP-1). GLP-1 causes vasodilation in animal models but also increases sympathetic activity; the effect of GLP-1 in the human vasculature and how it is altered by DPP4 inhibition is not known. DPP4 also degrades the vasodilator brain natriuretic peptide (BNP) to a less potent metabolite. This study tested the hypothesis that DPP4 inhibition potentiates the vasodilator responses to GLP-1 and BNP in the human forearm.
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The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities.
Neuropsychologia (2014)
Wallace MT, Stevenson RA.
The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities.
Neuropsychologia.
2014 Nov;
64:105-23.
Abstract: Behavior, perception and cognition are strongly shaped by the synthesis of information across the different sensory modalities. Such multisensory integration often results in performance and perceptual benefits that reflect the additional information conferred by having cues from multiple senses providing redundant or complementary information. The spatial and temporal relationships of these cues provide powerful statistical information about how these cues should be integrated or "bound" in order to create a unified perceptual representation. Much recent work has examined the temporal factors that are integral in multisensory processing, with many focused on the construct of the multisensory temporal binding window - the epoch of time within which stimuli from different modalities is likely to be integrated and perceptually bound. Emerging evidence suggests that this temporal window is altered in a series of neurodevelopmental disorders, including autism, dyslexia and schizophrenia. In addition to their role in sensory processing, these deficits in multisensory temporal function may play an important role in the perceptual and cognitive weaknesses that characterize these clinical disorders. Within this context, focus on improving the acuity of multisensory temporal function may have important implications for the amelioration of the "higher-order" deficits that serve as the defining features of these disorders.
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Frequency and correlates of service access among youth with autism transitioning to adulthood.
Journal of autism and developmental disorders (2015)
Taylor JL, Henninger NA.
Frequency and correlates of service access among youth with autism transitioning to adulthood.
J Autism Dev Disord.
2015 Jan;
45(1):179-91.
Abstract: This study examined service receipt and unmet service needs among youth with autism spectrum disorders (ASD) in their last year of high school, as well as the youth (intellectual disability, race/ethnicity, autism severity, comorbid psychiatric diagnoses, behavior problems, adaptive behavior) and family (income, parental health, parental depressive symptoms, parental anxiety) correlates of service access. Thirty-nine families of youth with ASD participated. Data were collected via parental interview/questionnaire and youth psychological evaluation. Results suggested that this sample was underserved relative to a nationally-representative cohort. Those with a comorbid psychiatric diagnosis and lower levels of adaptive behavior received more services. Greater unmet needs were reported for youth who were racial/ethnic minorities, who had more behavior problems, and whose parents had greater anxiety.
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Racial differences in resistance to P2Y12 receptor antagonists in type 2 diabetic subjects.
The Journal of pharmacology and experimental therapeutics (2014)
Cleator JH, Duvernay MT, Holinstat M, Colowick NE, Hudson WJ, Song Y, Harrell FE, Hamm HE.
Racial differences in resistance to P2Y12 receptor antagonists in type 2 diabetic subjects.
J Pharmacol Exp Ther.
2014 Oct;
351(1):33-43.
Abstract: Although resistance to the P2Y12 antagonist clopidogrel is linked to altered drug metabolism, some studies suggest that these pharmacokinetic abnormalities only partially account for drug resistance. To circumvent pharmacokinetic complications and target P2Y12 receptor function we applied the direct P2Y12 antagonist 2-methylthio-AMP (2-methylthioadenosine 5'-monophosphate triethylammonium salt) to purified platelets ex vivo. Platelets were purified from healthy and type 2 diabetes mellitus (T2DM) patients and stimulated with thrombin or the selective protease-activated receptor agonists, protease-activated receptor 1-activating peptide (PAR1-AP), or PAR4-AP. Platelet activation as measured by αIIbβ3 activation, and P-selectin expression was monitored in 141 subjects. Our results demonstrate that, compared with healthy subjects, platelets from diabetic patients are resistant to inhibition by 2-methylthio-AMP, demonstrating P2Y12 pharmacodynamic defects among diabetic patients. Inhibition of thrombin-mediated αIIbβ3 activation by 2-methylthio-AMP was lower in diabetic platelets versus healthy platelets. Subgroup analysis revealed a racial difference in the resistance to 2-methylthio-AMP. We found no resistance in platelets from diabetic African Americans; they were inhibited by 2-methylthio-AMP equally as well as platelets from healthy African Americans. In contrast, platelets from Caucasian patients with diabetes were resistant to P2Y12 antagonism compared with healthy Caucasians. Multivariable analysis demonstrated that other variables, such as obesity, age, or gender, could not account for the differential resistance to 2-methylthio-AMP among races. These results suggest that in addition to altered drug metabolism, P2Y12 receptor function itself is altered in the Caucasian diabetic population. The racial difference in platelet function in T2DM is a novel finding, which may lead to differences in treatment as well as new targets for antiplatelet therapy.
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Hierarchical performance estimation in the statistical label fusion framework.
Medical image analysis (2014)
Asman AJ, Landman BA.
Hierarchical performance estimation in the statistical label fusion framework.
Med Image Anal.
2014 Oct;
18(7):1070-81.
Abstract: Label fusion is a critical step in many image segmentation frameworks (e.g., multi-atlas segmentation) as it provides a mechanism for generalizing a collection of labeled examples into a single estimate of the underlying segmentation. In the multi-label case, typical label fusion algorithms treat all labels equally - fully neglecting the known, yet complex, anatomical relationships exhibited in the data. To address this problem, we propose a generalized statistical fusion framework using hierarchical models of rater performance. Building on the seminal work in statistical fusion, we reformulate the traditional rater performance model from a multi-tiered hierarchical perspective. The proposed approach provides a natural framework for leveraging known anatomical relationships and accurately modeling the types of errors that raters (or atlases) make within a hierarchically consistent formulation. Herein, the primary contributions of this manuscript are: (1) we provide a theoretical advancement to the statistical fusion framework that enables the simultaneous estimation of multiple (hierarchical) confusion matrices for each rater, (2) we highlight the amenability of the proposed hierarchical formulation to many of the state-of-the-art advancements to the statistical fusion framework, and (3) we demonstrate statistically significant improvement on both simulated and empirical data. Specifically, both theoretically and empirically, we show that the proposed hierarchical performance model provides substantial and significant accuracy benefits when applied to two disparate multi-atlas segmentation tasks: (1) 133 label whole-brain anatomy on structural MR, and (2) orbital anatomy on CT.
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Insulin resistance is not associated with thermogenic effect of a high-fat meal in obese children.
Nutrition research (New York, N.Y.) (2014)
Chan J, Lomenick JP, Buchowski MS, Shoemaker AH.
Insulin resistance is not associated with thermogenic effect of a high-fat meal in obese children.
Nutr Res.
2014 Jun;
34(6):486-90.
Abstract: In adults, insulin resistance may decrease the thermogenic effect of food, contributing to weight gain. We aimed to determine the effect of insulin resistance on energy expenditure in children with long-standing obesity. We hypothesized that thermogenic effect of food would decrease with increasing insulin resistance. Energy expenditure was measured using whole room indirect calorimetry in obese children 7 to 18 years old. Participants were fed a high-fat meal with energy content equal to 35% of measured resting energy expenditure. Thermogenic effect of food was measured for 180 minutes posttest meal and expressed as a percent of calories consumed. Body composition was assessed using whole-body dual-energy x-ray absorptiometry. Fasting glucose, insulin, and hemoglobin A1C were measured. Complete data were available for 25 children (median age, 12.1 years; 52% male). As expected, a significant decrease in resting energy expenditure was observed with increasing Tanner stage (P = .02 by Kruskal-Wallis test). Insulin sensitivity, as determined by homeostasis model assessment index equation, did not significantly affect resting energy expenditure (P = .3) or thermogenic effect of food (P = .7) after adjustment for Tanner stage. In conclusion, our study did not find an association between insulin resistance and energy expenditure in obese children.
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Evidence for diminished multisensory integration in autism spectrum disorders.
Journal of autism and developmental disorders (2014)
Stevenson RA, Siemann JK, Woynaroski TG, Schneider BC, Eberly HE, Camarata SM, Wallace MT.
Evidence for diminished multisensory integration in autism spectrum disorders.
J Autism Dev Disord.
2014 Dec;
44(12):3161-7.
Abstract: Individuals with autism spectrum disorders (ASD) exhibit alterations in sensory processing, including changes in the integration of information across the different sensory modalities. In the current study, we used the sound-induced flash illusion to assess multisensory integration in children with ASD and typically-developing (TD) controls. Thirty-one children with ASD and 31 age and IQ matched TD children (average age = 12 years) were presented with simple visual (i.e., flash) and auditory (i.e., beep) stimuli of varying number. In illusory conditions, a single flash was presented with 2-4 beeps. In TD children, these conditions generally result in the perception of multiple flashes, implying a perceptual fusion across vision and audition. In the present study, children with ASD were significantly less likely to perceive the illusion relative to TD controls, suggesting that multisensory integration and cross-modal binding may be weaker in some children with ASD. These results are discussed in the context of previous findings for multisensory integration in ASD and future directions for research.
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Autonomic blockade improves insulin sensitivity in obese subjects.
Hypertension (Dallas, Tex. : 1979) (2014)
Gamboa A, Okamoto LE, Arnold AC, Figueroa RA, Diedrich A, Raj SR, Paranjape SY, Farley G, Abumrad N, Biaggioni I.
Autonomic blockade improves insulin sensitivity in obese subjects.
Hypertension.
2014 Oct;
64(4):867-74.
Abstract: Obesity is an important risk factor for the development of insulin resistance. Initial compensatory mechanisms include an increase in insulin levels, which are thought to induce sympathetic activation in an attempt to restore energy balance. We have previously shown, however, that sympathetic activity has no beneficial effect on resting energy expenditure in obesity. On the contrary, we hypothesize that sympathetic activation contributes to insulin resistance. To test this hypothesis, we determined insulin sensitivity using a standard hyperinsulinemic euglycemic clamp protocol in obese subjects randomly assigned in a crossover design 1 month apart to receive saline (intact day) or trimetaphan (4 mg/min IV, autonomic blocked day). Whole-body glucose uptake (MBW in mg/kg per minute) was used as index of maximal muscle glucose use. During autonomic blockade, we clamped blood pressure with a concomitant titrated intravenous infusion of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. Of the 21 obese subjects (43±2 years; 35±2 kg/m(2) body mass index) studied, 14 were insulin resistant; they were more obese, had higher plasma glucose and insulin, and had higher muscle sympathetic nerve activity (23.3±1.5 versus 17.2±2.1 burst/min; P=0.03) when compared with insulin-sensitive subjects. Glucose use improved during autonomic blockade in insulin-resistant subjects (MBW 3.8±0.3 blocked versus 3.1±0.3 mg/kg per minute intact; P=0.025), with no effect in the insulin-sensitive group. These findings support the concept that sympathetic activation contributes to insulin resistance in obesity and may result in a feedback loop whereby the compensatory increase in insulin levels contributes to greater sympathetic activation.
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Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.
Antimicrobial agents and chemotherapy (2014)
Dooley KE, Luetkemeyer AF, Park JG, Allen R, Cramer Y, Murray S, Sutherland D, Aweeka F, Koletar SL, Marzan F, Bao J, Savic R, Haas DW, AIDS Clinical Trials Group A5306 Study Team.
Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.
Antimicrob Agents Chemother.
2014 Sep;
58(9):5245-52.
Abstract: There is an urgent need for new antituberculosis (anti-TB) drugs, including agents that are safe and effective with concomitant antiretrovirals (ARV) and first-line TB drugs. PA-824 is a novel antituberculosis nitroimidazole in late-phase clinical development. Cytochrome P450 (CYP) 3A, which can be induced or inhibited by ARV and antituberculosis drugs, is a minor (∼20%) metabolic pathway for PA-824. In a phase I clinical trial, we characterized interactions between PA-824 and efavirenz (arm 1), lopinavir/ritonavir (arm 2), and rifampin (arm 3) in healthy, HIV-uninfected volunteers without TB disease. Participants in arms 1 and 2 were randomized to receive drugs via sequence 1 (PA-824 alone, washout, ARV, and ARV plus PA-824) or sequence 2 (ARV, ARV with PA-824, washout, and PA-824 alone). In arm 3, participants received PA-824 and then rifampin and then both. Pharmacokinetic sampling occurred at the end of each dosing period. Fifty-two individuals participated. Compared to PA-824 alone, plasma PA-824 values (based on geometric mean ratios) for maximum concentration (Cmax), area under the concentration-time curve from 0 to 24 h (AUC0-24), and trough concentration (Cmin) were reduced 28%, 35%, and 46% with efavirenz, 13%, 17%, and 21% with lopinavir-ritonavir (lopinavir/r) and 53%, 66%, and 85% with rifampin, respectively. Medications were well tolerated. In conclusion, lopinavir/r had minimal effect on PA-824 exposures, supporting PA-824 use with lopinavir/r without dose adjustment. PA-824 exposures, though, were reduced more than expected when given with efavirenz or rifampin. The clinical implications of these reductions will depend upon data from current clinical trials defining PA-824 concentration-effect relationships. (This study has been registered at ClinicalTrials.gov under registration no. NCT01571414.).
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The impact of multisensory integration deficits on speech perception in children with autism spectrum disorders.
Frontiers in psychology (2014)
Stevenson RA, Segers M, Ferber S, Barense MD, Wallace MT.
The impact of multisensory integration deficits on speech perception in children with autism spectrum disorders.
Front Psychol.
2014;
5:379.
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The interaction between stimulus factors and cognitive factors during multisensory integration of audiovisual speech.
Frontiers in psychology (2014)
Stevenson RA, Wallace MT, Altieri N.
The interaction between stimulus factors and cognitive factors during multisensory integration of audiovisual speech.
Front Psychol.
2014;
5:352.
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Reversing vascular dysfunction in rheumatoid arthritis: improved augmentation index but not endothelial function with peroxisome proliferator-activated receptor γ agonist therapy.
Arthritis & rheumatology (Hoboken, N.J.) (2014)
Ormseth MJ, Oeser AM, Cunningham A, Bian A, Shintani A, Solus J, Tanner SB, Stein CM.
Reversing vascular dysfunction in rheumatoid arthritis: improved augmentation index but not endothelial function with peroxisome proliferator-activated receptor γ agonist therapy.
Arthritis Rheumatol.
2014 Sep;
66(9):2331-8.
Abstract: To examine the hypothesis that improving insulin sensitivity improves vascular function in rheumatoid arthritis (RA).
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Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development.
Journal of neurodevelopmental disorders (2014)
Koran ME, Hohman TJ, Edwards CM, Vega JN, Pryweller JR, Slosky LE, Crockett G, Villa de Rey L, Meda SA, Dankner N, Avery SN, Blackford JU, Dykens EM, Thornton-Wells TA.
Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development.
J Neurodev Disord.
2014;
6(1):8.
Abstract: Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS.
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Adolescence, Stress and Cortisol in Autism Spectrum Disorders.
OA autism (2014)
Corbett BA, Simon D.
Adolescence, Stress and Cortisol in Autism Spectrum Disorders.
OA Autism.
2014 Feb 1;
1(1):2.
Abstract: Adolescence, the transition between childhood and adulthood, is a period of remarkable physiological, psychological and social change. A variety of physiological changes coincide with the dynamic transition, which is evident in the regulation and responsivity of the Limbic-Hypothalamic-Pituitary-Adrenocortical (LHPA) axis. Specifically, elevations in diurnal basal cortisol levels have been reported, as well as higher cortisol in response to perceived stressors. While this enhanced responsivity may help prepare the individual to adapt to increased demands and new challenges, it may also mark a time of increased vulnerability in populations already prone to enhanced physiological arousal and poor adaption to change, such as autism. To date most studies investigating the integrity of the LHPA axis in children with autism spectrum disorders (ASD) have shown more variable diurnal regulation and a pattern of enhanced responsivity to stress. There is also evidence of more marked reactivity over development suggesting that adolescence may be a time of increased risk for enhanced physiological arousal and social stress. The following review briefly summarizes the literature to date on autism, adolescence and salivary cortisol. The current summary suggests that enhanced study of the interplay between social functioning and stress during the adolescent period in ASD is warranted.
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Self-assessed performance improves statistical fusion of image labels.
Medical physics (2014)
Bryan FW, Xu Z, Asman AJ, Allen WM, Reich DS, Landman BA.
Self-assessed performance improves statistical fusion of image labels.
Med Phys.
2014 Mar;
41(3):031903.
Abstract: Expert manual labeling is the gold standard for image segmentation, but this process is difficult, time-consuming, and prone to inter-individual differences. While fully automated methods have successfully targeted many anatomies, automated methods have not yet been developed for numerous essential structures (e.g., the internal structure of the spinal cord as seen on magnetic resonance imaging). Collaborative labeling is a new paradigm that offers a robust alternative that may realize both the throughput of automation and the guidance of experts. Yet, distributing manual labeling expertise across individuals and sites introduces potential human factors concerns (e.g., training, software usability) and statistical considerations (e.g., fusion of information, assessment of confidence, bias) that must be further explored. During the labeling process, it is simple to ask raters to self-assess the confidence of their labels, but this is rarely done and has not been previously quantitatively studied. Herein, the authors explore the utility of self-assessment in relation to automated assessment of rater performance in the context of statistical fusion.
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Groupwise multi-atlas segmentation of the spinal cord's internal structure.
Medical image analysis (2014)
Asman AJ, Bryan FW, Smith SA, Reich DS, Landman BA.
Groupwise multi-atlas segmentation of the spinal cord's internal structure.
Med Image Anal.
2014 Apr;
18(3):460-71.
Abstract: The spinal cord is an essential and vulnerable component of the central nervous system. Differentiating and localizing the spinal cord internal structure (i.e., gray matter vs. white matter) is critical for assessment of therapeutic impacts and determining prognosis of relevant conditions. Fortunately, new magnetic resonance imaging (MRI) sequences enable clinical study of the in vivo spinal cord's internal structure. Yet, low contrast-to-noise ratio, artifacts, and imaging distortions have limited the applicability of tissue segmentation techniques pioneered elsewhere in the central nervous system. Additionally, due to the inter-subject variability exhibited on cervical MRI, typical deformable volumetric registrations perform poorly, limiting the applicability of a typical multi-atlas segmentation framework. Thus, to date, no automated algorithms have been presented for the spinal cord's internal structure. Herein, we present a novel slice-based groupwise registration framework for robustly segmenting cervical spinal cord MRI. Specifically, we provide a method for (1) pre-aligning the slice-based atlases into a groupwise-consistent space, (2) constructing a model of spinal cord variability, (3) projecting the target slice into the low-dimensional space using a model-specific registration cost function, and (4) estimating robust segmentation susing geodesically appropriate atlas information. Moreover, the proposed framework provides a natural mechanism for performing atlas selection and initializing the free model parameters in an informed manner. In a cross-validation experiment using 67 MR volumes of the cervical spinal cord, we demonstrate sub-millimetric accuracy, significant quantitative and qualitative improvement over comparable multi-atlas frameworks, and provide insight into the sensitivity of the associated model parameters.
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Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition.
Hypertension (Dallas, Tex. : 1979) (2014)
Devin JK, Pretorius M, Nian H, Yu C, Billings FT 4th, Brown NJ.
Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition.
Hypertension.
2014 May;
63(5):951-7.
Abstract: Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce postprandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme (ACE). During ACE inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, whereas bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when ACE is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg by mouth or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat; however, substance P increased heart rate and vascular release of norepinephrine during combined ACE and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined ACE and dipeptidyl peptidase-4 inhibition.
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HPV vaccine use among African American girls: qualitative formative research using a participatory social marketing approach.
Gynecologic oncology (2014)
Hull PC, Williams EA, Khabele D, Dean C, Bond B, Sanderson M.
HPV vaccine use among African American girls: qualitative formative research using a participatory social marketing approach.
Gynecol Oncol.
2014 Mar;
132 Suppl :S13-20.
Abstract: To generate recommendations for framing messages to promote HPV vaccination, specifically for African American adolescents and their parents who have not yet made a decision about the vaccine (the "Undecided" market segment).
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COLLABORATIVE LABELING OF MALIGNANT GLIOMA.