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Contested Illness Legitimation: Challenges, strategies, and knowledges among women of color and low-income women seeking disability benefits

Northwestern University
  • "Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain.
    Social science & medicine (1982) (2017)
    Pryma J. "Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain. Soc Sci Med. 2017 Mar 24; 181:66-73.
    Abstract: Recent research examines how women claim chronic pain in response to gendered moral discourses. However, extant research does not explore how race shapes the moral boundary-work performed by women suffering from disabling chronic pain. Through the qualitative analysis of twenty-four semi-structured interviews with women fibromyalgia sufferers conducted between October 2014 and August 2016 in the U.S.A., I demonstrate how women with fibromyalgia claim chronic pain by doing moral boundary-work, referencing gendered and racialized moral discourses that structure how claims of chronic pain as disability are and are not read as legitimate by doctors, disability bureaucrats and personal networks. Extending Hansen et al.'s work on stigma and the "pathologization of poverty," I suggest that, per my sample, the different moral discourses deployed in white and Black women's claims of chronic pain can be explained by the racialized and gendered boundaries of citizenship that structure U.S. welfare and disability politics. Finally, I argue for intersectionality's relevance to research on moral boundary-work and the medicalization of poverty.
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Psychiatric Genotype/Phenotype Repository

Vanderbilt University Medical Center
  • Personality traits predicting quality of life and overall functioning in schizophrenia.
    Schizophrenia research (2016)
    Ridgewell C, Blackford JU, McHugo M, Heckers S. Personality traits predicting quality of life and overall functioning in schizophrenia. Schizophr Res. 2016 Oct 13; :.
    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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Bridging sensory function to core ASD symptoms

Vanderbilt University Medical Center
  • The associations between multisensory temporal processing and symptoms of schizophrenia.
    Schizophrenia research (2016)
    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. 2016 Oct 13; :.
    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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  • 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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  • 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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  • 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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  • 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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  • 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 May 21; 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 May 1; 5:352.
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  • Multisensory temporal integration in autism spectrum disorders.
    The Journal of neuroscience : the official journal of the Society for Neuroscience (2014)
    Stevenson RA, Siemann JK, Schneider BC, Eberly HE, Woynaroski TG, Camarata SM, Wallace MT. Multisensory temporal integration in autism spectrum disorders. J Neurosci. 2014 Jan 15; 34(3):691-7.
    Abstract: The new DSM-5 diagnostic criteria for autism spectrum disorders (ASDs) include sensory disturbances in addition to the well-established language, communication, and social deficits. One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept. This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs, an important cue for multisensory integration. Such impairments in multisensory processing may cascade into higher-level deficits, impairing day-to-day functioning on tasks, such as speech perception. To investigate multisensory temporal processing deficits in ASD and their links to speech processing, the current study mapped performance on a number of multisensory temporal tasks (with both simple and complex stimuli) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals. High-functioning children with ASD were compared with a group of typically developing children. Performance on the multisensory temporal tasks varied with stimulus complexity for both groups; less precise temporal processing was observed with increasing stimulus complexity. Notably, individuals with ASD showed a speech-specific deficit in multisensory temporal processing. Most importantly, the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities. Collectively, the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD, strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains, such as language and communication.
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  • Brief report: Arrested development of audiovisual speech perception 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. Brief report: Arrested development of audiovisual speech perception in autism spectrum disorders. J Autism Dev Disord. 2014 Jun; 44(6):1470-7.
    Abstract: Atypical communicative abilities are a core marker of Autism Spectrum Disorders (ASD). A number of studies have shown that, in addition to auditory comprehension differences, individuals with autism frequently show atypical responses to audiovisual speech, suggesting a multisensory contribution to these communicative differences from their typically developing peers. To shed light on possible differences in the maturation of audiovisual speech integration, we tested younger (ages 6-12) and older (ages 13-18) children with and without ASD on a task indexing such multisensory integration. To do this, we used the McGurk effect, in which the pairing of incongruent auditory and visual speech tokens typically results in the perception of a fused percept distinct from the auditory and visual signals, indicative of active integration of the two channels conveying speech information. Whereas little difference was seen in audiovisual speech processing (i.e., reports of McGurk fusion) between the younger ASD and TD groups, there was a significant difference at the older ages. While TD controls exhibited an increased rate of fusion (i.e., integration) with age, children with ASD failed to show this increase. These data suggest arrested development of audiovisual speech integration in ASD. The results are discussed in light of the extant literature and necessary next steps in research.
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Genes and alterations in brain structure and function in depression

Vanderbilt University Medical Center
  • Effects of early life stress on depression, cognitive performance and brain morphology.
    Psychological medicine (2016)
    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. 2016 Sep 29; :1-11.
    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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  • 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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Nashville Early Diagnosis Lung Cancer Trial

Vanderbilt University Medical Center
  • Radiological Image traits Predictive of Cancer Status in Pulmonary Nodules.
    Clinical cancer research : an official journal of the American Association for Cancer Research (2016)
    Liu Y, Balagurunathan Y, Atwater T, Antic S, Li Q, Walker RC, Smith G, Massion PP, Schabath MB, Gillies RJ. Radiological Image traits Predictive of Cancer Status in Pulmonary Nodules. Clin Cancer Res. 2016 Sep 23; :.
    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.
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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 (FEV1) in COPD, but that the ratio of SIgA/MUC5B is a better predictor of FEV1, 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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  • 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 Sep 17; 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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Social and Behavioral Determinants of Health Survey: A Pilot Study

Vanderbilt University Medical Center
  • Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study.
    American journal of preventive medicine (2016)
    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. 2016 Sep 19; :.
    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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Validation of the BRFSS Sleep Questions

University of Rochester
  • Revisions to the BRFSS Sleep Questions.
    Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine (2016)
    Jungquist CR, Klingman KJ, Dickerson SS. Revisions to the BRFSS Sleep Questions. J Clin Sleep Med. 2016 Sep 13; :.
    Abstract: To revise and enhance the current Behavioral Risk Factor Surveillance System (BRFSS) sleep questions for detection of sleep/wake disorders that contribute to health burden.
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  • Validation of Capturing Sleep Diary Data via a Wrist-Worn Device.
    Sleep disorders (2015)
    Jungquist CR, Pender JJ, Klingman KJ, Mund J. Validation of Capturing Sleep Diary Data via a Wrist-Worn Device. Sleep Disord. 2015; 2015:758937.
    Abstract: Paper sleep diaries are the gold standard for assessment of sleep continuity variables in clinical practice as well as research. Unfortunately, paper diaries can be filled out weekly instead of daily, lost, illegible or destroyed; and are considered out of date according to the newer technology savvy generations. In this study, we assessed the reliability and validity of using a wrist-worn electronic sleep diary. Design. A prospective design was used to compare capturing 14 days of sleep continuity data via paper to a wrist-worn electronic device that also captured actigraphy data. Results. Thirty-five healthy community dwelling adults with mean (sd) age of 36 (15), 80% Caucasians, and 74% females were enrolled. All sleep continuity variables via electronic and paper diary capture methods were significantly correlated with moderate, positive relationships. Assessment of validity revealed that electronic data capture had a significant relationship with objective measure of sleep continuity variables as measured by actigraphy. Paper diary variables were not significantly associated with objective measures. Conclusions. The use of a wrist-worn device to capture daily sleep diary data is as accurate as and for some variables more accurate than using paper diaries.
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  • Validation of the Behavioral Risk Factor Surveillance System Sleep Questions.
    Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine (2016)
    Jungquist CR, Mund J, Aquilina AT, Klingman K, Pender J, Ochs-Balcom H, van Wijngaarden E, Dickerson SS. Validation of the Behavioral Risk Factor Surveillance System Sleep Questions. J Clin Sleep Med. 2016 Mar; 12(3):301-10.
    Abstract: leep problems may constitute a risk for health problems, including cardiovascular disease, depression, diabetes, poor work performance, and motor vehicle accidents. The primary purpose of this study was to assess the validity of the current Behavioral Risk Factor Surveillance System (BRFSS) sleep questions by establishing the sensitivity and specificity for detection of sleep/ wake disturbance.
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FAST: Fibromyalgia Activity Study with TENS

Vanderbilt University Medical Center
  • Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia.
    Pain medicine (Malden, Mass.) (2016)
    Merriwether EN, Rakel BA, Zimmerman MB, Dailey DL, Vance CG, 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. 2016 Aug 24; :.
    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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  • 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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  • 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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  • 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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Focus Groups to Assess Patient Perspectives on the PREDICT Program

Vanderbilt University Medical Center
  • Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.
    Genetics in medicine : official journal of the American College of Medical Genetics (2016)
    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. 2016 Aug 25; :.
    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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  • Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project.
    Clinical pharmacology and therapeutics (2012)
    Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH, Delaney JT, Bowton E, Brothers K, Johnson K, Crawford DC, Schildcrout J, Masys DR, Dilks HH, Wilke RA, Clayton EW, Shultz E, Laposata M, McPherson J, Jirjis JN, Roden DM. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012 Jul; 92(1):87-95.
    Abstract: The promise of "personalized medicine" guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision-support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health-care provider, identification of relevant genetic variations for implementation, assay reliability, point-of-care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point-of-care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.
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Treatment of Overweight Induced by Antipsychotic Medication in Young People with ASD

Vanderbilt University Medical Center
  • 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 Nervous System and Nitric Oxide and tPA Interactions" (NHLBI – P50-HL81009 (Oates/Vaughan/Muldowney))

Vanderbilt University Medical Center
  • 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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The Autonomic Nervous System and Metabolic Syndrome

Vanderbilt University Medical Center
  • 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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  • 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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  • Sympathetic activation and nitric oxide function in early hypertension.
    American journal of physiology. Heart and circulatory physiology (2012)
    Gamboa A, Okamoto LE, Diedrich A, Choi L, Robertson D, Farley G, Paranjape S, Biaggioni I. Sympathetic activation and nitric oxide function in early hypertension. Am J Physiol Heart Circ Physiol. 2012 Apr 1; 302(7):H1438-43.
    Abstract: The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with N(ω)-monomethyl-l-arginine (L-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to L-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as "positive" controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, L-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study.
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  • Interventional approaches to reduce sympathetic activity in resistant hypertension: to ablate or stimulate?
    Hypertension (Dallas, Tex. : 1979) (2012)
    Biaggioni I. Interventional approaches to reduce sympathetic activity in resistant hypertension: to ablate or stimulate? Hypertension. 2012 Feb; 59(2):194-5.
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An Observational Cohort Study of Adipose Tissue and Immune Activation in Treated HIV Infection

Vanderbilt University Medical Center
  • Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV.
    AIDS research and human retroviruses (2016)
    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. 2016 Sep 14; :.
    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 (CD45RO(-)CCR7(+)CD27(+)), activated (CD38(+) and CD38(+)DR(+)), 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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  • 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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  • 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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Risk and Resiliency for Youth with Autism during the Transition to Adulthood

Vanderbilt University Medical Center
  • 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 Jul 27; 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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  • 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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THE HEAD INJURY-ASSOCIATED PHOTOSENSITIVITY AND PUPILLARY FUNCTION (HIPP) STUDY

The Ohio State University
  • Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI.
    Optometry and vision science : official publication of the American Academy of Optometry (2017)
    Yuhas PT, Shorter PD, McDaniel CE, Earley MJ, Hartwick AT. Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI. Optom Vis Sci. 2017 Jan; 94(1):108-117.
    Abstract: Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light.
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Afferent hyperactivity mechanisms in overactive bladder syndrome

Vanderbilt University Medical Center
  • Temporal summation to thermal stimuli is elevated in women with overactive bladder syndrome.
    Neurourology and urodynamics (2016)
    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. 2016 Jul 19; :.
    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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Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease—Aim 1

Vanderbilt University Medical Center
  • 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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Masculinity and men's health: a psychometric calibration survey

Vanderbilt University Medical Center
  • 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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  • 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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Using Tailoring and Technology to Promote Health Equity in African American Men

Vanderbilt University Medical Center
  • 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.
    Show details  Open in PubMed
  • 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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  • 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 Mar 1; :.
    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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The Family Dynamics Survey

University of Rochester
  • Reciprocal influences among family processes and toddlers' sleep problems.
    Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) (2016)
    Peltz JS, Rogge RD, Sturge-Apple ML, O'Connor TG, Pigeon WR. Reciprocal influences among family processes and toddlers' sleep problems. J Fam Psychol. 2016 Sep; 30(6):720-31.
    Abstract: The current study examined bidirectional relations between children's sleep problems and parents' relationship satisfaction, coparental cooperation, and global family functioning in a sample of 249 families with 2-3-year-old children. Mothers and fathers were assessed across 5 waves with 2-month lags; the target children (53% female) were 2.8 years old (SD = .62) at baseline. Results of lagged path analyses indicated that children's sleep problems were reciprocally related to lower relationship satisfaction for mothers after accounting for covariates; however, for fathers, only relationship satisfaction predicted residual decreases in children's sleep problems 2 months later. Coparental cooperation also demonstrated reciprocal predictive links with fewer children's sleep problems in mothers; no such effect was found for fathers. Finally, for fathers, family functioning predicted residual decreases in children's sleep problems 2 months later across the 5 waves of the study. Findings build on a growing body of literature addressing reciprocal links between toddlers' sleep problems and adaptive family processes and highlight the importance of examining children's sleep within the context of the larger family system. (PsycINFO Database Record
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The Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

Vanderbilt University Medical Center
  • 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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Brain Activation and Pain Reports in People with Alzheimer's Disease

Vanderbilt University Medical Center
  • 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 in Chronic Kidney Disease

Vanderbilt University Medical Center
  • 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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  • 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 Feb 23; 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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  • 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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  • 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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Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

Case Western Reserve University
  • The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample.
    BMC psychiatry (2016)
    Oedegaard KJ, Alda M, Anand A, Andreassen OA, Balaraman Y, Berrettini WH, Bhattacharjee A, Brennand KJ, Burdick KE, Calabrese JR, Calkin CV, Claasen A, Coryell WH, Craig D, DeModena A, Frye M, Gage FH, Gao K, Garnham J, Gershon E, Jakobsen P, Leckband SG,. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry. 2016 May 5; 16:129.
    Abstract: Bipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response.
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Effect of Sildenafil Citrate on Insulin and Endothelia Function in Obese African American Women

Vanderbilt University Medical Center
  • 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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  • 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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  • 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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  • 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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Effects of Exenatide on Body Weight in Patients with Hypothalamic Obesity

Vanderbilt University Medical Center
  • 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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Collaborative Online Labeling of Medical Images

Vanderbilt University Medical Center
  • Improving Cerebellar Segmentation with Statistical Fusion.
    Proceedings of SPIE--the International Society for Optical Engineering (2016)
    Plassard AJ, Yang Z, 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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  • 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 a posteriori 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(2) 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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  • 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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  • 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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  • COLLABORATIVE LABELING OF MALIGNANT GLIOMA.
    Proceedings. IEEE International Symposium on Biomedical Imaging (2012)
    Xu Z, Asman AJ, Singh E, Chambless L, Thompson R, Landman BA. COLLABORATIVE LABELING OF MALIGNANT GLIOMA. Proc IEEE Int Symp Biomed Imaging. 2012 Dec 31; 2012:1148-1151.
    Abstract: Malignant gliomas represent an aggressive class of central nervous system neoplasms which are often treated by maximal surgical resection. Herein, we seek to improve the methods available to quantify the extent of tumors as seen on magnetic resonance imaging using Internet-based, collaborative labeling. In a study of clinically acquired images, we demonstrate that teams of minimally trained human raters are able to reliably characterize the gadolinium-enhancing core and edema tumor regions (Dice ≈ 0.9). The collaborative approach is highly parallel and efficient in terms of time (the total time spent by the collective is equivalent to that of a single expert) and resources (only minimal training and no hardware is provided to the participants). Hence, collaborative labeling is a very promising new technique with potentially wide applicability to facilitate cost-effective manual labeling of medical imaging data.
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  • Out-of-atlas likelihood estimation using multi-atlas segmentation.
    Medical physics (2013)
    Asman AJ, Chambless LB, Thompson RC, Landman BA. Out-of-atlas likelihood estimation using multi-atlas segmentation. Med Phys. 2013 Apr; 40(4):043702.
    Abstract: Multi-atlas segmentation has been shown to be highly robust and accurate across an extraordinary range of potential applications. However, it is limited to the segmentation of structures that are anatomically consistent across a large population of potential target subjects (i.e., multi-atlas segmentation is limited to "in-atlas" applications). Herein, the authors propose a technique to determine the likelihood that a multi-atlas segmentation estimate is representative of the problem at hand, and, therefore, identify anomalous regions that are not well represented within the atlases.
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  • Collaborative Labeling of Malignant Glioma with WebMILL: A First Look.
    Proceedings of SPIE--the International Society for Optical Engineering (2012)
    Singh E, Asman AJ, Xu Z, Chambless L, Thompson R, Landman BA. Collaborative Labeling of Malignant Glioma with WebMILL: A First Look. Proc SPIE Int Soc Opt Eng. 2012 Apr 5; 8318:.
    Abstract: Malignant gliomas are the most common form of primary neoplasm in the central nervous system, and one of the most rapidly fatal of all human malignancies. They are treated by maximal surgical resection followed by radiation and chemotherapy. Herein, we seek to improve the methods available to quantify the extent of tumors using newly presented, collaborative labeling techniques on magnetic resonance imaging. Traditionally, labeling medical images has entailed that expert raters operate on one image at a time, which is resource intensive and not practical for very large datasets. Using many, minimally trained raters to label images has the possibility of minimizing laboratory requirements and allowing high degrees of parallelism. A successful effort also has the possibility of reducing overall cost. This potentially transformative technology presents a new set of problems, because one must pose the labeling challenge in a manner accessible to people with little or no background in labeling medical images and raters cannot be expected to read detailed instructions. Hence, a different training method has to be employed. The training must appeal to all types of learners and have the same concepts presented in multiple ways to ensure that all the subjects understand the basics of labeling. Our overall objective is to demonstrate the feasibility of studying malignant glioma morphometry through statistical analysis of the collaborative efforts of many, minimally-trained raters. This study presents preliminary results on optimization of the WebMILL framework for neoplasm labeling and investigates the initial contributions of 78 raters labeling 98 whole-brain datasets.
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  • Towards Automatic Quantitative Quality Control for MRI.
    Proceedings of SPIE--the International Society for Optical Engineering (2012)
    Lauzon CB, Caffo BC, Landman BA. Towards Automatic Quantitative Quality Control for MRI. Proc SPIE Int Soc Opt Eng. 2012 Feb 23; 8314:.
    Abstract: Quality and consistency of clinical and research data collected from Magnetic Resonance Imaging (MRI) scanners may become suspect due to a wide variety of common factors including, experimental changes, hardware degradation, hardware replacement, software updates, personnel changes, and observed imaging artifacts. Standard practice limits quality analysis to visual assessment by a researcher/clinician or a quantitative quality control based upon phantoms which may not be timely, cannot account for differing experimental protocol (e.g. gradient timings and strengths), and may not be pertinent to the data or experimental question at hand. This paper presents a parallel processing pipeline developed towards experiment specific automatic quantitative quality control of MRI data using diffusion tensor imaging (DTI) as an experimental test case. The pipeline consists of automatic identification of DTI scans run on the MRI scanner, calculation of DTI contrasts from the data, implementation of modern statistical methods (wild bootstrap and SIMEX) to assess variance and bias in DTI contrasts, and quality assessment via power calculations and normative values. For this pipeline, a DTI specific power calculation analysis is developed as well as the first incorporation of bias estimates in DTI data to improve statistical analysis.
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  • Generalized Statistical Label Fusion using Multiple Consensus Levels.
    Proceedings of SPIE--the International Society for Optical Engineering (2012)
    Xu Z, Asman AJ, Landman BA. Generalized Statistical Label Fusion using Multiple Consensus Levels. Proc SPIE Int Soc Opt Eng. 2012 Feb 23; 8314:.
    Abstract: Segmentation plays a critical role in exposing connections between biological structure and function. The process of label fusion collects and combines multiple observations into a single estimate. Statistically driven techniques provide mechanisms to optimally combine segmentations; yet, optimality hinges upon accurate modeling of rater behavior. Traditional approaches, e.g., Majority Vote and Simultaneous Truth and Performance Level Estimation (STAPLE), have been shown to yield excellent performance in some cases, but do not account for spatial dependences of rater performance (i.e., regional task difficulty). Recently, the COnsensus Level, Labeler Accuracy and Truth Estimation (COLLATE) label fusion technique augmented the seminal STAPLE approach to simultaneously estimate regions of relative consensus versus confusion along with rater performance. Herein, we extend the COLLATE framework to account for multiple consensus levels. Toward this end, we posit a generalized model of rater behavior of which Majority Vote, STAPLE, STAPLE Ignoring Consensus Voxels, and COLLATE are special cases. The new algorithm is evaluated with simulations and shown to yield improved performance in cases with complex region difficulties. Multi-COLLATE achieve these results by capturing different consensus levels. The potential impacts and applications of generative model to label fusion problems are discussed.
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  • Robust statistical fusion of image labels.
    IEEE transactions on medical imaging (2012)
    Landman BA, Asman AJ, Scoggins AG, Bogovic JA, Xing F, Prince JL. Robust statistical fusion of image labels. IEEE Trans Med Imaging. 2012 Feb; 31(2):512-22.
    Abstract: Image labeling and parcellation (i.e., assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability.
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Phase 4 Randomized double-blind, active and placebo-controlled multicenter study evaluating the neuropsychiatric safety and efficacy of 12 weeks varenicline tartrate 1 mg bid and bupropion hydrochloride 150 mg bid for smoking cessation in subjects with and without a history of psychiatric disorders

University of Minnesota
  • Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial.
    Lancet (London, England) (2016)
    Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, Ascher J, Russ C, Krishen A, Evins AE. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016 Jun 18; 387(10037):2507-20.
    Abstract: Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion. Their efficacy relative to nicotine patch largely relies on indirect comparisons, and there is limited information on safety and efficacy in smokers with psychiatric disorders. We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders.
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Perceptual Organization of Speech by Adults with Cochlear Implants

The Ohio State University
  • Word Recognition Variability With Cochlear Implants: The Degradation of Phonemic Sensitivity.
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (2016)
    Moberly AC, Lowenstein JH, Nittrouer S. Word Recognition Variability With Cochlear Implants: The Degradation of Phonemic Sensitivity. Otol Neurotol. 2016 Jun; 37(5):470-7.
    Abstract: Cochlear implants (CIs) do not automatically restore speech recognition for postlingually deafened adults. Average word recognition remains at 60%, and enormous variability exists. Understanding speech requires knowledge of phonemic codes, the basic sound units of language. Hearing loss may result in degeneration of these long-term mental representations (i.e., "phonemic sensitivity"), and CI use may not adequately restore those representations. This investigation examined whether phonemic sensitivity is degraded for CI users, and whether this degradation results in poorer word recognition.
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Memory

Vanderbilt University Medical Center
  • The Vanderbilt Memory &amp;amp; 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 &amp;amp; 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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Vitamin D supplementation and HIV related complications in children and young adults

University Hospitals Cleveland Medical Center
  • Vitamin D and bone loss in HIV.
    Current opinion in HIV and AIDS (2016)
    Hileman CO, Overton ET, McComsey GA. Vitamin D and bone loss in HIV. Curr Opin HIV AIDS. 2016 May; 11(3):277-84.
    Abstract: Bone health has become an increasingly important aspect of the care of HIV-infected patients as bone loss with antiretroviral therapy (ART) initiation is significant and osteopenia and osteoporosis are highly prevalent. Vitamin D is tightly linked to calcium balance and bone health, and vitamin D deficiency is common in HIV. This review outlines the epidemiology of vitamin D deficiency in HIV, summarizes our current understanding of the relationship between vitamin D and bone loss in HIV and the impact of vitamin D supplementation in this patient group.
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Novel Exercise Interventions to Improve Trunk Muscle Function: A Pilot Study

Ohio University
  • Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial.
    Trials (2016)
    Amano S, Ludin AF, Clift R, Nakazawa M, Law TD, Rush LJ, Manini TM, Thomas JS, Russ DW, Clark BC. Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial. Trials. 2016 Feb 12; 17:81.
    Abstract: Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the "cross-transfer" of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes).
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Perpheral mechanisms of fatigue in inflammatory arthritis

Vanderbilt University Medical Center
  • 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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Dynamic Inflammatory and Mood Predictors of Cognitive Aging in Bipolar Disorder

University of California San Diego
  • The temporal course and clinical correlates of subjective impulsivity in bipolar disorder as revealed through ecological momentary assessment.
    Journal of affective disorders (2016)
    Depp CA, Moore RC, Dev SI, Mausbach BT, Eyler LT, Granholm EL. The temporal course and clinical correlates of subjective impulsivity in bipolar disorder as revealed through ecological momentary assessment. J Affect Disord. 2016 Mar 15; 193:145-50.
    Abstract: Impulsivity is frequently linked with bipolar disorder and is associated with mania and negative outcomes. The temporal dynamics of subjective impulsivity are unclear, in particular whether impulsivity precedes or follows changes in positive or negative affect.
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Efficacy Study of Fluzone high Dose Vaccine Compared with Fluzone Vaccine in Elderly Adults

The Ohio State University
  • Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial.
    Clinical and vaccine immunology : CVI (2016)
    Dunning AJ, DiazGranados CA, Voloshen T, Hu B, Landolfi VA, Talbot HK. Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial. Clin Vaccine Immunol. 2016 Jan 13; 23(3):228-35.
    Abstract: Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus--the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.).
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  • Efficacy of high-dose versus standard-dose influenza vaccine in older adults.
    The New England journal of medicine (2014)
    DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14; 371(7):635-45.
    Abstract: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness.
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Identifying neural correlates of altruism

Georgetown University
  • Is costly punishment altruistic? Exploring rejection of unfair offers in the Ultimatum Game in real-world altruists.
    Scientific reports (2016)
    Brethel-Haurwitz KM, Stoycos SA, Cardinale EM, Huebner B, Marsh AA. Is costly punishment altruistic? Exploring rejection of unfair offers in the Ultimatum Game in real-world altruists. Sci Rep. 2016 Jan 7; 6:18974.
    Abstract: In the Ultimatum Game (UG), incurring a cost to punish inequity is commonly termed altruistic punishment. This behaviour is thought to benefit others if the defector becomes more equitable in future interactions. However, clear connections between punishment in the UG and altruistic behaviours outside the laboratory are lacking. We tested the altruistic punishment hypothesis in a sample of extraordinarily altruistic adults, predicting that if punishing inequity is predictive of altruism more broadly, extraordinary altruists should punish more frequently. Results showed that punishment was not more prevalent in extraordinary altruists than controls. However, a self-reported altruism measure previously linked to peer evaluations but not behaviour, and on which extraordinary altruists and controls did not differ, did predict punishment. These findings support suggestions that altruistic punishment in the UG is better termed costly punishment and may be motivated by social, but not necessarily prosocial, concerns. Results also support prior suggestions that self-reported altruism may not reliably predict altruistic behaviour.
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  • Neural and cognitive characteristics of extraordinary altruists.
    Proceedings of the National Academy of Sciences of the United States of America (2014)
    Marsh AA, Stoycos SA, Brethel-Haurwitz KM, Robinson P, VanMeter JW, Cardinale EM. Neural and cognitive characteristics of extraordinary altruists. Proc Natl Acad Sci U S A. 2014 Oct 21; 111(42):15036-41.
    Abstract: Altruistic behavior improves the welfare of another individual while reducing the altruist's welfare. Humans' tendency to engage in altruistic behaviors is unevenly distributed across the population, and individual variation in altruistic tendencies may be genetically mediated. Although neural endophenotypes of heightened or extreme antisocial behavior tendencies have been identified in, for example, studies of psychopaths, little is known about the neural mechanisms that support heightened or extreme prosocial or altruistic tendencies. In this study, we used structural and functional magnetic resonance imaging to assess a population of extraordinary altruists: altruistic kidney donors who volunteered to donate a kidney to a stranger. Such donations meet the most stringent definitions of altruism in that they represent an intentional behavior that incurs significant costs to the donor to benefit an anonymous, nonkin other. Functional imaging and behavioral tasks included face-emotion processing paradigms that reliably distinguish psychopathic individuals from controls. Here we show that extraordinary altruists can be distinguished from controls by their enhanced volume in right amygdala and enhanced responsiveness of this structure to fearful facial expressions, an effect that predicts superior perceptual sensitivity to these expressions. These results mirror the reduced amygdala volume and reduced responsiveness to fearful facial expressions observed in psychopathic individuals. Our results support the possibility of a neural basis for extraordinary altruism. We anticipate that these findings will expand the scope of research on biological mechanisms that promote altruistic behaviors to include neural mechanisms that support affective and social responsiveness.
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Neurocognitive effects of mild hypothyroidism

Oregon Health & Science University
  • Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition.
    Thyroid : official journal of the American Thyroid Association (2016)
    Samuels MH, Kolobova I, Smeraglio A, Peters D, Purnell JQ, Schuff KG. Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition. Thyroid. 2016 Mar; 26(3):347-55.
    Abstract: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition.
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  • The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition.
    The Journal of clinical endocrinology and metabolism (2014)
    Samuels MH, Kolobova I, Smeraglio A, Peters D, Janowsky JS, Schuff KG. The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition. J Clin Endocrinol Metab. 2014 Mar; 99(3):843-51.
    Abstract: TSH-suppressive doses of levothyroxine (L-T4) have adverse effects on bone and cardiac function, but it is unclear whether central nervous system function is also affected.
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EVALUATION OF A LIFESTYLE INTERVENTION FOR EMPLOYEES WITH PREDIABETES

The Ohio State University
  • A Randomized Controlled Trial Translating the Diabetes Prevention Program to a University Worksite, Ohio, 2012-2014.
    Preventing chronic disease (2015)
    Weinhold KR, Miller CK, Marrero DG, Nagaraja HN, Focht BC, Gascon GM. A Randomized Controlled Trial Translating the Diabetes Prevention Program to a University Worksite, Ohio, 2012-2014. Prev Chronic Dis. 2015 Nov 25; 12:E210.
    Abstract: Working adults spend much time at the workplace, an ideal setting for wellness programs targeting weight loss and disease prevention. Few randomized trials have evaluated the efficacy of worksite diabetes prevention programs. This study evaluated the efficacy of a worksite lifestyle intervention on metabolic and behavioral risk factors compared with usual care.
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  • Early weight-loss success identifies nonresponders after a lifestyle intervention in a worksite diabetes prevention trial.
    Journal of the Academy of Nutrition and Dietetics (2015)
    Miller CK, Nagaraja HN, Weinhold KR. Early weight-loss success identifies nonresponders after a lifestyle intervention in a worksite diabetes prevention trial. J Acad Nutr Diet. 2015 Sep; 115(9):1464-71.
    Abstract: People with prediabetes are at increased risk for developing type 2 diabetes mellitus. Weight reduction through lifestyle modification can significantly reduce diabetes risk. Yet, weight loss varies among individuals and some people do not achieve clinically meaningful weight loss after treatment.
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Renin-Angiotensin and Fibrinolysis Interaction in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis

Vanderbilt University Medical Center
  • 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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  • 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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Diabetes Self-Management

Duke University
  • Diabetes Learning in Virtual Environments: Testing the Efficacy of Self-Management Training and Support in Virtual Environments (Randomized Controlled Trial Protocol).
    Nursing research (2015)
    Vorderstrasse AA, Melkus GD, Pan W, Lewinski AA, Johnson CM. Diabetes Learning in Virtual Environments: Testing the Efficacy of Self-Management Training and Support in Virtual Environments (Randomized Controlled Trial Protocol). Nurs Res. 2015 Nov-Dec; 64(6):485-93.
    Abstract: Ongoing self-management improves outcomes for those with Type 2 diabetes (T2D); however, there are many barriers to patients receiving assistance in this from the healthcare system and peers. Findings from our pilot study showed that a virtual diabetes community on the Internet with real-time interaction among peers with T2D-and with healthcare professionals-is feasible and has the potential to influence clinical and psychosocial outcomes.
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"A phase 1 clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens utilizing recombinant adenovirus serotype 35 (rAd35) with HIV-1 clade A Env insert and recombinant adenovirus serotype 5 (rAd5) with HIV-1 clade A or B Env inserts in healthy, HIV-1-uninfected adults. (HVTN 083)"

Vanderbilt University Medical Center
  • 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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DAIRY FAT AS A MEDIATOR OF VITAMIN E ADEQUACY IN INDIVIDUALS WITH METABOLIC SYNDROME

The Ohio State University
  • α-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial.
    The American journal of clinical nutrition (2015)
    Mah E, Sapper TN, Chitchumroonchokchai C, Failla ML, Schill KE, Clinton SK, Bobe G, Traber MG, Bruno RS. α-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial. Am J Clin Nutr. 2015 Nov; 102(5):1070-80.
    Abstract: Increasing dietary fat intake is expected to improve α-tocopherol bioavailability, which could be beneficial for improving α-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary α-tocopherol requirements.
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PAR Regulation of Platelet Function in Diabetic Patients

Vanderbilt University Medical Center
  • 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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  • 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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  • Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.
    Molecular pharmacology (2013)
    Duvernay M, Young S, Gailani D, Schoenecker J, Hamm HE. Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets. Mol Pharmacol. 2013 Apr; 83(4):781-92.
    Abstract: With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.
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Effects of Interrupting Sedentary Behavior on Metabolic and Cognitive Outcomes in Children

NIH Clinical Center
  • Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial.
    The Journal of clinical endocrinology and metabolism (2015)
    Belcher BR, Berrigan D, Papachristopoulou A, Brady SM, Bernstein SB, Brychta RJ, Hattenbach JD, Tigner IL Jr, Courville AB, Drinkard BE, Smith KP, Rosing DR, Wolters PL, Chen KY, Yanovski JA. Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial. J Clin Endocrinol Metab. 2015 Oct; 100(10):3735-43.
    Abstract: Limited data suggest that interrupting sedentary behaviors with activity improves metabolic parameters in adults.
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SIP 9-11 Field-Testing and Validation of an Epilepsy Self-management Measurement Scale

Emory University
  • Development of the Adult Epilepsy Self-Management Measurement Instrument (AESMMI).
    Epilepsy & behavior : E&B (2015)
    Escoffery C, Bamps Y, LaFrance WC Jr, Stoll S, Shegog R, Buelow J, Shafer P, Thompson NJ, McGee RE, Hatfield K. Development of the Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015 Sep; 50:172-83.
    Abstract: Epilepsy self-management is the total sum of steps that people perform to maximize seizure control, to minimize the impact of having a seizure disorder, and to maximize quality of life. As part of a phased approach to instrument development, we conducted descriptive analyses of data from epilepsy self-management items covering 10 domains of self-management gathered from 422 adults with epilepsy from multiple study sites. Participants most frequently reported performing sets of behaviors related to managing treatment and stigma, information seeking, managing symptoms, and communicating with providers. Behaviors reported with lower frequency were related to seeking social support and engaging in wellness behaviors. Significant differences for the domains were found for income, gender, and education levels but not for other different demographic variables. A subsequent analytic phase, reported in a companion article, will use factor analysis to identify and validate the subscale structure of the domains.
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  • Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI).
    Epilepsy & behavior : E&B (2015)
    Escoffery C, Bamps Y, LaFrance WC Jr, Stoll S, Shegog R, Buelow J, Shafer P, Thompson NJ, McGee RE, Hatfield K. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015 Sep; 50:184-9.
    Abstract: The purpose of this study was to test the psychometric properties of an enhanced Adult Epilepsy Self-Management Measurement Instrument (AESMMI). An instrument of 113 items, covering 10 a priori self-management domains, was generated through a multiphase process, based on a review of the literature, validated epilepsy and other chronic condition self-management scales and expert input. Reliability and exploratory factor analyses were conducted on data collected from 422 adults with epilepsy. The instrument was reduced to 65 items, converging on 11 factors: Health-care Communication, Coping, Treatment Management, Seizure Tracking, Social Support, Seizure Response, Wellness, Medication Adherence, Safety, Stress Management, and Proactivity. Exploratory factors supported the construct validity for 6 a priori domains, albeit with significant changes in the retained items or in their scope and 3 new factors. One a priori domain was split in 2 subscales pertaining to treatment. The configuration of the 11 factors provides additional insight into epilepsy self-management behaviors. Internal consistency reliability of the 65-item instrument was high (α=.935). Correlations with independent measures of health status, quality of life, depression, seizure severity, and life impact of epilepsy further validated the instrument. This instrument shows potential for use in research and clinical settings and for assessing intervention outcomes and self-management behaviors in adults with epilepsy.
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Language and Cognition for Adults with Cochlear Implants

The Ohio State University
  • Word Recognition Variability With Cochlear Implants: "Perceptual Attention" Versus "Auditory Sensitivity".
    Ear and hearing (2016)
    Moberly AC, Lowenstein JH, Nittrouer S. Word Recognition Variability With Cochlear Implants: "Perceptual Attention" Versus "Auditory Sensitivity". Ear Hear. 2016 Jan-Feb; 37(1):14-26.
    Abstract: Cochlear implantation does not automatically result in robust spoken language understanding for postlingually deafened adults. Enormous outcome variability exists, related to the complexity of understanding spoken language through cochlear implants (CIs), which deliver degraded speech representations. This investigation examined variability in word recognition as explained by "perceptual attention" and "auditory sensitivity" to acoustic cues underlying speech perception.
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo controlled Trial of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder, the Polaris Trial

The Ohio State University
  • Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study.
    The Journal of clinical psychiatry (2015)
    Thase ME, Youakim JM, Skuban A, Hobart M, Zhang P, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015 Sep; 76(9):1232-40.
    Abstract: To evaluate efficacy, safety, and tolerability of brexpiprazole adjunctive to antidepressant treatments (ADTs) in patients with major depressive disorder (as defined by DSM-IV-TR criteria) with inadequate response to ADTs.
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MKC-TI-175: A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized, Clinical Trial Evaluating the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Technosphere® Inhalation Powder (Placebo) in Insulin Naïve Subjects With Type 2 Diabetes Mellitus Poorly Controlled With Oral Antidiabetic Agents Over a 24-week Treatment Period

Oregon Health & Science University
  • Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents.
    Diabetes care (2015)
    Rosenstock J, Franco D, Korpachev V, Shumel B, Ma Y, Baughman R, Amin N, McGill JB, Affinity 2 Study Group.. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care. 2015 Dec; 38(12):2274-81.
    Abstract: To investigate the efficacy and safety of prandial Technosphere inhaled insulin (TI), an inhaled insulin with a distinct time action profile, in insulin-naïve type 2 diabetes (T2D) inadequately controlled on oral antidiabetes agents (OADs).
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Structural and Functional Brain Aging in Bipolar Disorder (Renewal)

University of California San Diego
  • Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder.
    Journal of affective disorders (2015)
    Acheson DT, Eyler LT, Resovsky J, Tsan E, Risbrough VB. Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder. J Affect Disord. 2015 Oct 1; 185:230-8.
    Abstract: Affective dysregulation is a core feature of bipolar disorder (BD). Abnormalities in neural circuits underlying affect regulation have been observed in BD, specifically in the structure and function of the amygdala and orbital frontal cortex (OFC). Fear extinction is an automatic affect regulatory process relying on neural circuits that are abnormal in BD. Thus, fear extinction might be useful in probing automatic affect regulation deficits in BD. We tested the hypothesis that BD is associated with reduced ability to extinguish fear responses.
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  • Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar Patients.
    Journal of the International Neuropsychological Society : JINS (2015)
    McKenna BS, Theilmann RJ, Sutherland AN, Eyler LT. Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar Patients. J Int Neuropsychol Soc. 2015 May; 21(5):330-41.
    Abstract: Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD.
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  • Increased cerebral blood flow associated with better response inhibition in bipolar disorder.
    Journal of the International Neuropsychological Society : JINS (2015)
    Dev SI, McKenna BS, Sutherland AN, Shin DD, Liu TT, Wierenga CE, Eyler LT. Increased cerebral blood flow associated with better response inhibition in bipolar disorder. J Int Neuropsychol Soc. 2015 Feb; 21(2):105-15.
    Abstract: Impairment on inhibitory tasks has been well documented in bipolar disorder (BD). Differences in cerebral blood flow (CBF) between BD patients and healthy comparison (HC) participants have also been reported. Few studies have examined the relationship between cognitive performance and regional CBF in this patient population. We hypothesized that group differences on an inhibitory task (the Delis-Kaplan Executive Function Scale's Color-Word Inhibition task) would be associated with differential CBF in bilateral anterior cingulate cortex (ACC), inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants. Total gray matter (GM) CBF was measured, and regional CBF values were extracted for each region of interest (ROI) using Freesurfer-based individual parcellations. Group, CBF, and group-by-CBF interaction were examined as predictors of inhibition performance. Groups did not differ in age, gender or education. BD patients performed significantly worse on Color-Word inhibition. There were no significant group differences in CBF in either total GM or in any ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and right DLPFC such that better inhibitory performance was generally associated with higher resting state CBF in BD subjects, but not HC participants. Although CBF was not abnormal in this euthymic BD sample, results confirm previous reports of inter-episode inhibitory deficits and indicate that the perfusion-cognition relationship is different in BD compared to HC individuals.
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  • Brain functional correlates of working memory: reduced load-modulated activation and deactivation in aging without hyperactivation or functional reorganization.
    Journal of the International Neuropsychological Society : JINS (2014)
    Kaup AR, Drummond SP, Eyler LT. Brain functional correlates of working memory: reduced load-modulated activation and deactivation in aging without hyperactivation or functional reorganization. J Int Neuropsychol Soc. 2014 Oct; 20(9):945-50.
    Abstract: We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common.
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  • Associations between circadian activity rhythms and functional brain abnormalities among euthymic bipolar patients: a preliminary study.
    Journal of affective disorders (2014)
    McKenna BS, Drummond SP, Eyler LT. Associations between circadian activity rhythms and functional brain abnormalities among euthymic bipolar patients: a preliminary study. J Affect Disord. 2014 Aug; 164:101-6.
    Abstract: Working memory and underlying functional brain deficits have been observed in euthymic bipolar disorder (BD) patients, though there is heterogeneity in the degree of deficits. Sleep/circadian rhythm abnormalities are thought to be a core component of BD and may explain some of the heterogeneity in functional abnormalities. This preliminary study examined associations between sleep/circadian rhythm abnormalities and functional magnetic resonance imaging (fMRI) brain response on a working memory task among BD patients.
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  • Abnormalities of brain response during encoding into verbal working memory among euthymic patients with bipolar disorder.
    Bipolar disorders (2014)
    McKenna BS, Sutherland AN, Legenkaya AP, Eyler LT. Abnormalities of brain response during encoding into verbal working memory among euthymic patients with bipolar disorder. Bipolar Disord. 2014 May; 16(3):289-99.
    Abstract: Individuals with bipolar disorder (BD) have trait-like deficits in attention and working memory (WM). A fundamental dissociation for most verbal WM theories involves the separation of sensory-perceptual encoding, reliant upon attention, from the maintenance of this information in WM proper. The present study examined if patients with BD demonstrate differential neural changes in encoding and maintenance WM processes that underlie cognitive impairment.
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Effects of Asthma Therapeutics Targeting IL-13 on IL-17A Production in Women with Severe Asthma

Vanderbilt University Medical Center
  • 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.e1.
    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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Patient Centered Research

Vanderbilt University Medical Center
  • 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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  • 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..
    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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"Dietary Salt in Postural Tachycardia Syndrome"

Vanderbilt University Medical Center
  • 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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Effect of food order on postprandial glucose and insulin levels in overweight/obese subjects with type 2 diabetes

Weill Cornell Medical College
  • Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels.
    Diabetes care (2015)
    Shukla AP, Iliescu RG, Thomas CE, Aronne LJ. Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels. Diabetes Care. 2015 Jul; 38(7):e98-9.
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FLuctuATion reduction with inSUlin and Glp-1 Added togetheR (FLAT-SUGAR)

Oregon Health & Science University
  • Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.
    Diabetes care (2015)
    FLAT-SUGAR Trial Investigators., Probstfield JL, Hirsch I, O'Brien K, Davis B, Bergenstal R, Kingry C, Khakpour D, Pressel S, Branch KR, Riddle M. Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes. Diabetes Care. 2015 Aug; 38(8):1558-66.
    Abstract: Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested.
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Technology to Enhance Treatment for Early Conduct Problems in Low Income Families

University of North Carolina at Chapel Hill
  • Socioeconomic status, parenting, and externalizing problems in African American single-mother homes: A person-oriented approach.
    Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) (2015)
    Anton MT, Jones DJ, Youngstrom EA. Socioeconomic status, parenting, and externalizing problems in African American single-mother homes: A person-oriented approach. J Fam Psychol. 2015 Jun; 29(3):405-15.
    Abstract: African American youth, particularly those from single-mother homes, are overrepresented in statistics on externalizing problems. The family is a central context in which to understand externalizing problems; however, reliance on variable-oriented approaches to the study of parenting, which originate from work with intact, middle-income, European American families, may obscure important information regarding variability in parenting styles among African American single mothers, and in turn, variability in youth outcomes as well. The current study demonstrated that within African American single-mother families: (a) a person-, rather than variable-, oriented approach to measuring parenting style may further elucidate variability; (b) socioeconomic status may provide 1 context within which to understanding variability in parenting style; and (c) 1 marker of socioeconomic status, income, and parenting style may each explain variability in youth externalizing problems; however, the interaction between income and parenting style was not significant. Findings have potential implications for better understanding the specific contexts in which externalizing problems may be most likely to occur within this at-risk and underserved group.
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Imaging genetics of spasmodic dysphonia

Mount Sinai School of Medicine
  • Alcohol responsiveness in laryngeal dystonia: a survey study.
    Journal of neurology (2015)
    Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol. 2015 Jun; 262(6):1548-56.
    Abstract: Laryngeal dystonia (LD) is a task-specific focal dystonia of unknown pathophysiology affecting speech production. We examined the demographics of anecdotally reported alcohol use and its effects on LD symptoms using an online survey based on Research Electronic Data Capture (REDCap™) and National Spasmodic Dysphonia Association's patient registry. From 641 participants, 531 were selected for data analysis, and 110 were excluded because of unconfirmed diagnosis. A total of 406 patients (76.5 %) had LD and 125 (23.5 %) had LD and voice tremor (LD/VT). The consumption of alcohol was reported by 374 LD (92.1 %) and 109 LD/VT (87.2 %) patients. Improvement of voice symptoms after alcohol ingestion was noted by 227 LD (55.9 % of all patients) and 73 LD/VT (58.4 %), which paralleled the improvement observed by patient's family and/or friends in 214 LD (57.2 %) and 69 LD/VT (63.3 %) patients. The benefits lasted 1-3 h in both groups with the maximum effect after 2 drinks in LD patients (p = 0.002), whereas LD/VT symptoms improved independent of the consumed amount (p = 0.48). Our data suggest that isolated dystonic symptoms, such as in LD, are responsive to alcohol intake and this responsiveness is not attributed to the presence of VT, which is known to have significant benefits from alcohol ingestion. Alcohol may modulate the pathophysiological mechanisms underlying abnormal neurotransmission of γ-aminobutyric acid (GABA) in dystonia and as such provide new avenues for novel therapeutic options in these patients.
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Effect of Chewing Gum on Tooth Sensitivity Associated with Tooth Whitening: A Pilot Study

The Ohio State University
  • The effect of gum chewing on sensitivity associated with in-office whitening procedures.
    International journal of dental hygiene (2015)
    Henry RK, Carkin M. The effect of gum chewing on sensitivity associated with in-office whitening procedures. Int J Dent Hyg. 2015 Nov; 13(4):308-14.
    Abstract: Tooth sensitivity is the most common side effect of in-office tooth-whitening procedures. The purpose of this study was to determine whether chewing gum containing 0.6% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) before tooth whitening would reduce tooth sensitivity during an in-office whitening procedure.
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A5311 - Phase 1 Clinical Trial of the Pharmacokinetics of High Dose Daily Rifapentine, Given as a Single Dose or in Divided Doses to Healthy Volunteers

Vanderbilt University Medical Center
  • 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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Pathophysiology of Cardiometabolic Risk Factors in African Americans

Vanderbilt University Medical Center
  • 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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MRI Biomarkers and Genetic Risk Factors of Alzheimer Disease in Down Syndrome

Vanderbilt University Medical Center
  • 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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  • 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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A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events

Weill Cornell Medical College
  • LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations.
    Diabetes, obesity & metabolism (2015)
    Daniels GH, Hegedüs L, Marso SP, Nauck MA, Zinman B, Bergenstal RM, Mann JF, Derving Karsbøl J, Moses AC, Buse JB, Tuttle RM, LEADER Trial Investigators.. LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations. Diabetes Obes Metab. 2015 May; 17(5):477-86.
    Abstract: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization.
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  • LEADER 3--lipase and amylase activity in subjects with type 2 diabetes: baseline data from over 9000 subjects in the LEADER Trial.
    Pancreas (2014)
    Steinberg WM, Nauck MA, Zinman B, Daniels GH, Bergenstal RM, Mann JF, Steen Ravn L, Moses AC, Stockner M, Baeres FM, Marso SP, Buse JB, LEADER Trial investigators.. LEADER 3--lipase and amylase activity in subjects with type 2 diabetes: baseline data from over 9000 subjects in the LEADER Trial. Pancreas. 2014 Nov; 43(8):1223-31.
    Abstract: This report from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial describes baseline lipase and amylase activity in type 2 diabetic subjects without acute pancreatitis symptoms before randomization to the glucagonlike peptide analog liraglutide or placebo.
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  • Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.
    American heart journal (2013)
    Marso SP, Poulter NR, Nissen SE, Nauck MA, Zinman B, Daniels GH, Pocock S, Steinberg WM, Bergenstal RM, Mann JF, Ravn LS, Frandsen KB, Moses AC, Buse JB. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013 Nov; 166(5):823-30.e5.
    Abstract: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM).
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The TrialNet Natural History Study of the Development of Type 1 Diabetes

University of Minnesota
  • β cell death and dysfunction during type 1 diabetes development in at-risk individuals.
    The Journal of clinical investigation (2015)
    Herold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, Ledizet M, Sosenko JM, Krischer JP, Palmer JP, Type 1 Diabetes TrialNet Study Group.. β cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest. 2015 Mar 2; 125(3):1163-73.
    Abstract: Role of the funding source: Funding from the NIH was used for support of the participating clinical centers and the coordinating center. The funding source did not participate in the collection or the analysis of the data.
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Parent Protocol: Studies of the Etiology of Rheumatoid Arthritis (SERA) Project

University of Colorado Denver
  • Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis.
    The Journal of rheumatology (2015)
    Gan RW, Trouw LA, Shi J, Toes RE, Huizinga TW, Demoruelle MK, Kolfenbach JR, Zerbe GO, Deane KD, Edison JD, Gilliland WR, Norris JM, Holers VM. Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis. J Rheumatol. 2015 Apr; 42(4):572-9.
    Abstract: Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.
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  • Prevention of rheumatic diseases: strategies, caveats, and future directions.
    Rheumatic diseases clinics of North America (2014)
    Finckh A, Deane KD. Prevention of rheumatic diseases: strategies, caveats, and future directions. Rheum Dis Clin North Am. 2014 Nov; 40(4):771-85.
    Abstract: Rheumatic diseases affect a significant portion of the population and lead to increased health care costs, disability, and premature mortality; effective preventive measures for these diseases could lead to substantial improvements in public health. Natural history studies show that for most rheumatic diseases there is a period of preclinical disease development during which abnormal biomarkers or other processes can be detected. These changes are useful to understand mechanisms of disease pathogenesis; in addition, they may be applied to estimate a personal risk of future disease while individuals are still relatively asymptomatic and ultimately be used to identify individuals who may be targeted for preventive interventions.
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  • Preclinical rheumatoid arthritis (autoantibodies): an updated review.
    Current rheumatology reports (2014)
    Deane KD. Preclinical rheumatoid arthritis (autoantibodies): an updated review. Curr Rheumatol Rep. 2014 May; 16(5):419.
    Abstract: Multiple studies demonstrate that there is a period of development of rheumatoid arthritis (RA) during which there are elevations of disease-related biomarkers, including autoantibodies, in the absence of and prior to the development of RA; this period can be termed 'preclinical RA'. These 'preclinical' autoantibodies including rheumatoid factor and antibodies to citrullinated protein antigens, and more recent studies have also identified additional autoantibodies and a wide range of inflammatory biomarkers. These findings in conjunction with established and emerging data about genetic and environmental risk factors for RA support a model of disease development where certain factors lead to an initial triggering of RA-related autoimmunity that expands over time to the point where symptomatic arthritis classifiable as RA develops. Herein will be reviewed updates in the field, as well as a discussion of current limitations of our understanding of preclinical RA, and potential future directions for study.
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  • Determinants of mortality among postmenopausal women in the women's health initiative who report rheumatoid arthritis.
    Arthritis & rheumatology (Hoboken, N.J.) (2014)
    Kuller LH, Mackey RH, Walitt BT, Deane KD, Holers VM, Robinson WH, Sokolove J, Chang Y, Liu S, Parks CG, Wright NC, Moreland LW. Determinants of mortality among postmenopausal women in the women's health initiative who report rheumatoid arthritis. Arthritis Rheumatol. 2014 Mar; 66(3):497-507.
    Abstract: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated peptide (anti-CCP) antibody levels and determined use of disease-modifying antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI). Using these data, we undertook this study to assess total mortality over 10 years of followup among white, black, or Hispanic women with self-reported RA in the WHI.
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  • Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease.
    Arthritis and rheumatism (2013)
    Willis VC, Demoruelle MK, Derber LA, Chartier-Logan CJ, Parish MC, Pedraza IF, Weisman MH, Norris JM, Holers VM, Deane KD. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 2013 Oct; 65(10):2545-54.
    Abstract: To evaluate the generation of rheumatoid arthritis (RA)-related autoantibodies in the lung.
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  • Relatives without rheumatoid arthritis show reactivity to anti-citrullinated protein/peptide antibodies that are associated with arthritis-related traits: studies of the etiology of rheumatoid arthritis.
    Arthritis and rheumatism (2013)
    Young KA, Deane KD, Derber LA, Hughes-Austin JM, Wagner CA, Sokolove J, Weisman MH, Buckner JH, Mikuls TR, O'Dell JR, Keating RM, Gregersen PK, Robinson WH, Holers VM, Norris JM. Relatives without rheumatoid arthritis show reactivity to anti-citrullinated protein/peptide antibodies that are associated with arthritis-related traits: studies of the etiology of rheumatoid arthritis. Arthritis Rheum. 2013 Aug; 65(8):1995-2004.
    Abstract: To examine reactivity to anti-citrullinated protein/peptide antibodies (ACPAs) and determine associations between ACPAs and other rheumatoid arthritis (RA)-related autoantibodies and clinically assessed swollen or tender joints in unaffected first-degree relatives of RA patients.
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  • Performance of anti-cyclic citrullinated Peptide assays differs in subjects at increased risk of rheumatoid arthritis and subjects with established disease.
    Arthritis and rheumatism (2013)
    Demoruelle MK, Parish MC, Derber LA, Kolfenbach JR, Hughes-Austin JM, Weisman MH, Gilliland W, Edison JD, Buckner JH, Mikuls TR, O'Dell JR, Keating RM, Gregersen PK, Norris JM, Holers VM, Deane KD. Performance of anti-cyclic citrullinated Peptide assays differs in subjects at increased risk of rheumatoid arthritis and subjects with established disease. Arthritis Rheum. 2013 Sep; 65(9):2243-52.
    Abstract: To compare the diagnostic accuracy and agreement of commonly available assays for anti-citrullinated protein antibodies in patients with established rheumatoid arthritis (RA) and subjects at increased risk of RA.
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The effects of Fish Oil and Aspirin on Cardiovascular Risk in Type 2 Diabetes

University of Rochester
  • The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA.
    Prostaglandins, leukotrienes, and essential fatty acids (2015)
    Block RC, Abdolahi A, Tu X, Georas SN, Brenna JT, Phipps RP, Lawrence P, Mousa SA. The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA. Prostaglandins Leukot Essent Fatty Acids. 2015 May; 96:17-24.
    Abstract: Aspirin's prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin's effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a "V"-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu.
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  • The effects of aspirin and fish oil consumption on lysophosphatidylcholines and lysophosphatidic acids and their correlates with platelet aggregation in adults with diabetes mellitus.
    Prostaglandins, leukotrienes, and essential fatty acids (2014)
    Abdolahi A, Georas SN, Brenna JT, Cai X, Thevenet-Morrison K, Phipps RP, Lawrence P, Mousa SA, Block RC. The effects of aspirin and fish oil consumption on lysophosphatidylcholines and lysophosphatidic acids and their correlates with platelet aggregation in adults with diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2014 Feb-Mar; 90(2-3):61-8.
    Abstract: Many diabetics are insensitive to aspirin's platelet anti-aggregation effects. The influence of co-administration of aspirin and fish oil (FO) on plasma lysophospholipids in subjects with diabetes is poorly characterized. Thirty adults with type 2 diabetes mellitus were treated with aspirin (81mg/day) for seven days, then with FO (4g/day) for 28 days, then in combination for another seven days. Lysophospholipids and platelet measures were determined after acute (4h) and chronic (7 days) ingestion of aspirin, FO, or both in combination. FO ingestion reduced all lysophosphatidic acid (LPA) concentrations, while EPA (20:5n-3) and DHA (22:6n-3) lysophosphatidylcholine (LPC) concentrations significantly increased after FO alone and in combination with aspirin. In vitro arachidonic acid-induced platelet aggregation was most strongly correlated with palmitoleic (16:1) and oleic (18:1) LPA and LPC concentrations at all time points. The ingestion of these agents may reduce cardiovascular disease risk in diabetic adults, with a disrupted lipid milieu, via lysolipid mediated mechanisms.
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  • Effects of low-dose aspirin and fish oil on platelet function and NF-kappaB in adults with diabetes mellitus.
    Prostaglandins, leukotrienes, and essential fatty acids (2013)
    Block RC, Abdolahi A, Smith B, Meednu N, Thevenet-Morrison K, Cai X, Cui H, Mousa S, Brenna JT, Georas S. Effects of low-dose aspirin and fish oil on platelet function and NF-kappaB in adults with diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2013 Jul; 89(1):9-18.
    Abstract: Many diabetics are insensitive to aspirin's platelet anti-aggregation effects. The possible modulating effects of co-administration of aspirin and fish oil in subjects with diabetes are poorly characterized.
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A Reduced Carbohydrate Diet Intervention for PCOS

The University of Alabama at Birmingham
  • A lower-carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes.
    The Journal of nutrition (2015)
    Gower BA, Goss AM. A lower-carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes. J Nutr. 2015 Jan; 145(1):177S-83S.
    Abstract: Obesity, particularly visceral and ectopic adiposity, increases the risk of type 2 diabetes.
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Community Partnership to Reduce the Diabetes/Obesity Burden among African-American Women in Nashville, TN

Meharry Medical College
  • Identification of patient-centered outcomes among African American women with type 2 diabetes.
    Diabetes research and clinical practice (2014)
    Miller ST, Akohoue SA, Brooks MA. Identification of patient-centered outcomes among African American women with type 2 diabetes. Diabetes Res Clin Pract. 2014 Dec; 106(3):487-90.
    Abstract: African American women carry a disproportionate diabetes burden, yet there is limited information on strategies to identify outcomes women perceive as important intervention outcomes (patient-centered outcomes). This study presents a brief strategy to solicit these outcomes and to describe outcomes identified using the highlighted strategy.
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Assessment of Hyperphagia in Patients with Pseudohypoparathyroidism

Vanderbilt University Medical Center
  • 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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Determining Efficacy of a Tolerable Means of Strengthening for Older Adults With Knee Osteoarthritis: Partial Blood Flow Restriction Low Intensity Resistance Training

University of Iowa
  • Efficacy of blood flow-restricted, low-load resistance training in women with risk factors for symptomatic knee osteoarthritis.
    PM & R : the journal of injury, function, and rehabilitation (2015)
    Segal NA, Williams GN, Davis MC, Wallace RB, Mikesky AE. Efficacy of blood flow-restricted, low-load resistance training in women with risk factors for symptomatic knee osteoarthritis. PM R. 2015 Apr; 7(4):376-84.
    Abstract: To assess whether concurrent blood flow restriction (BFR) during low-load resistance training is an efficacious and tolerable means of improving quadriceps strength and volume in women with risk factors for symptomatic knee osteoarthritis (OA).
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Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers

NIH Clinical Center
  • A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.
    Genes, brain, and behavior (2014)
    Lenroot RK, Blumenthal JD, Wallace GL, Clasen LS, Lee NR, Giedd JN. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome. Genes Brain Behav. 2014 Nov; 13(8):841-9.
    Abstract: Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample.
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Vitamin D and type 2 diabetes

Northwestern University
  • Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial.
    Diabetes care (2014)
    Pittas AG, Dawson-Hughes B, Sheehan PR, Rosen CJ, Ware JH, Knowler WC, Staten MA, D2d Research Group.. Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial. Diabetes Care. 2014 Dec; 37(12):3227-34.
    Abstract: Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes.
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Psychobiological Investigation of Socioemotional Functioning in Autism

Vanderbilt University Medical Center
  • 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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  • Biobehavioral profiles of arousal and social motivation in autism spectrum disorders.
    Journal of child psychology and psychiatry, and allied disciplines (2014)
    Corbett BA, Swain DM, Newsom C, Wang L, Song Y, Edgerton D. Biobehavioral profiles of arousal and social motivation in autism spectrum disorders. J Child Psychol Psychiatry. 2014 Aug; 55(8):924-34.
    Abstract: Children with autism spectrum disorder (ASD) are impaired in social communication and interaction with peers, which may reflect diminished social motivation. Many children with ASD show enhanced stress when playing with other children. This study investigated social and stress profiles of children with ASD during play.
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  • Examining associations between anxiety and cortisol in high functioning male children with autism.
    Journal of neurodevelopmental disorders (2013)
    Simon DM, Corbett BA. Examining associations between anxiety and cortisol in high functioning male children with autism. J Neurodev Disord. 2013 Nov 11; 5(1):32.
    Abstract: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal.
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Neurocognitive Intervention and Supportive Therapy in Individuals with Parkinson's Disease and Their Support Persons

Virginia Commonwealth University
  • A-51Preliminary Outcome Data of a Clinical Trial Comparing a Neurocognitive Intervention to Supportive Therapy in Individuals with Parkinson's Disease.
    Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists (2014)
    Lageman S, Cash T, Mickens M. A-51Preliminary Outcome Data of a Clinical Trial Comparing a Neurocognitive Intervention to Supportive Therapy in Individuals with Parkinson's Disease. Arch Clin Neuropsychol. 2014 Sep; 29(6):522.
    Abstract: The goal of this study is to evaluate the effects of a neurocognitive rehabilitation intervention compared to a supportive therapy condition in individuals with Parkinson's disease (PD).
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Pharmacogenetics of ACE Inhibitor-Associated Angioedema: Aim 1 (NIH)

Vanderbilt University Medical Center
  • 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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  • 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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Psychosis and Aging

University of California San Diego
  • Wellness within illness: happiness in schizophrenia.
    Schizophrenia research (2014)
    Palmer BW, Martin AS, Depp CA, Glorioso DK, Jeste DV. Wellness within illness: happiness in schizophrenia. Schizophr Res. 2014 Oct; 159(1):151-6.
    Abstract: Schizophrenia is typically a chronic disorder and among the most severe forms of serious mental illnesses in terms of adverse impact on quality of life. Yet, there have been suggestions that some people with schizophrenia can experience an overall sense of happiness in their lives. We investigated happiness among 72 outpatients with non-remitted chronic schizophrenia with a mean duration of illness of 24.4 years, and 64 healthy comparison subjects (HCs). Despite continued treatment with antipsychotic medications, the individuals with schizophrenia manifested a mild to moderate level of psychopathology. People with schizophrenia reported lower mean levels of happiness than HCs, but there was substantial heterogeneity within the schizophrenia group. Level of happiness in persons with schizophrenia was significantly correlated with higher mental health-related quality of life, and several positive psychosocial factors (lower perceived stress, and higher levels of resilience, optimism, and personal mastery). However, level of happiness was not related to sociodemographic characteristics, duration of illness, severity of positive or negative symptoms, physical function, medical comorbidity, or cognitive functioning. Except for an absence of an association with resilience, the pattern of correlations of happiness with other variables seen among HCs was similar to that in individuals with schizophrenia. Although happiness may be harder to achieve in the context of a serious mental illness, it nonetheless appears to be a viable treatment goal in schizophrenia. Psychotherapies targeting positive coping factors such as resilience, optimism, and personal mastery warrant further investigation.
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A phase 3, twelve-week, multicenter, double-blind, randomized, placebo-controlled, efficacy and safety study of Mesafem (Paroxetine Mesylate) capsules in the treatment of vasomotor symptoms associated with menopause

University Hospitals Cleveland Medical Center
  • Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause.
    Menopause (New York, N.Y.) (2015)
    Pinkerton JV, Joffe H, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015 Jan; 22(1):50-8.
    Abstract: Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated.
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  • Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause.
    Menopause (New York, N.Y.) (2014)
    Portman DJ, Kaunitz AM, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause. Menopause. 2014 Oct; 21(10):1082-90.
    Abstract: Two phase 3, randomized, placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms (VMS) associated with menopause and had a favorable tolerability profile. The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis.
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  • Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials.
    Menopause (New York, N.Y.) (2013)
    Simon JA, Portman DJ, Kaunitz AM, Mekonnen H, Kazempour K, Bhaskar S, Lippman J. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013 Oct; 20(10):1027-35.
    Abstract: The efficacy and safety of low-dose paroxetine 7.5 mg for the treatment of menopausal vasomotor symptoms were evaluated in two multicenter, double-blind, placebo-controlled, phase 3 studies of 12 and 24 weeks' duration.
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Brain Structure and Function in Children, Adolescents, and Young Adults at Risk for Huntington’s Disease

University of Iowa
  • Rhes suppression enhances disease phenotypes in Huntington's disease mice.
    Journal of Huntington's disease (2014)
    Lee JH, Sowada MJ, Boudreau RL, Aerts AM, Thedens DR, Nopoulos P, Davidson BL. Rhes suppression enhances disease phenotypes in Huntington's disease mice. J Huntingtons Dis. 2014; 3(1):65-71.
    Abstract: In Huntington's disease (HD) mutant HTT is ubiquitously expressed yet the striatum undergoes profound early degeneration. Cell culture studies suggest that a striatal-enriched protein, Rhes, may account for this vulnerability. We investigated the therapeutic potential of silencing Rhes in vivo using inhibitory RNAs (miRhes). While Rhes suppression was tolerated in wildtype mice, it failed to improve rotarod function in two distinct HD mouse models. Additionally, miRhes treated HD mice had increased anxiety-like behaviors and enhanced striatal atrophy as measured by longitudinal MRI when compared to control treated mice. These findings raise caution regarding the long-term implementation of inhibiting Rhes as a therapy for HD.
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  • Managing juvenile Huntington's disease.
    Neurodegenerative disease management (2013)
    Quarrell OW, Nance MA, Nopoulos P, Paulsen JS, Smith JA, Squitieri F. Managing juvenile Huntington's disease. Neurodegener Dis Manag. 2013 Jun 1; 3(3):.
    Abstract: Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.
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  • Measures of growth in children at risk for Huntington disease.
    Neurology (2012)
    Lee JK, Mathews K, Schlaggar B, Perlmutter J, Paulsen JS, Epping E, Burmeister L, Nopoulos P. Measures of growth in children at risk for Huntington disease. Neurology. 2012 Aug 14; 79(7):668-74.
    Abstract: The effect of mHTT on human development was examined by evaluating measures of growth in children at risk for Huntington disease (HD).
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  • Correlation of CAG repeat length between the maternal and paternal allele of the Huntingtin gene: evidence for assortative mating.
    Behavioral and brain functions : BBF (2011)
    Nopoulos P, Epping EA, Wassink T, Schlaggar BL, Perlmutter J. Correlation of CAG repeat length between the maternal and paternal allele of the Huntingtin gene: evidence for assortative mating. Behav Brain Funct. 2011 Oct 18; 7:45.
    Abstract: Triplet repeats contribute to normal variation in behavioral traits and when expanded, cause brain disorders. While Huntington's Disease is known to be caused by a CAG triplet repeat in the gene Huntingtin, the effect of CAG repeats on brain function below disease threshold has not been studied. The current study shows a significant correlation between the CAG repeat length of the maternal and paternal allele in the Huntingtin gene among healthy subjects, suggesting assortative mating.
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Systolic Blood Pressure Intervention Trial (SPRINT)

Emory University
  • Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.
    Kidney international (2015)
    Langefeld CD, Divers J, Pajewski NM, Hawfield AT, Reboussin DM, Bild DE, Kaysen GA, Kimmel PL, Raj DS, Ricardo AC, Wright JT Jr, Sedor JR, Rocco MV, Freedman BI, Systolic Blood Pressure Intervention Trial (SPRINT).. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial. Kidney Int. 2015 Jan; 87(1):169-75.
    Abstract: Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.
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  • The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).
    Clinical trials (London, England) (2014)
    Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, Fine LJ, Goff DC Jr, Johnson KC, Killeen AA, Lewis CE, Oparil S, Reboussin DM, Rocco MV, Snyder JK, Williamson JD, Wright JT Jr, Whelton PK, SPRINT Study Research Group.. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014 Oct; 11(5):532-46.
    Abstract: High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial.
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Cross-sectional Observational Study to Determine the Thermogenic Effect of Food in Children with Melanocortin Obesity Syndrome

Vanderbilt University Medical Center
  • 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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  • Energy expenditure in obese children with pseudohypoparathyroidism type 1a.
    International journal of obesity (2005) (2013)
    Shoemaker AH, Lomenick JP, Saville BR, Wang W, Buchowski MS, Cone RD. Energy expenditure in obese children with pseudohypoparathyroidism type 1a. Int J Obes (Lond). 2013 Aug; 37(8):1147-53.
    Abstract: Patients with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. The abnormality in energy expenditure and/or energy intake responsible for this weight gain is unknown.
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Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?

Stanford University
  • Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study.
    Diabetes care (2014)
    Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Ochoa H, Reaven G. Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes Care. 2014 Jul; 37(7):1944-50.
    Abstract: Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance.
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"A5306 - A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, together with Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin" (

Vanderbilt University Medical Center
  • 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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ACTG 5306, VERSION 1.0 DATED FEBRUARY 3, 2012: A PHASE I, THREE-ARM SAFETY, TOLERABILITY, AND PHARMACOKINETIC INTERACTION STUDY OF PA-824, AN INVESTIGATIONAL NITROIMIDAZOLE FOR THE TREATMENT OF TUBERCULOSIS, TOGETHER WITH EFAVIRENZ, RITONAVIR-BOOSTED LOPINAVIR, OR RIFAMPIN

The Ohio State University
  • 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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Evaluation of Internalized Stigmatization in Patients with Irritable Bowel Syndrome (IBS)

Northwestern University
  • Moving beyond perceptions: internalized stigma in the irritable bowel syndrome.
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (2014)
    Taft TH, Riehl ME, Dowjotas KL, Keefer L. Moving beyond perceptions: internalized stigma in the irritable bowel syndrome. Neurogastroenterol Motil. 2014 Jul; 26(7):1026-35.
    Abstract: Internalized stigma (IS) is an important construct in the chronic illness literature with implications for several patient reported outcomes. To date, no study exists evaluating IS in patients with the irritable bowel syndrome (IBS).
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Inflammation and Insulin Resistance in Rheumatoid Arthritis

Vanderbilt University Medical Center
  • 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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  • Insulin resistance is associated with increased concentrations of NT-proBNP in rheumatoid arthritis: IL-6 as a potential mediator.
    Inflammation (2014)
    Bradham WS, Ormseth MJ, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM. Insulin resistance is associated with increased concentrations of NT-proBNP in rheumatoid arthritis: IL-6 as a potential mediator. Inflammation. 2014 Jun; 37(3):801-8.
    Abstract: We examined the hypothesis that insulin resistance (IR) decreases circulating concentrations of N-terminal (NT)-probrain natriuretic peptide (BNP). Obesity, despite being a risk factor for heart failure (HF), is paradoxically associated with lower concentrations of BNP, a marker of myocardial stress. Low BNP in obesity is postulated to be due to IR; however, it has been difficult to define the role of IR independent of obesity. IR in rheumatoid arthritis (RA) is increased, independent of obesity, thus allowing potential mechanistic insights into the relationship between IR and BNP. We measured demographic factors, traditional cardiovascular risk factors, body mass index (BMI), markers of inflammation (interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor α (TNFα)), NT-proBNP, and IR by the homeostatic model assessment (HOMA) in 140 patients with RA and 82 control subjects. Patients with heart failure and coronary artery disease were excluded. We used multiple linear regression models to examine the relationship between HOMA and NT-proBNP in RA and controls and in RA alone, the additional effect of inflammation. As previously reported, NT-proBNP concentrations were higher in RA (median 80.49 pg/mL, IQR (23.67-167.08 pg/mL)) than controls (17.84 pg/mL (3.28-36.28 pg/mL)) (P < 0.001), and the prevalence of IR, defined by HOMA > 2.114, was higher among RA than controls (53 % vs. 15%, P > 0.001). HOMA was positively correlated with NT-proBNP (rho = 0.226, P = 0.007) in RA, but not in controls (rho = -0.154, P = 0.168). In a multivariable model adjusted for age, race, and sex, we found that increasing HOMA was statistically associated with increasing NT-proBNP concentrations in RA (P = 0.001), but not controls (P = 0.543) (P for interaction = 0.036). In RA subjects, when IL-6 was further included in the model, IL-6 (P = 0.0014), but not HOMA (P = 0.43), remained significantly associated with NT-proBNP, suggesting that IL-6 may be mechanistically involved in the relationship between IR and NT-proBNP in RA. We conclude that in patients with RA, insulin resistance is associated with higher, rather than the expected lower, concentrations of NT-proBNP and that this may be related to increased IL-6.
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  • Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial.
    Arthritis research & therapy (2013)
    Ormseth MJ, Oeser AM, Cunningham A, Bian A, Shintani A, Solus J, Tanner S, Stein CM. Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial. Arthritis Res Ther. 2013; 15(5):R110.
    Abstract: Rheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.
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  • Inflammation and hypertension in rheumatoid arthritis.
    The Journal of rheumatology (2013)
    Manavathongchai S, Bian A, Rho YH, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM. Inflammation and hypertension in rheumatoid arthritis. J Rheumatol. 2013 Nov; 40(11):1806-11.
    Abstract: Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.
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  • Association of epicardial adipose tissue with cardiometabolic risk and metabolic syndrome in patients with rheumatoid arthritis.
    Arthritis care & research (2013)
    Ormseth MJ, Lipson A, Alexopoulos N, Hartlage GR, Oeser AM, Bian A, Gebretsadik T, Shintani A, Raggi P, Stein CM. Association of epicardial adipose tissue with cardiometabolic risk and metabolic syndrome in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013 Sep; 65(9):1410-5.
    Abstract: Patients with rheumatoid arthritis (RA) have increased coronary atherosclerosis possibly related to increased prevalence of visceral adiposity, insulin resistance, and metabolic syndrome. Epicardial adipose tissue (EAT), a type of visceral fat, may contribute to cardiometabolic risk. The aim of this study was to measure EAT volume in patients with RA and determine its relationship with cardiometabolic risk markers and coronary artery calcium.
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  • Free fatty acids are associated with metabolic syndrome and insulin resistance but not inflammation in systemic lupus erythematosus.
    Lupus (2013)
    Ormseth MJ, Swift LL, Fazio S, Linton MF, Raggi P, Solus JF, Oeser A, Bian A, Gebretsadik T, Shintani A, Stein CM. Free fatty acids are associated with metabolic syndrome and insulin resistance but not inflammation in systemic lupus erythematosus. Lupus. 2013 Jan; 22(1):26-33.
    Abstract: Free fatty acids (FFAs) are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines promote lipolysis and increase FFAs, a cause of endothelial dysfunction and increased atherosclerosis risk. We hypothesized that increased inflammation is associated with increased FFAs, resulting in insulin resistance and atherosclerosis in patients with systemic lupus erythematosus (SLE). We measured clinical variables, serum FFAs, homeostasis model assessment for insulin resistance (HOMA), inflammatory cytokines, markers of endothelial activation, cholesterol concentrations and coronary artery calcium in 156 patients with SLE and 90 controls. We compared FFAs in patients with SLE and controls using Wilcoxon rank sum tests and further tested for the independent association between FFAs and disease status with adjustment for age, race and sex using multivariable regression models. We assessed the relationship between FFAs and continuous variables of interest using Spearman correlation and multivariable regression analysis. Levels of FFAs were higher in patients with SLE than controls (0.55 mmol/l (0.37-0.71) vs 0.44 mmol/l (0.32-0.60), P = 0.02). Levels of FFAs remained significantly higher among patients with SLE after adjustment for age, race and sex (P = 0.03) but not after further adjustment for body mass index (P = 0.13). FFA levels did not differ according to the usage of current immunosuppressive medications in univariate and adjusted analysis (all P > 0.05). Among patients with SLE, concentrations of FFAs were higher among those with metabolic syndrome compared to those without (0.66 mmol/l (0.46-0.81) vs 0.52 mmol/l (0.35-0.66), P < 0.001). FFAs were positively correlated with insulin resistance (HOMA) (rho = 0.23, P = 0.004, P adjusted = 0.006) and triglyceride levels (rho = 0.22, P = 0.01, P adjusted = 0.004). FFAs were not associated with inflammatory cytokines (IL-6, TNF-α) (all P > 0.05) but were positively associated with levels of E-selectin (rho = 0.33, P = < 0.001, P adjusted = 0.001) and ICAM-1 (rho = 0.35, P < 0.001, P adjusted = 0.001). FFAs were correlated with coronary artery calcium score (rho = 0.20, P = 0.01) but this was attenuated after adjustment for age, race and sex (P = 0.33). From our study we concluded that FFAs are elevated in patients with SLE, particularly those with metabolic syndrome. FFAs in patients with SLE are not associated with markers of generalized inflammation but are associated with insulin resistance and markers of endothelial activation.
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  • High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, independent of cardiovascular risk factors and inflammation.
    PloS one (2012)
    Bradham WS, Bian A, Oeser A, Gebretsadik T, Shintani A, Solus J, Estis J, Lu QA, Todd J, Raggi P, Stein CM. High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, independent of cardiovascular risk factors and inflammation. PLoS One. 2012; 7(6):e38930.
    Abstract: We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA).
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  • Changes in cotherapies after initiation of disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis.
    Arthritis care & research (2011)
    Kawai VK, Grijalva CG, Arbogast PG, Curtis JR, Solomon DH, Delzell E, Chen L, Ouellet-Hellstrom R, Herrinton L, Liu L, Mitchel EF Jr, Stein CM, Griffin MR. Changes in cotherapies after initiation of disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011 Oct; 63(10):1415-24.
    Abstract: Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ)and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor α (TNFα) antagonists(new anti-TNF). We compared within-person differences in any use of cotherapies (≥ prescription) between the 6 months before and the 6-12 months after DMARD initiation.Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%,and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95%CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%).Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study.
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  • Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus.
    Lupus (2012)
    Lertnawapan R, Bian A, Rho YH, Raggi P, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM. Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus. Lupus. 2012 Mar; 21(3):279-87.
    Abstract: Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis.
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  • Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis.
    The Journal of rheumatology (2010)
    Chung CP, Oeser A, Raggi P, Sokka T, Pincus T, Solus JF, Linton MF, Fazio S, Stein CM. Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis. J Rheumatol. 2010 Aug 1; 37(8):1633-8.
    Abstract: Patients with rheumatoid arthritis (RA) are at increased risk of atherosclerosis, but routine lipid measurements differ little from those of people without RA. We examined the hypothesis that lipid subclasses determined by nuclear magnetic resonance spectroscopy (NMR) differed in patients with RA compared to controls and are associated with disease activity and the presence of coronary-artery atherosclerosis.
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  • Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis.
    Arthritis and rheumatism (2010)
    Rho YH, Chung CP, Solus JF, Raggi P, Oeser A, Gebretsadik T, Shintani A, Stein CM. Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum. 2010 May; 62(5):1259-64.
    Abstract: The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA.
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Social Interaction and Evaluation in Adolescents with and without Autism

Vanderbilt University Medical Center
  • 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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Increasing HPV Vaccine Utilization among African American Girls through Social Marketing - Phases 1

Vanderbilt University Medical Center
  • 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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Breast Cancer Survivors: Physical Activity, Inflammation, Fatigue, and Distress

The Ohio State University
  • Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2014)
    Kiecolt-Glaser JK, Bennett JM, Andridge R, Peng J, Shapiro CL, Malarkey WB, Emery CF, Layman R, Mrozek EE, Glaser R. Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2014 Apr 1; 32(10):1040-9.
    Abstract: To evaluate yoga's impact on inflammation, mood, and fatigue.
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Cognitive and Neural Correlates of the Picture Superiority Effect in Alzheimer's

Vanderbilt University Medical Center
  • Understanding age-related reductions in visual working memory capacity: examining the stages of change detection.
    Attention, perception & psychophysics (2014)
    Ko PC, Duda B, Hussey E, Mason E, Molitor RJ, Woodman GF, Ally BA. Understanding age-related reductions in visual working memory capacity: examining the stages of change detection. Atten Percept Psychophys. 2014 Oct; 76(7):2015-30.
    Abstract: Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old-new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old-new effects in frontal and occipital areas and a late central-parietal old-new effect, whereas older adults showed a late right-lateralized parietal old-new effect. The younger adults' early old-new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults' behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults.
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  • Pattern separation and pattern completion in Alzheimer's disease: evidence of rapid forgetting in amnestic mild cognitive impairment.
    Hippocampus (2013)
    Ally BA, Hussey EP, Ko PC, Molitor RJ. Pattern separation and pattern completion in Alzheimer's disease: evidence of rapid forgetting in amnestic mild cognitive impairment. Hippocampus. 2013 Dec; 23(12):1246-58.
    Abstract: Over the past four decades, the characterization of memory loss associated with Alzheimer's disease (AD) has been extensively debated. Recent iterations have focused on disordered encoding versus rapid forgetting. To address this issue, we used a behavioral pattern separation task to assess the ability of the hippocampus to create and maintain distinct and orthogonalized visual memory representations in patients with amnestic mild cognitive impairment (aMCI) and mild AD. We specifically used a lag-based continuous recognition paradigm to determine whether patients with aMCI and mild AD fail to encode visual memory representations or whether these patients properly encode representations that are rapidly forgotten. Consistent with the rapid forgetting hypothesis of AD, we found that patients with aMCI demonstrated decreasing pattern separation rates as the lag of interfering objects increased. In contrast, patients with AD demonstrated consistently poor pattern separation rates across three increasingly longer lags. We propose a continuum that reflects underlying hippocampal neuropathology whereby patients with aMCI are able to properly encode information into memory but rapidly lose these memory representations, and patients with AD, who have extensive hippocampal and parahippocampal damage, cannot properly encode information in distinct, orthogonal representations. Our results also revealed that whereas patients with aMCI demonstrated similar behavioral pattern completion rates to healthy older adults, patients with AD showed lower pattern completion rates when we corrected for response bias. Finally, these behavioral pattern separation and pattern completion results are discussed in terms of the dual process model of recognition memory.
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  • Electrophysiological distinctions between recognition memory with and without awareness.
    Neuropsychologia (2013)
    Ko PC, Duda B, Hussey EP, Ally BA. Electrophysiological distinctions between recognition memory with and without awareness. Neuropsychologia. 2013 Mar; 51(4):642-55.
    Abstract: The influence of implicit memory representations on explicit recognition may help to explain cases of accurate recognition decisions made with high uncertainty. During a recognition task, implicit memory may enhance the fluency of a test item, biasing decision processes to endorse it as "old". This model may help explain recognition-without-identification, a remarkable phenomenon in which participants make highly accurate recognition decisions despite the inability to identify the test item. The current study investigated whether recognition-without-identification for pictures elicits a similar pattern of neural activity as other types of accurate recognition decisions made with uncertainty. Further, this study also examined whether recognition-without-identification for pictures could be attained by the use of perceptual and conceptual information from memory. To accomplish this, participants studied pictures and then performed a recognition task under difficult viewing conditions while event-related potentials (ERPs) were recorded. Behavioral results showed that recognition was highly accurate even when test items could not be identified, demonstrating recognition-without-identification. The behavioral performance also indicated that recognition-without-identification was mediated by both perceptual and conceptual information, independently of one another. The ERP results showed dramatically different memory related activity during the early 300 to 500ms epoch for identified items that were studied compared to unidentified items that were studied. Similar to previous work highlighting accurate recognition without retrieval awareness, test items that were not identified, but correctly endorsed as "old," elicited a negative posterior old/new effect (i.e., N300). In contrast, test items that were identified and correctly endorsed as "old," elicited the classic positive frontal old/new effect (i.e., FN400). Importantly, both of these effects were elicited under conditions when participants used perceptual information to make recognition decisions. Conceptual information elicited very different ERPs than perceptual information, showing that the informational wealth of pictures can evoke multiple routes to recognition even without awareness of memory retrieval. These results are discussed within the context of current theories regarding the N300 and the FN400.
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  • Inverse correspondence between hippocampal perfusion and verbal memory performance in older adults.
    Hippocampus (2013)
    Rane S, Ally BA, Hussey E, Wilson T, Thornton-Wells T, Gore JC, Donahue MJ. Inverse correspondence between hippocampal perfusion and verbal memory performance in older adults. Hippocampus. 2013 Mar; 23(3):213-20.
    Abstract: Understanding physiological changes that precede irreversible tissue damage in age-related pathology is central to optimizing treatments that may prevent, or delay, cognitive decline. Cerebral perfusion is a tightly regulated physiological property, coupled to tissue metabolism and function, and abnormal (both elevated and reduced) hippocampal perfusion has been reported in a range of cognitive disorders. However, the size and location of the hippocampus complicates perfusion quantification, as many perfusion techniques acquire data with spatial resolution on the order of or beyond the size of the hippocampus, and are thus suboptimal in this region (especially in the presence of hippocampal atrophy and reduced flow scenarios). Here, the relationship between hippocampal perfusion and atrophy as a function of memory performance was examined in cognitively normal healthy older adults (n = 20; age=67 ± 7 yr) with varying genetic risk for dementia using a custom arterial spin labeling acquisition and analysis procedure. When controlling for hippocampal volume, it was found that hippocampal perfusion correlated inversely (P = 0.04) with memory performance despite absent hippocampal tissue atrophy or white matter disease. The hippocampal flow asymmetry (left hippocampus perfusion-right hippocampus perfusion) was significantly (P = 0.04) increased in APOE-ϵ4 carriers relative to noncarriers. These findings demonstrate that perfusion correlates more strongly than tissue volume with memory performance in cognitively normal older adults, and furthermore that an inverse trend between these two parameters suggests that elevation of neuronal activity, possibly mediated by neuroinflammation and/or excitation/inhibition imbalance, may be closely associated with minor changes in memory performance.
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  • Gist-based conceptual processing of pictures remains intact in patients with amnestic mild cognitive impairment.
    Neuropsychology (2012)
    Deason RG, Hussey EP, Budson AE, Ally BA. Gist-based conceptual processing of pictures remains intact in patients with amnestic mild cognitive impairment. Neuropsychology. 2012 Mar; 26(2):202-8.
    Abstract: The picture superiority effect, better memory for pictures compared to words, has been found in young adults, healthy older adults, and, most recently, in patients with Alzheimer's disease and mild cognitive impairment. Although the picture superiority effect is widely found, there is still debate over what drives this effect. One main question is whether it is enhanced perceptual or conceptual information that leads to the advantage for pictures over words. In this experiment, we examined the picture superiority effect in healthy older adults and patients with amnestic mild cognitive impairment (MCI) to better understand the role of gist-based conceptual processing.
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  • Using mental imagery to improve memory in patients with Alzheimer disease: trouble generating or remembering the mind's eye?
    Alzheimer disease and associated disorders (2012)
    Hussey EP, Smolinsky JG, Piryatinsky I, Budson AE, Ally BA. Using mental imagery to improve memory in patients with Alzheimer disease: trouble generating or remembering the mind's eye? Alzheimer Dis Assoc Disord. 2012 Apr-Jun; 26(2):124-34.
    Abstract: This study was conducted to understand whether patients with mild Alzheimer disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, participants performed 4 imagery tasks with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multisession intervention approach.
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  • Examining the characteristics of episodic memory using event-related potentials in patients with Alzheimer's disease.
    Journal of visualized experiments : JoVE (2011)
    Hussey E, Ally B. Examining the characteristics of episodic memory using event-related potentials in patients with Alzheimer's disease. J Vis Exp. 2011 Aug 30; (54):.
    Abstract: Our laboratory uses event-related EEG potentials (ERPs) to understand and support behavioral investigations of episodic memory in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Whereas behavioral data inform us about the patients' performance, ERPs allow us to record discrete changes in brain activity. Further, ERPs can give us insight into the onset, duration, and interaction of independent cognitive processes associated with memory retrieval. In patient populations, these types of studies are used to examine which aspects of memory are impaired and which remain relatively intact compared to a control population. The methodology for collecting ERP data from a vulnerable patient population while these participants perform a recognition memory task is reviewed. This protocol includes participant preparation, quality assurance, data acquisition, and data analysis. In addition to basic setup and acquisition, we will also demonstrate localization techniques to obtain greater spatial resolution and source localization using high-density (128 channel) electrode arrays.
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Neurobiology of Impulsivity, Risk-Taking and Reward: an fMRI Study

Vanderbilt University Medical Center
  • Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth.
    Developmental cognitive neuroscience (2014)
    Benningfield MM, Blackford JU, Ellsworth ME, Samanez-Larkin GR, Martin PR, Cowan RL, Zald DH. Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth. Dev Cogn Neurosci. 2014 Jan; 7:43-52.
    Abstract: Choices requiring delay of gratification made during adolescence can have significant impact on life trajectory. Willingness to delay gratification can be measured using delay discounting tasks that require a choice between a smaller immediate reward and a larger delayed reward. Individual differences in the subjective value of delayed rewards are associated with risk for development of psychopathology including substance abuse. The neurobiological underpinnings related to these individual differences early in life are not fully understood. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that individual differences in delay discounting behavior in healthy youth are related to differences in responsiveness to potential reward.
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Inflammation and the Heart

Vanderbilt University Medical Center
  • Inflammation and hypertension in rheumatoid arthritis.
    The Journal of rheumatology (2013)
    Manavathongchai S, Bian A, Rho YH, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM. Inflammation and hypertension in rheumatoid arthritis. J Rheumatol. 2013 Nov; 40(11):1806-11.
    Abstract: Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.
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A RANDOMIZED, OPEN-LABEL, CROSS-OVER PILOT STUDY TO INVESTIGATE WHETHER BLACK RASPBERRIES AFFECT POST-PRANDIAL INFLAMMATION IN OVERWEIGHT AND OBESE MALE SUBJECTS

The Ohio State University
  • An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study.
    American journal of therapeutics (2016)
    Sardo CL, Kitzmiller JP, Apseloff G, Harris RB, Roe DJ, Stoner GD, Jacobs ET. An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study. Am J Ther. 2016 Jan-Feb; 23(1):e86-91.
    Abstract: This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL⁻¹·h⁻¹ compared with 42.4 ± 17.9 pg·mL⁻¹·h⁻¹ for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential.
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A New Instrument to Comprehensively Assess Ssedentary Behaviors

Vanderbilt University Medical Center
  • Validation of a previous-day recall measure of active and sedentary behaviors.
    Medicine and science in sports and exercise (2013)
    Matthews CE, Keadle SK, Sampson J, Lyden K, Bowles HR, Moore SC, Libertine A, Freedson PS, Fowke JH. Validation of a previous-day recall measure of active and sedentary behaviors. Med Sci Sports Exerc. 2013 Aug; 45(8):1629-38.
    Abstract: A previous-day recall (PDR) may be a less error-prone alternative to traditional questionnaire-based estimates of physical activity and sedentary behavior (e.g., past year), but the validity of the method is not established. We evaluated the validity of an interviewer administered PDR in adolescents (12-17 yr) and adults (18-71 yr).
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Evaluation of Dermal Myelinated Fibers in Patients with Diabetic Polyneuropathy

Vanderbilt University Medical Center
  • Evaluation of dermal myelinated nerve fibers in diabetes mellitus.
    Journal of the peripheral nervous system : JPNS (2013)
    Peltier AC, Myers MI, Artibee KJ, Hamilton AD, Yan Q, Guo J, Shi Y, Wang L, Li J. Evaluation of dermal myelinated nerve fibers in diabetes mellitus. J Peripher Nerv Syst. 2013 Jun; 18(2):162-7.
    Abstract: Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age-matched healthy controls (age 29-73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.
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MTN 007 - Phase I Randomized Double-Blinded, Placebo-Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (Alabama – Clinical Trials Unit)

The University of Alabama at Birmingham
  • A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007).
    PloS one (2013)
    McGowan I, Hoesley C, Cranston RD, Andrew P, Janocko L, Dai JY, Carballo-Dieguez A, Ayudhya RK, Piper J, Hladik F, Mayer K. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007). PLoS One. 2013; 8(4):e60147.
    Abstract: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel.
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Uremic Modulation of Macrophage Lipid Homeostasis and Inflammatory Functions

Vanderbilt University Medical Center
  • Importance of high-density lipoprotein quality: evidence from chronic kidney disease.
    Current opinion in nephrology and hypertension (2013)
    Kon V, Ikizler TA, Fazio S. Importance of high-density lipoprotein quality: evidence from chronic kidney disease. Curr Opin Nephrol Hypertens. 2013 May; 22(3):259-65.
    Abstract: This review will examine advances in our understanding of the association between high-density lipoprotein (HDL) function and cardiovascular disease (CVD) in patients with chronic kidney disease (CKD).
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  • Dysfunctional high-density lipoprotein in patients on chronic hemodialysis.
    Journal of the American College of Cardiology (2012)
    Yamamoto S, Yancey PG, Ikizler TA, Jerome WG, Kaseda R, Cox B, Bian A, Shintani A, Fogo AB, Linton MF, Fazio S, Kon V. Dysfunctional high-density lipoprotein in patients on chronic hemodialysis. J Am Coll Cardiol. 2012 Dec 11; 60(23):2372-9.
    Abstract: This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD).
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The Effect of a PPAR Alpha Agonist on CYP Monooxygenase Activity in Hymans

Vanderbilt University Medical Center
  • Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.
    Journal of hypertension (2013)
    Gilbert K, Nian H, Yu C, Luther JM, Brown NJ. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension. J Hypertens. 2013 Apr; 31(4):820-9.
    Abstract: Peroxisome proliferator-activated receptor α agonists reduce blood pressure in rodents, but clinical trials provide conflicting data regarding their effects in humans. We tested the hypothesis that the effect of fenofibrate on blood pressure depends on salt sensitivity.
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  • Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans.
    Hypertension (Dallas, Tex. : 1979) (2011)
    Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans. Hypertension. 2011 Jan; 57(1):116-22.
    Abstract: Cytochrome P450-derived epoxyeicosatrienoic acids are potent vasodilators in preclinical models and are hydrolyzed by soluble epoxide hydrolase (EPHX2). Associations between the EPHX2 Lys55Arg and Arg287Gln polymorphisms and cardiovascular disease risk have been reported; however, their impact on vascular function in humans has not been investigated. In 265 volunteers (198 white, 67 black American), forearm blood flow was measured by strain-gauge venous occlusion plethysmography at baseline and in response to bradykinin, methacholine, and sodium nitroprusside. Forearm vascular resistance was calculated as mean arterial pressure/forearm blood flow. In white Americans, Lys55Arg genotype was associated with vasodilator response to bradykinin, such that forearm blood flow was significantly lower (P = 0.043) and forearm vascular resistance was significantly higher (P = 0.013) in Arg55 variant allele carriers compared to wild-type individuals. Significant associations were also observed with methacholine and sodium nitroprusside. In contrast, no relationship was observed in black Americans. In black Americans, Arg287Gln genotype was associated with vasodilator response to bradykinin. Although the difference in forearm blood flow did not reach statistical significance (P = 0.058), forearm vascular resistance was significantly lower (P = 0.037) in Gln287 variant allele carriers compared to wild-type individuals. Significant associations were also observed with methacholine and sodium nitroprusside. In white Americans, Gln287 variant allele carriers did not exhibit significantly higher forearm blood flow (P = 0.128) or lower forearm vascular resistance (P = 0.080). Genetic variation in EPHX2 is associated with forearm vasodilator responses in a bradykinin receptor- and endothelium-independent manner, suggesting an important role for soluble epoxide hydrolase in the regulation of vascular function in humans.
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  • The relationship between peroxisome proliferator-activated receptor-gamma and renin: a human genetics study.
    The Journal of clinical endocrinology and metabolism (2010)
    Underwood PC, Sun B, Williams JS, Pojoga LH, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams GH. The relationship between peroxisome proliferator-activated receptor-gamma and renin: a human genetics study. J Clin Endocrinol Metab. 2010 Sep; 95(9):E75-9.
    Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists often cause volume retention and edema. A relationship between PPARgamma and renin may play a role in this process.
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An 8 week Randomized, Double-Blind, Parallel Group, Multi-Center, Active Controlled Study to Evaluate the Antihypertensive Efficacy and Safety of Aliskiren Administered in Combination with Valsartan versus Valsartan alone in Patients with Stage 2 Systolic Hypertension and Type 2 Diabetes Mellitus

The University of Alabama at Birmingham
  • Randomized study of antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan monotherapy in hypertensive participants with type 2 diabetes mellitus.
    Journal of clinical hypertension (Greenwich, Conn.) (2013)
    Bakris GL, Oparil S, Purkayastha D, Yadao AM, Alessi T, Sowers JR. Randomized study of antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan monotherapy in hypertensive participants with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2013 Feb; 15(2):92-100.
    Abstract: In this double-blind study, 1143 hypertensive participants with type 2 diabetes and stage 1 or 2 chronic kidney disease (CKD) were randomized to receive combination aliskiren/valsartan 150/160 mg or valsartan 160 mg monotherapy for 2 weeks, with force-titration to 300/320 mg and 320 mg, respectively, for another 6 weeks. Ambulatory blood pressure (ABP), the primary outcome, was available for 665 participants. Reductions from baseline to week 8 in 24-hour ABP were -14.1/-8.7 mm Hg with aliskiren/valsartan vs -10.2/-6.3 mm Hg with valsartan (P<.001). Adverse events were reported in 202 participants (35.2%) taking aliskiren/valsartan and 182 participants (32.2%) taking valsartan. No participant had blood urea nitrogen values>40 mg/dL or serum creatinine values>2.0 mg/dL. There were no confirmed cases of serum potassium values≥6.0 mEq/L. Combination aliskiren/valsartan has additive effects on blood pressure reduction and tolerability similar to valsartan in hypertensive/diabetic participants with early-stage (stages 1 and 2) CKD.
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Evaluation of test to detect aromatase inhibitors in the urine - Part C

Columbia University
  • Use of a urine anastrozole assay to determine treatment discontinuation among women with hormone-sensitive breast cancer: a pilot study.
    Journal of oncology practice (2012)
    Clarke Hillyer G, Neugut AI, Crew KD, Kalinsky K, Maurer MA, Rotsides DZ, Danaceau J, Hershman DL. Use of a urine anastrozole assay to determine treatment discontinuation among women with hormone-sensitive breast cancer: a pilot study. J Oncol Pract. 2012 Sep; 8(5):e100-4.
    Abstract: Multiple studies have shown that adherence to adjuvant hormonal therapy in women with breast cancer is suboptimal. Measurements of compliance with self-report, pill counts, and/or pharmacy records are susceptible to bias. We assessed the feasibility of using a urine anastrozole assay as an objective biomarker of nonadherence to anastrozole treatment.
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Group Exercise Training for Functional Improvement after Treatment

Oregon Health & Science University
  • Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial.
    BMC cancer (2012)
    Winters-Stone KM, Li F, Horak F, Luoh SW, Bennett JA, Nail L, Dieckmann N. Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial. BMC Cancer. 2012 Dec 5; 12:577.
    Abstract: Women with cancer are significantly more likely to fall than women without cancer placing them at higher risk of fall-related fractures, other injuries and disability. Currently, no evidence-based fall prevention strategies exist that specifically target female cancer survivors. The purpose of the GET FIT (Group Exercise Training for Functional Improvement after Treatment) trial is to compare the efficacy of two distinct types of exercise, tai chi versus strength training, to prevent falls in women who have completed treatment for cancer. The specific aims of this study are to: 1) Determine and compare the efficacy of both tai chi training and strength training to reduce falls in older female cancer survivors, 2) Determine the mechanism(s) by which tai chi and strength training each reduces falls and, 3) Determine whether or not the benefits of each intervention last after structured training stops.
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"Reproductive Medicine Specimen/Data Repository"

Vanderbilt University Medical Center
  • Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model.
    Fertility and sterility (2013)
    Herington JL, Glore DR, Lucas JA, Osteen KG, Bruner-Tran KL. Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model. Fertil Steril. 2013 Feb; 99(2):543-50.
    Abstract: To examine whether dietary fish oil supplementation reduces development of spontaneous endometriosis-associated adhesions using an established model.
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The Effect of Vitamin D3 Repletion on Small LDL Particle Number in Subjects at Elevated Cardiovascular Risk

The Rockefeller University
  • The short-term effects of vitamin D repletion on cholesterol: a randomized, placebo-controlled trial.
    Arteriosclerosis, thrombosis, and vascular biology (2012)
    Ponda MP, Dowd K, Finkielstein D, Holt PR, Breslow JL. The short-term effects of vitamin D repletion on cholesterol: a randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol. 2012 Oct; 32(10):2510-5.
    Abstract: Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile.
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TrialNet Natural History Study of the Development of Type One Diabetes

Vanderbilt University Medical Center
  • Factors that influence parental attitudes toward enrollment in type 1 diabetes trials.
    PloS one (2012)
    Buscariollo DL, Davidson MA, Black M, Russell WE, Rothman RL, Moore DJ. Factors that influence parental attitudes toward enrollment in type 1 diabetes trials. PLoS One. 2012; 7(8):e44341.
    Abstract: To assess parental attitudes towards type 1 diabetes clinical trials (T1DCTs) and factors that impact willingness to enroll their children with and without diabetes.
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Translating Pharmacogenomic Research to the Clinic: PREDICT Focus Groups Phase 2

Vanderbilt University Medical Center
  • Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project.
    Clinical pharmacology and therapeutics (2012)
    Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH, Delaney JT, Bowton E, Brothers K, Johnson K, Crawford DC, Schildcrout J, Masys DR, Dilks HH, Wilke RA, Clayton EW, Shultz E, Laposata M, McPherson J, Jirjis JN, Roden DM. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012 Jul; 92(1):87-95.
    Abstract: The promise of "personalized medicine" guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision-support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health-care provider, identification of relevant genetic variations for implementation, assay reliability, point-of-care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point-of-care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.
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Evaluating Personalized Information and Choices (EPIC)

University of Washington
  • Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort.
    Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (2012)
    Rosenfeld M, Emerson J, McNamara S, Thompson V, Ramsey BW, Morgan W, Gibson RL, EPIC Study Group.. Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort. J Cyst Fibros. 2012 Sep; 11(5):446-53.
    Abstract: Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to inform prevention strategies and identify high-risk populations.
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  • Baseline characteristics and factors associated with nutritional and pulmonary status at enrollment in the cystic fibrosis EPIC observational cohort.
    Pediatric pulmonology (2010)
    Rosenfeld M, Emerson J, McNamara S, Joubran K, Retsch-Bogart G, Graff GR, Gutierrez HH, Kanga JF, Lahiri T, Noyes B, Ramsey B, Ren CL, Schechter M, Morgan W, Gibson RL, EPIC Study Group Participating Clinical Sites.. Baseline characteristics and factors associated with nutritional and pulmonary status at enrollment in the cystic fibrosis EPIC observational cohort. Pediatr Pulmonol. 2010 Sep; 45(9):934-44.
    Abstract: The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF).
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  • Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'.
    Contemporary clinical trials (2009)
    Treggiari MM, Rosenfeld M, Mayer-Hamblett N, Retsch-Bogart G, Gibson RL, Williams J, Emerson J, Kronmal RA, Ramsey BW, EPIC Study Group.. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials. 2009 May; 30(3):256-68.
    Abstract: The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood.
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SIP5: MANAGING EPILEPSY WELL: SELF -MANAGEMENT INTERVENTION RESEARCH- COORDINATING

Emory University
  • Social support for self-management behaviors among people with epilepsy: a content analysis of the WebEase program.
    Epilepsy & behavior : E&B (2012)
    Walker ER, Bamps Y, Burdett A, Rothkopf J, Diiorio C. Social support for self-management behaviors among people with epilepsy: a content analysis of the WebEase program. Epilepsy Behav. 2012 Mar; 23(3):285-90.
    Abstract: Social support is an important component in managing epilepsy; however little is known about support provided to people with epilepsy. This study examined whom people with epilepsy identify as supportive, and how those individuals support people with epilepsy's self-management efforts. Data come from the WebEase project, an effective online epilepsy self-management program. People with epilepsy who participated in the pilot (n=35) and efficacy trials (n=118) were included. A content analysis was conducted on responses to open-ended questions related to support. The majority of participants provided information about their supporters. The number of support providers ranged from 0 to 6, with about 12% indicating no support. Parents and significant others were most commonly listed as supporters. Support providers mainly offer emotional and instrumental support, reminders and aid for taking medication, and support for self-management strategies. These results could be useful for interventions aimed at bolstering support in order to improve self-management.
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  • Results of a research study evaluating WebEase, an online epilepsy self-management program.
    Epilepsy & behavior : E&B (2011)
    DiIorio C, Bamps Y, Walker ER, Escoffery C. Results of a research study evaluating WebEase, an online epilepsy self-management program. Epilepsy Behav. 2011 Nov; 22(3):469-74.
    Abstract: WebEase (Epilepsy Awareness, Support, and Education) is an online epilepsy self-management program to assist people with taking medication, managing stress, and improving sleep quality. The primary study aims were to determine if those who participated in WebEase demonstrated improvements in medication adherence, perceived stress, and sleep quality. Participants were randomized to a treatment (T) or waitlist control (WCL) group (n=148). At follow-up, participants in the T group reported higher levels of medication adherence than those in the WLC group. Analyses were also conducted comparing those who had completed WebEase modules with those who had not. Those who had completed at least some modules within the WebEase program reported higher levels of self-efficacy and a trend toward significance was observed for the group×time interactions for medication adherence, perceived stress, self-management, and knowledge. The results highlight the usefulness of online tools to support self-management among people with epilepsy.
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The Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome

Vanderbilt University Medical Center
  • Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome.
    Hypertension (Dallas, Tex. : 1979) (2012)
    Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension. 2012 Apr; 59(4):893-8.
    Abstract: Early-generation β-blockers lower blood pressure and reduce cardiovascular morality in coronary artery disease and congestive heart failure but worsen glucose homeostasis and fibrinolytic balance. Nebivolol is a third-generation β-blocker that increases the bioavailability of nitric oxide. We compared the effect of nebivolol (5 mg/d) and the β(1)-selective antagonist metoprolol (100 mg/d) on glucose homeostasis and markers of fibrinolysis in 46 subjects with metabolic syndrome. Subjects underwent a frequently sampled IV glucose tolerance test after 3-week washout and placebo treatment and after randomized treatment with study drug. After 12-week treatment, nebivolol and metoprolol equivalently decreased systolic blood pressure, diastolic blood pressure, and heart rate. Neither drug affected β-cell function, disposition index, or acute insulin response to glucose. Metoprolol significantly decreased the insulin sensitivity index. In contrast, nebivolol did not affect insulin sensitivity, and the decrease in sensitivity was significantly greater after metoprolol than after nebivolol (-1.5±2.5×10(-4)×min(-1) per milliunit per liter versus 0.04±2.19×10(-4)×min(-1) per milliunit per liter after nebivolol; P=0.03). Circulating plasminogen activator inhibitor also increased after treatment with metoprolol (from 9.8±6.8 to 12.3±7.8 ng/mL) but not nebivolol (from 10.8±7.8 to 10.5±6.2 ng/mL; P=0.05 versus metoprolol). Metoprolol, but not nebivolol, increased F(2)-isoprostane concentrations. In summary, treatment with metoprolol decreased insulin sensitivity and increased oxidative stress and the antifibrinolytic plasminogen activator inhibitor 1 in patients with metabolic syndrome, whereas nebivolol lacked detrimental metabolic effects. Large clinical trials are needed to compare effects of nebivolol and the β(1) receptor antagonist metoprolol on clinical outcomes in patients with hypertension and the metabolic syndrome.
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A5267- A Phase I, Safety, Tolerability, and Pharmacokinetic Interaction Study of Single-Dose TMC207 and Efavirenz in Healthy Volunteers

Vanderbilt University Medical Center
  • Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267.
    Journal of acquired immune deficiency syndromes (1999) (2012)
    Dooley KE, Park JG, Swindells S, Allen R, Haas DW, Cramer Y, Aweeka F, Wiggins I, Gupta A, Lizak P, Qasba S, van Heeswijk R, Flexner C, ACTG 5267 Study Team.. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267. J Acquir Immune Defic Syndr. 2012 Apr 15; 59(5):455-62.
    Abstract: Drug-drug interactions complicate management of coinfection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz.
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Research Perceptions Study

Vanderbilt University Medical Center
  • ResearchMatch: a national registry to recruit volunteers for clinical research.
    Academic medicine : journal of the Association of American Medical Colleges (2012)
    Harris PA, Scott KW, Lebo L, Hassan N, Lightner C, Pulley J. ResearchMatch: a national registry to recruit volunteers for clinical research. Acad Med. 2012 Jan; 87(1):66-73.
    Abstract: The authors designed ResearchMatch, a disease-neutral, Web-based recruitment registry to help match individuals who wish to participate in clinical research studies with researchers actively searching for volunteers throughout the United States. In this article, they describe ResearchMatch's stakeholders, workflow model, technical infrastructure, and, for the registry's first 19 months of operation, utilization metrics. Having launched volunteer registration tools in November 2009 and researcher registration tools in March 2010, ResearchMatch had, as of June 2011, registered 15,871 volunteer participants from all 50 states. The registry was created as a collaborative project for institutions in the Clinical and Translational Science Awards (CTSA) consortium. Also as of June 2011, a total of 751 researchers from 61 participating CTSA institutions had registered to use the tool to recruit participants into 540 active studies and trials. ResearchMatch has proven successful in connecting volunteers with researchers, and the authors are currently evaluating regulatory and workflow options to open access to researchers at non-CTSA institutions.
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Healthy Child Weight Through Improved Parent Practices and Environmental Change

University of North Carolina at Chapel Hill
  • Integrating a family-focused approach into child obesity prevention: rationale and design for the My Parenting SOS study randomized control trial.
    BMC public health (2011)
    Ward DS, Vaughn AE, Bangdiwala KI, Campbell M, Jones DJ, Panter AT, Stevens J. Integrating a family-focused approach into child obesity prevention: rationale and design for the My Parenting SOS study randomized control trial. BMC Public Health. 2011 Jun 5; 11:431.
    Abstract: More than 20% of US children ages 2-5 yrs are classified as overweight or obese. Parents greatly influence the behaviors their children adopt, including those which impact weight (e.g., diet and physical activity). Unfortunately, parents often fail to recognize the risk for excess weight gain in young children, and may not be motivated to modify behavior. Research is needed to explore intervention strategies that engage families with young children and motivate parents to adopt behaviors that will foster healthy weight development.
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ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, grants UL1TR000445 and 1U54RR032646-01. The CTSA program is led by the NIH's National Center for Advancing Translational Sciences (NCATS). The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH.

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