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Vocal Communication With Canonical Syllables Predicts Later Expressive Language Skills in Preschool-Aged Children With Autism Spectrum Disorder.
McDaniel J, Woynaroski T, Keceli-Kaysili B, Watson LR, Yoder P
(2019) J Speech Lang Hear Res 62: 3826-3833
MeSH Terms: Autism Spectrum Disorder, Child Language, Child, Preschool, Communication, Female, Humans, Language Development Disorders, Longitudinal Studies, Male, Phonetics, Regression Analysis, Speech Production Measurement
Show Abstract · Added March 18, 2020
Purpose We examined associations between vocal communication with canonical syllables and expressive language and then examined 2 potential alternative explanations for such associations. Method Specifically, we tested whether the associations remained when excluding canonical syllables in identifiable words and controlling for the number of communication acts. Participants included 68 preverbal or low verbal children with autism spectrum disorder ( = 35.26 months). Results Vocal communication with canonical syllables and expressive language were concurrently and longitudinally associated with moderate to strong (s = .13-.70) and significant (s < .001) effect sizes. Even when excluding spoken words from the vocal predictor and controlling for the number of communication acts, vocal communication with canonical syllables predicted expressive language. Conclusions The findings provide increased support for measuring vocal communication with canonical syllables and for examining a causal relation between vocal communication with canonical syllables and expressive language in children with ASD who are preverbal or low verbal. In future studies, it may be unnecessary to eliminate identifiable words when measuring vocal communication in this population. Following replication, vocal communication with canonical syllables may be considered when making intervention- planning decisions.
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12 MeSH Terms
The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids.
Bruehl S, Burns JW, Morgan A, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Kingsley PJ, Marnett L, Stone A, Patel S
(2019) Pain 160: 676-687
MeSH Terms: Adult, Analgesics, Opioid, Chronic Pain, Double-Blind Method, Endocannabinoids, Exercise, Female, Humans, Low Back Pain, Male, Middle Aged, Morphine, Naloxone, Opioid Peptides, Pain Measurement, Regression Analysis, Surveys and Questionnaires, Treatment Outcome
Show Abstract · Added April 12, 2019
We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.
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18 MeSH Terms
Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.
Kallianpur AR, Gittleman H, Letendre S, Ellis R, Barnholtz-Sloan JS, Bush WS, Heaton R, Samuels DC, Franklin DR, Rosario-Cookson D, Clifford DB, Collier AC, Gelman B, Marra CM, McArthur JC, McCutchan JA, Morgello S, Grant I, Simpson D, Connor JR, Hulgan T, CHARTER Study Group
(2019) Mol Neurobiol 56: 3808-3818
MeSH Terms: Adult, Antiretroviral Therapy, Highly Active, Biomarkers, Ceruloplasmin, Comorbidity, Female, HIV Infections, Haptoglobins, Humans, Inflammation, Iron, Male, Multivariate Analysis, Neurocognitive Disorders, Regression Analysis, Vascular Endothelial Growth Factor A
Show Abstract · Added December 11, 2019
Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.
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Audiovisual Temporal Processing in Postlingually Deafened Adults with Cochlear Implants.
Butera IM, Stevenson RA, Mangus BD, Woynaroski TG, Gifford RH, Wallace MT
(2018) Sci Rep 8: 11345
MeSH Terms: Acoustic Stimulation, Adult, Aged, Auditory Perception, Cochlear Implants, Deafness, Female, Humans, Judgment, Language, Male, Middle Aged, Regression Analysis, Signal Processing, Computer-Assisted, Speech Perception, Task Performance and Analysis, Time Factors, Visual Perception, Young Adult
Show Abstract · Added March 18, 2020
For many cochlear implant (CI) users, visual cues are vitally important for interpreting the impoverished auditory speech information that an implant conveys. Although the temporal relationship between auditory and visual stimuli is crucial for how this information is integrated, audiovisual temporal processing in CI users is poorly understood. In this study, we tested unisensory (auditory alone, visual alone) and multisensory (audiovisual) temporal processing in postlingually deafened CI users (n = 48) and normal-hearing controls (n = 54) using simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks. We varied the timing onsets between the auditory and visual components of either a syllable/viseme or a simple flash/beep pairing, and participants indicated either which stimulus appeared first (TOJ) or if the pair occurred simultaneously (SJ). Results indicate that temporal binding windows-the interval within which stimuli are likely to be perceptually 'bound'-are not significantly different between groups for either speech or non-speech stimuli. However, the point of subjective simultaneity for speech was less visually leading in CI users, who interestingly, also had improved visual-only TOJ thresholds. Further signal detection analysis suggests that this SJ shift may be due to greater visual bias within the CI group, perhaps reflecting heightened attentional allocation to visual cues.
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Incidence of Nephrotoxicity Among Pediatric Patients Receiving Vancomycin With Either Piperacillin-Tazobactam or Cefepime: A Cohort Study.
Cook KM, Gillon J, Grisso AG, Banerjee R, Jimenez-Truque N, Phillips EJ, Van Driest SL
(2019) J Pediatric Infect Dis Soc 8: 221-227
MeSH Terms: Acute Kidney Injury, Anti-Bacterial Agents, Cefepime, Child, Child, Preschool, Cohort Studies, Combined Modality Therapy, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Multivariate Analysis, Piperacillin, Tazobactam Drug Combination, Regression Analysis, Vancomycin
Show Abstract · Added March 30, 2020
BACKGROUND - Recent studies in adults have found an incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin and piperacillin-tazobactam (TZP) that is greater than that expected with either medication alone. The purpose of this study was to determine whether combination therapy with vancomycin and TZP is associated with an incidence of AKI in pediatric patients higher than that in those on combination therapy with vancomycin and cefepime.
METHODS - We performed a retrospective single-center matched-cohort study of pediatric patients who received vancomycin in combination with TZP or cefepime between January 2015 and June 2016. The patients were matched according to chronic disease, age, sex, and number of concomitant nephrotoxic medications at the time of combination antibiotic therapy. The primary outcome was incidence of AKI. Secondary outcomes included differences between groups in time to AKI, resolution of AKI, and effect of vancomycin trough levels on the incidence of nephrotoxicity. Conditional logistic regression was used to compare categorical and continuous variables between treatment groups. Conditional Poisson regression was used to assess the association between AKI and treatment groups. Stratified log-rank tests and Cox proportional hazards models with shared frailty were used to compare the times to AKI according to treatment group.
RESULTS - Two hundred twenty-eight matched patients were included. AKI developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and TZP groups, respectively (P < .001). Type of combination therapy remained a significant predictor for AKI in multivariate conditional Poisson analysis in which adjustments were made for age, sex, use of concomitant nephrotoxins, and vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03). AKI developed almost 3 times sooner in the TZP group than in the cefepime group (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity analyses in which adjustment was made for antibiotic indication in addition to the aforementioned variables and excluding those with gastrointestinal infection revealed similar results.
CONCLUSION - Among hospitalized children at our institution, combination therapy with vancomycin and TZP was associated with an incidence of AKI higher than that associated with vancomycin and cefepime.
© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Integrating linear optimization with structural modeling to increase HIV neutralization breadth.
Sevy AM, Panda S, Crowe JE, Meiler J, Vorobeychik Y
(2018) PLoS Comput Biol 14: e1005999
MeSH Terms: Algorithms, Amino Acid Motifs, Antibodies, Neutralizing, Computational Biology, Epitopes, HIV Antibodies, HIV Infections, HIV-1, Humans, Linear Models, Machine Learning, Regression Analysis, Software, Support Vector Machine
Show Abstract · Added March 14, 2018
Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
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14 MeSH Terms
Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall.
Emrani S, Libon DJ, Lamar M, Price CC, Jefferson AL, Gifford KA, Hohman TJ, Nation DA, Delano-Wood L, Jak A, Bangen KJ, Bondi MW, Brickman AM, Manly J, Swenson R, Au R, Consortium for Clinical and Epidemiological Neuropsychological Data Analysis (CENDA)
(2018) J Alzheimers Dis 61: 917-928
MeSH Terms: Aged, Aged, 80 and over, Cognitive Dysfunction, Executive Function, Female, Humans, Male, Memory Disorders, Memory, Short-Term, Mental Recall, Neuropsychological Tests, Regression Analysis, Serial Learning
Show Abstract · Added March 16, 2018
BACKGROUND - Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.
OBJECTIVE - The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).
METHODS - Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied.
RESULTS - A 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p < 0.003) serial position 4 (p < 0.002); and lower than both group for serial position 5 (recency; p < 0.002). Mixed/dys MCI patients also produced more transposition errors than both groups (p < 0.010); and more omissions (p < 0.020), and perseverations errors (p < 0.018) than non-MCI patients.
CONCLUSIONS - The attenuation of a recency effect using serial order parameters obtained from the BDT may provide a useful operational definition as well as additional diagnostic information regarding working memory deficits in MCI.
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13 MeSH Terms
Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
Deger SM, Hung AM, Gamboa JL, Siew ED, Ellis CD, Booker C, Sha F, Li H, Bian A, Stewart TG, Zent R, Mitch WE, Abumrad NN, Ikizler TA
(2017) JCI Insight 2:
MeSH Terms: Adult, Animals, Biomarkers, C-Reactive Protein, Cytokines, Disease Models, Animal, Female, Homeostasis, Humans, Inflammation, Integrin beta1, Kinetics, Male, Mice, Mice, Knockout, Middle Aged, Multivariate Analysis, Muscle Proteins, Muscle, Skeletal, Regression Analysis, Renal Dialysis, Renal Insufficiency, Chronic, SKP Cullin F-Box Protein Ligases, Tripartite Motif Proteins, Ubiquitin-Protein Ligases
Show Abstract · Added March 14, 2018
BACKGROUND - Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients.
METHODS - Whole body and skeletal muscle protein turnover were assessed by stable isotope kinetic studies. We incorporated expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin β1 gene KO CKD mice models.
RESULTS - Among 129 patients with mean (± SD) age 47 ± 12 years, 74% were African American, 73% were male, and 22% had diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP) concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically significant associations between hs-CRP and forearm skeletal muscle protein synthesis, degradation, and net forearm skeletal muscle protein balance (P < 0.001 for all). The associations remained statistically significant after adjustment for clinical and demographic confounders, as well as in sensitivity analysis, excluding patients with diabetes mellitus. In attempting to identify potential mechanisms involved in this correlation, we show increased expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue obtained from an animal model of chronic kidney disease.
CONCLUSION - These data suggest that systemic inflammation is a strong and independent determinant of skeletal muscle protein homeostasis in MHD patients, providing rationale for further studies using anticytokine therapies in patients with underlying systemic inflammation.
FUNDING - This study was in part supported by NIH grants R01 DK45604 and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, the Veterans Administration Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant Program, and the FDA grant 000943.
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25 MeSH Terms
R dispersion and sodium imaging in human calf muscle.
Wang P, Zhu H, Kang H, Gore JC
(2017) Magn Reson Imaging 42: 139-143
MeSH Terms: Adult, Aged, Aged, 80 and over, Aging, Extracellular Matrix, Female, Healthy Volunteers, Humans, Leg, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal, Protons, Regression Analysis, Sodium, Water
Show Abstract · Added March 19, 2018
PURPOSE - To evaluate the magnitude of chemical exchange effects and R dispersion in muscle and their relationship to tissue sodium levels with aging.
METHODS - Seven healthy volunteers (aged 24 to 87years, median age 47) underwent MRI to assess tissue sodium levels and water T values at different spin-locking frequencies in calf muscles. T values at each locking field were computed based on a three-parameter mono-exponential model to fit signals obtained at different locking times, and R (=1/T) rates were compared at different locking fields. In particular, the dispersion of R (ΔR=R(0Hz)-R(500Hz)) was examined as a function of subject age. Muscle sodium content was calculated by comparing signal intensities between tissues and reference standards within the same image. The variations of ΔR with age and sodium were analyzed by linear regression.
RESULTS - T values and sodium content both increased with age. R dispersion also increased with age and showed a strong linear correlation (correlation coefficient r=0.98, P=0.000578) with sodium content.
CONCLUSION - ΔR reports on the contribution of labile protons such as hydroxyls which may be associated with macromolecule accumulation in the extracellular matrix (ECM). An increase of sodium signal suggests an enlarged ECM volume fraction and/or an increase in sodium concentration, which occurs during normal aging. The strong correlation between ΔR and sodium is likely the consequence of increased ECM and density of total charged sites within the matrix from molecules such as collagens and proteoglycans. The results from this study show the potential use of R dispersion and sodium imaging in the assessment of pathological changes in muscle such as fibrosis.
Copyright © 2017 Elsevier Inc. All rights reserved.
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18 MeSH Terms
Predicting the Emergence of Community Psychology and Community Development in 91 Countries with Brief Case Studies of Chile and Ghana.
Hanitio F, Perkins DD
(2017) Am J Community Psychol 59: 200-218
MeSH Terms: Chile, Developing Countries, Ghana, Humans, Psychology, Social, Qualitative Research, Regression Analysis, Social Planning
Show Abstract · Added February 8, 2020
Using a mixed-method analysis, we propose and test a framework for predicting the international development of community psychology (CP) and community development (CD) as two examples of applied community-based research (CBR) disciplines aiming to link local knowledge generation with social change. Multiple regressions on an international sample of 91 countries were used to determine the relative influences of preexisting grassroots activism, population size, social and economic development, and civil liberties on estimates of the current strength of CP and CD based on Internet search and review of training courses and programs, published articles and journals, and professional organizations and conferences in these countries. Our results provide support for the proposed model and suggest that grassroots activism positively accounts for the development of CP and CD, above and beyond the influences of the other predictors. Brief qualitative case-study analyses of Chile (high CP, low CD) and Ghana (high CD, low CP) explore the limitations of our quantitative model and the importance of considering other historical, sociopolitical, cultural, and geographic factors for explaining the development of CP, CD, and other applied community studies.
© Society for Community Research and Action 2017.
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