Publications by authors named "Jeffrey Martin"

562 Publications

Gritty, hardy, resilient, and socially supported: A replication study.

Disabil Health J 2020 01 5;13(1):100839. Epub 2019 Sep 5.

Divison of Kinesiology, Health and Sport Studies, Wayne State University, Detroit, MI, USA. Electronic address:

Background: The present study adds to the knowledge base in positive psychology and disability sport psychology by replicating and extending the research of Martin, Byrd, Watts, and Dent (2015).

Objectives: In the current study we replicated previous findings by predicting life quality and sport engagement using measures of grit, hardiness, and resilience. We also extended the work of Martin et al. (2015) by examining athlete social support.

Methods: Eighty-seven adult (80 men, 7 women) wheelchair rugby athletes with various disabilities (e.g., amputee) participated in the current study. They completed questionnaires at rugby tournaments or on-line assessing grit, hardiness, resilience, social support and life satisfaction and sport engagement.

Results: Overall, the regression equation predicting life satisfaction was significant, F (4, 81) = 9.67, p < .00, accounting for thirty-two percent of the variance. One variable, resilience, contributed unique meaningful variance as indicated by its significant beta weight (β = 0.46, p < .001). The regression analyses predicting sport engagement was also significant, F (4, 81) = 12.08, p < .001, and predicted 37% of the variance. Grit (β = 0.21, p < .05), social support (β = 0.25, p < .01), resilience (β = 0.23, p < .05), and hardiness (β = 0.27, p < .05) were all significant predictors.

Conclusion: Athletes reporting high levels of resilience reported the highest quality of life. Athletes reporting high levels of grit, resilience, hardiness, and social support were the most engaged in their sport. We also partially replicated the work of Martin et al. (2015).
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http://dx.doi.org/10.1016/j.dhjo.2019.100839DOI Listing
January 2020

Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection.

J Acquir Immune Defic Syndr 2019 10;82(2):211-219

Department of Medicine, University of California, San Francisco, San Francisco, CA.

Background: Reversing or preventing T-cell exhaustion is an important treatment goal in the context of HIV disease; however, the mechanisms that regulate HIV-specific CD8 T-cell exhaustion are incompletely understood. Since mitochondrial mass (MM), mitochondrial membrane potential (MMP), and cellular reactive oxygen species (ROS) content are altered in exhausted CD8 T cells in other settings, we hypothesized that similar lesions may arise in HIV infection.

Methods: We sampled cryopreserved peripheral blood mononuclear cells from HIV-uninfected (n = 10) and HIV-infected participants with varying levels and mechanisms of viral control: viremic (VL > 2000 copies/mL; n = 8) or aviremic (VL < 40 copies/mL) due to antiretroviral therapy (n = 11) or natural control (n = 9). We characterized the MM, MMP, and ROS content of bulk CD8 T cells and MHC class I tetramer+ HIV-specific CD8 T cells by flow cytometry.

Results: We observed higher MM, MMP, and ROS content across bulk effector-memory CD8 T-cell subsets in HIV-infected compared with HIV-uninfected participants. Among HIV-specific CD8 T cells, these features did not vary by the extent or mechanism of viral control but were significantly altered in cells displaying characteristics associated with exhaustion (eg, high PD-1 expression, low CD127 expression, and impaired proliferative capacity).

Conclusions: While we did not find that control of HIV replication in vivo correlates with the CD8 T-cell MM, MMP, or ROS content, we did find that some features of CD8 T-cell exhaustion are associated with alterations in mitochondrial state. Our findings support further studies to probe the relationship between mitochondrial dynamics and CD8 T-cell functionality in HIV infection.
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http://dx.doi.org/10.1097/QAI.0000000000002121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746248PMC
October 2019

Effect of curcumin supplementation on serum expression of select cytokines and chemokines in a female rat model of nonalcoholic steatohepatitis.

BMC Res Notes 2019 Aug 9;12(1):496. Epub 2019 Aug 9.

Department of Cell Biology and Physiology, Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, AL, 36832, USA.

Objective: We recently reported that curcumin supplementation in a metabolically (i.e., Western diet [WD]) and chemically (i.e., CCl) induced female rat model of non-alcoholic steatohepatitis (NASH) was associated with lower liver pathology scores and molecular markers of inflammation. This occurred when curcumin was given during induction of disease (preventative arm; 8-week WD with or without curcumin [8WD + C vs. 8WD]) as well as when given after disease development (treatment arm; 12-week WD with or without curcumin during weeks 9-12 [12WD + C vs. 12WD]). Herein, we sought to extend our findings from that study by determining the effects of curcumin supplementation on cytokine/chemokine expression in serum collected from these same rats.

Results: 24 cytokines/chemokines were assayed. IL-2 (+ 80%) and IL-13 (+ 83%) were greater with curcumin supplementation in the prevention arm. IL-2 (+ 192%), IL-13 (+ 87%), IL-17A (+ 81%) and fractalkine (+ 121%) were higher while RANTES was lower (- 22%) with curcumin supplementation in the treatment arm (p < 0.05 for all). RANTES concentrations also correlated significantly with hepatic pathology scores of inflammation (r = 0.417, p = 0.008). Select serum cytokines/chemokines were affected with curcumin supplementation in this female rat model of NASH. Moreover, curcumin's effect(s) on RANTES and its association with liver disease pathogenesis and progression may warrant further investigation.
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http://dx.doi.org/10.1186/s13104-019-4540-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688243PMC
August 2019

Predicting Happiness in Paralympic Swimming Medalists.

Adapt Phys Activ Q 2019 Jun;36(3):309-324

Griffith University.

The purpose of this study was to predict Paralympian swimmers' happiness as a result of winning 2016 Paralympic medals. Understanding potential antecedents of athletes' happiness has theoretical and practical value. Medal winners (N = 138) had their facial expressions rated for happiness at the race finish. Three predictors were examined: finish place (i.e., first, second, or third), swimmers' expectations for race place, and race time. A multiple-regression analysis predicting happiness was significant, F(3, 98) = 3.66, p < .015, accounting for 10% of the variance. Significant beta weights for race place (β = -0.551) and finishing higher than their 2015 world ranking (β = 0.551) indicated that higher-finishing swimmers were happier than lower-finishing swimmers, and swimmers who finished better than their 2015 ranking were happier than swimmers who finished lower than their ranking. The authors also found partial support for the counterfactual-thinking hypothesis for male swimmers and evidence of gender and country differences in happiness.
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http://dx.doi.org/10.1123/apaq.2018-0140DOI Listing
June 2019

Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda.

Infect Agent Cancer 2019 14;14:14. Epub 2019 May 14.

4Department of Obstetrics and Gynecology, Global Health Institute, Duke University, Durham, North Carolina USA.

Background: New strategies are needed to combat the high incidence of cervical cancer in resource-limited settings such as sub-Saharan Africa. Screening for high-risk human papillomavirus (hrHPV) DNA is sensitive for pre-cancer, but its lack of specificity results in substantial overtreatment in low resource settings where additional testing (e.g., colposcopy) is rarely available. Testing for hrHPV E6/E7 mRNA may enhance specificity, but little is known about its performance characteristics in resource-limited settings.

Methods: In a series of community health fairs in rural Uganda, women aged 25 to 49 years provided self-collected vaginal samples, which were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) E6/E7 mRNA with the Aptima® assay. Positive specimens underwent testing for HPV-16 and 18/45. After excluding pregnant women, all women testing positive for any hrHPV subsequently were offered cervical biopsy to determine pathology.

Results: A total of 1892 women provided a vaginal sample for hrHPV testing during 24 health fairs. The median age was 34 years, HIV prevalence was 10, and 95% had not been previously screened. Prevalence of any hrHPV E6/E7 mRNA was 21% (95% confidence interval (CI): 19 to 23%); the prevalence of HPV-16 was 2.6%, HPV-18/45 1.9%, and HPV 16 and 18/45 were jointly found in 0.1% of the study population. Younger age, pregnancy and HIV-positivity were independently associated with any hrHPV infection. Of the 255 evaluable cervical biopsies, the positive predictive value of detecting any hrHPV E6/E7 mRNA for presence of cervical intraepithelial neoplasia grade 2 or higher ("CIN 2+") was 8.2% (95% CI: 5.1 to 12%). The positive predictive value associated with detection of HPV-16 mRNA (15%) or HPV-18/45 mRNA (15%) was only slightly higher.

Conclusion: Among community-based women in Uganda, the prevalence of any hrHPV E6/E7 mRNA in vaginal samples was high, but the prevalence of the most oncogenic HPV types (16, 18, or 45) was substantially lower. Positive predictive value of hrHPV mRNA-positivity for CIN 2+ was also low, including when restricting to HPV 16/18/45-positivity. The findings emphasize the need to identify more specific screening approaches for cervical cancer.
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http://dx.doi.org/10.1186/s13027-019-0230-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515623PMC
May 2019

Carnitine Is Associated With Atherosclerotic Risk and Myocardial Infarction in HIV -Infected Adults.

J Am Heart Assoc 2019 05;8(9):e011037

3 Division of Cardiology Department of Medicine San Francisco General Hospital University of California, San Francisco San Francisco CA.

Background People living with HIV ( PLWH ) have an increased risk of myocardial infarction ( MI ). Changes in the gut microbiota that occur with chronic HIV infection could play a role in HIV -associated atherosclerosis. Choline, carnitine, betaine, and trimethylamine N-oxide are small molecules that are, in part, metabolized or produced by the gut microbiome. We hypothesized that these metabolites would be associated with carotid artery intima-media thickness and MI in PLWH . Methods and Results Carotid artery intima-media thickness was measured at baseline and at a median interval of 4 years in 162 PLWH from the SCOPE (Study of the Consequences of the Protease Inhibitor Era) cohort in San Francisco, CA . Separately, 105 PLWH (36 cases with type I adjudicated MI and 69 controls without MI ) were selected from the Center for AIDS Research Network of Integrated Clinical Systems, a multicenter clinic-based cohort. Controls were matched by demographics, CD 4 cell count, and duration of viral suppression. In the SCOPE cohort, higher carnitine levels had a significant association with presence of carotid plaque and greater baseline and progression of mean carotid artery intima-media thickness after adjusting for traditional cardiovascular disease risk factors. In the treated and suppressed subgroup, these associations with carnitine remained significant after adjustment for cardiovascular disease risk factors. In the Center for AIDS Research Network of Integrated Clinical Systems cohort, the risk of MI was significantly increased in subjects with carnitine levels in the highest quartile after adjustment for cardiovascular disease risk factors. Conclusions In PLWH , including the treated and suppressed subgroup, carnitine is independently associated with carotid artery intima-media thickness, carotid plaque, and MI in 2 separate cohorts. These results emphasize the potential role of gut microbiota in HIV -associated atherosclerosis and MI , especially in relation to carnitine metabolism.
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http://dx.doi.org/10.1161/JAHA.118.011037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512101PMC
May 2019

High Incidence of Intended Partner Pregnancy Among Men Living With HIV in Rural Uganda: Implications for Safer Conception Services.

J Acquir Immune Defic Syndr 2019 08;81(5):497-507

Division of Infectious Diseases, MGH Global Health, Boston, MA.

Background: Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy in Uganda.

Methods: Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men's sexual and reproductive health annually and repeated at time of reported pregnancy (2011-2015). We measured partner pregnancy incidence overall, by pregnancy intention and by reported partner HIV serostatus. We assessed viral suppression (≤400 copies/mL) during the periconception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy.

Results: Among 189 men, the baseline median age was 39.9 years (interquartile range: 34.7-47.0), years on antiretroviral therapy was 3.9 (interquartile range: 0.0-5.1), and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence = 16.0/100 person-years); 45% with HIV-serodifferent partners. By 3 years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV serostatus (P = 0.75). Sixty-nine percent of pregnancies were intended, 18% wanted but mistimed, and 8% unwanted. Seventy-eight percent of men were virally suppressed before pregnancy report. Men who were younger [adjusted hazard ratio (aHR): 0.94/yr; 95% confidence interval (CI): 0.89 to 0.99], had incomplete primary education (aHR: 2.95; 95% CI: 1.36 to 6.40), and reported fertility desires (aHR: 2.25; 95% CI: 1.04 to 4.85) had higher probability of partner pregnancy.

Conclusions: A high incidence of intended partner pregnancy highlights the need to address men's reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV, and one-quarter of men were not virally suppressed during periconception. Safer conception care provides opportunity to support men's health and reproductive goals, while preventing HIV transmission to women and infants.
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http://dx.doi.org/10.1097/QAI.0000000000002053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625849PMC
August 2019

An integrated transcriptomics and proteomics analysis reveals functional endocytic dysregulation caused by mutations in LRRK2.

Neurobiol Dis 2019 07 5;127:512-526. Epub 2019 Apr 5.

Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. Electronic address:

Background: Mutations in LRRK2 are the most common cause of autosomal dominant Parkinson's disease, and the relevance of LRRK2 to the sporadic form of the disease is becoming ever more apparent. It is therefore essential that studies are conducted to improve our understanding of the cellular role of this protein. Here we use multiple models and techniques to identify the pathways through which LRRK2 mutations may lead to the development of Parkinson's disease.

Methods: A novel integrated transcriptomics and proteomics approach was used to identify pathways that were significantly altered in iPSC-derived dopaminergic neurons carrying the LRRK2-G2019S mutation. Western blotting, immunostaining and functional assays including FM1-43 analysis of synaptic vesicle endocytosis were performed to confirm these findings in iPSC-derived dopaminergic neuronal cultures carrying either the LRRK2-G2019S or the LRRK2-R1441C mutation, and LRRK2 BAC transgenic rats, and post-mortem human brain tissue from LRRK2-G2019S patients.

Results: Our integrated -omics analysis revealed highly significant dysregulation of the endocytic pathway in iPSC-derived dopaminergic neurons carrying the LRRK2-G2019S mutation. Western blot analysis confirmed that key endocytic proteins including endophilin I-III, dynamin-1, and various RAB proteins were downregulated in these cultures and in cultures carrying the LRRK2-R1441C mutation, compared with controls. We also found changes in expression of 25 RAB proteins. Changes in endocytic protein expression led to a functional impairment in clathrin-mediated synaptic vesicle endocytosis. Further to this, we found that the endocytic pathway was also perturbed in striatal tissue of aged LRRK2 BAC transgenic rats overexpressing either the LRRK2 wildtype, LRRK2-R1441C or LRRK2-G2019S transgenes. Finally, we found that clathrin heavy chain and endophilin I-III levels are increased in human post-mortem tissue from LRRK2-G2019S patients compared with controls.

Conclusions: Our study demonstrates extensive alterations across the endocytic pathway associated with LRRK2 mutations in iPSC-derived dopaminergic neurons and BAC transgenic rats, as well as in post-mortem brain tissue from PD patients carrying a LRRK2 mutation. In particular, we find evidence of disrupted clathrin-mediated endocytosis and suggest that LRRK2-mediated PD pathogenesis may arise through dysregulation of this process.
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http://dx.doi.org/10.1016/j.nbd.2019.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597903PMC
July 2019

Effectiveness of Direct-Acting Antiviral Therapy in Patients With Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in Routine Clinical Care: A Multicenter Study.

Open Forum Infect Dis 2019 Apr 23;6(4):ofz100. Epub 2019 Mar 23.

Department of Medicine, University of Washington, Seattle.

Background: Direct-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions.

Methods: The primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values.

Results: Among 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%-97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%-93.6%). Similar results were seen in multiply imputed data sets.

Conclusions: Our study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.
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http://dx.doi.org/10.1093/ofid/ofz100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441587PMC
April 2019

A portable device for nucleic acid quantification powered by sunlight, a flame or electricity.

Nat Biomed Eng 2018 Sep 11;2(9):657-665. Epub 2018 Sep 11.

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.

A decentralized approach to diagnostics can decrease the time to treatment of infectious diseases in resource-limited settings. Yet most modern diagnostic tools require stable electricity and are not portable. Here, we describe a portable device for isothermal nucleic-acid quantification that can operate with power from electricity, sunlight or a flame, and that can store heat from intermittent energy sources, for operation when electrical power is not available or reliable. We deployed the device in two Ugandan health clinics, where it successfully operated through multiple power outages, with equivalent performance when powered via sunlight or electricity. A direct comparison between the portable device and commercial qPCR (quantitative polymerase chain reaction) machines for samples from 71 Ugandan patients (29 of which were tested in Uganda) for the presence of Kaposi's sarcoma-associated herpesvirus DNA showed 94% agreement, with the four discordant samples having the lowest concentration of the herpesvirus DNA. The device's flexibility in power supply provides a needed solution for on-field diagnostics.
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http://dx.doi.org/10.1038/s41551-018-0286-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425734PMC
September 2018

Muscle Damage, Soreness, and Stress During Preseason Training in Collegiate Swimmers.

Clin J Sport Med 2019 Mar 1. Epub 2019 Mar 1.

Exercise Science Program, Oakland University, Rochester, Michigan.

Background: In 2014, 6 collegiate swimmers were hospitalized for symptomatic exertional rhabdomyolysis.

Objective: To serially monitor and assess relationships between skeletal muscle membrane disruption, upper body soreness (UBS) and lower body soreness (LBS), and stress during the first 6 weeks (timepoints) of preseason training in collegiate male and female swimmers.

Design: Prospective observational study.

Setting: College/university.

Participants: Forty swimmers.

Independent Variables: Upper and lower body soreness rating (0-10); testosterone (T), cortisol (C), and T/C ratio.

Main Outcome Measures: Creatine kinase (CK) and myoglobin (over time) versus independent variables.

Results: Weekly training load consisted of ∼87% swimming, ∼5% running, and ∼8% weight training, which increased from 15.8 hours to 20.5 total training hours per week over the first 6 weeks of training. Muscle damage in collegiate swimmers was modest and peaked after the first week of training (week 2) for men (CK = 438 ± 259 U/L; P < 0.0001; r = 0.28; myoglobin = 47 ± 18 ng/mL; P = 0.001; r = 0.22) and women (CK = 446 ± 723 U/L; P < 0.01; r = 0.13; myoglobin = 63 ± 140 ng/mL, not significant) with high variability. Data were presented as peak mean ± SD, significant P-value, and r from repeated-measures analysis of variance. A temporal disconnect was noted between muscle damage and UBS, which peaked at week 5 in both men (5 ± 2; P < 0.0001; r = 0.44) and women (6 ± 2; P < 0.0001; r = 0.57). The serum cortisol level decreased over time, which peaked at week 1 (baseline) in men (15 ± 6 μg/dL; P = 0.0004; r = 0.38) and women (19 ± 10 μg/dL; P < 0.0001; r = 0.49). The testosterone level remained unchanged, which promoted an anabolic hormonal environment that peaked at week 6 (increasing T/C ratio) in men (58 ± 32; P = 0.0003; r = 0.31) and women (4 ± 3; P = 0.04; r = 0.18) despite gradual increases in training and soreness.

Conclusions: Muscle soreness does not parallel muscle membrane disruption. A 1-week "transition" period is required for muscles to adapt to intense/novel training.
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http://dx.doi.org/10.1097/JSM.0000000000000736DOI Listing
March 2019

Knowledge, Attitudes, Self-Efficacy, and Healthy Eating Behavior Among Children: Results From the Building Healthy Communities Trial.

Health Educ Behav 2019 08 21;46(4):602-611. Epub 2019 Feb 21.

1 Wayne State University, Detroit, MI, USA.

. Increased knowledge, attitudes, and beliefs about a topic and behavioral capability and self-efficacy for healthy eating are often a precursor to behavior change. The purpose of this study is to determine the effectiveness of the multicomponent school-based program on children's healthy eating knowledge, attitudes, and self-efficacy for healthy eating, and on their eating habits over time. . Quasi-experimental (4 treatment, 2 comparison) in a metropolitan area using a pretest-posttest method. Participants were 628 fifth-grade youth (377 treatment, 251 comparison) with a mean age of 9.9 years. The Building Healthy Communities (BHC) program is an 8-month school-wide healthy school transformation program and includes six main components. Outcome measures include children's healthy eating knowledge, attitudes, self-efficacy, and behavior. Missing data were imputed, confirmatory factor analysis tested scale factor structure, and path analysis determined a parsimonious path explaining behavior change. . The Student Attitudes and Self-Efficacy (SASE) scale had good measurement model fit. BHC group's healthy eating knowledge and behaviors increased significantly, while SASE remained moderate. For both groups, the students' knowledge and SASE significantly predicted their healthy eating behaviors; however, the intervention group accounted for a greater amount of variance (35% vs. 26%). . The BHC program was effective in improving healthy eating knowledge and behavior among youth, and the relationship between variables did not vary by group. Healthy eating knowledge is a significant predictor of both future knowledge and behavior.
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http://dx.doi.org/10.1177/1090198119826298DOI Listing
August 2019

Overwinter temperature has no effect on problem solving abilities or responses to novelty in Black-capped Chickadees (Poecile atricapillus).

Behav Processes 2019 May 31;162:72-78. Epub 2019 Jan 31.

Department of Biology, University of Western Ontario, London, Ontario, N6A 3K7, Canada; Department of Psychology, University of Western Ontario, London, Ontario, N6A 3K7, Canada; Advanced Facility for Avian Research, University of Western Ontario, London, Ontario, N6A 3K7, Canada. Electronic address:

Birds overwintering at northern latitudes face challenging environments in which refined cognitive and behavioural responses to environmental stimuli could be a benefit. Populations of the same species from different latitudes have been shown to differ in their cognitive and behavioural responses, and these differences have been attributed to local adaptation. However, individuals overwintering at intermediate latitudes experience great breadth and variation in environmental conditions, and thus it is reasonable that these individuals would alter their responses based on current conditions. To determine within-species responses to environmental conditions we sampled birds from a single population at an intermediate latitude and assessed their problem solving abilities and their responses to novelty. We held birds overwinter in one of three experimental temperature regimes and assessed problem solving abilities and responses to novel stimuli in the spring. We found that overwinter temperature had no effect on problem solving ability. We also show that overwinter temperature had no effect on an individual's response to novelty. These findings strengthen the argument that differences in these behaviours seen at the population level are in fact driven by local adaptation, and that current environmental condition may have limited effects on these behaviours.
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http://dx.doi.org/10.1016/j.beproc.2019.01.012DOI Listing
May 2019

Kaposi sarcoma.

Nat Rev Dis Primers 2019 01 31;5(1). Epub 2019 Jan 31.

Leidos Biomedical Research, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; its appearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored.
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http://dx.doi.org/10.1038/s41572-019-0060-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685213PMC
January 2019

OSPREY 3.0: Open-source protein redesign for you, with powerful new features.

J Comput Chem 2018 11 14;39(30):2494-2507. Epub 2018 Oct 14.

Department of Computer Science, Duke University, Durham, North Carolina, 27708.

We present osprey 3.0, a new and greatly improved release of the osprey protein design software. Osprey 3.0 features a convenient new Python interface, which greatly improves its ease of use. It is over two orders of magnitude faster than previous versions of osprey when running the same algorithms on the same hardware. Moreover, osprey 3.0 includes several new algorithms, which introduce substantial speedups as well as improved biophysical modeling. It also includes GPU support, which provides an additional speedup of over an order of magnitude. Like previous versions of osprey, osprey 3.0 offers a unique package of advantages over other design software, including provable design algorithms that account for continuous flexibility during design and model conformational entropy. Finally, we show here empirically that osprey 3.0 accurately predicts the effect of mutations on protein-protein binding. Osprey 3.0 is available at http://www.cs.duke.edu/donaldlab/osprey.php as free and open-source software. © 2018 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcc.25522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391056PMC
November 2018

Contraceptive use following unintended pregnancy among Ugandan women living with HIV.

PLoS One 2018 25;13(10):e0206325. Epub 2018 Oct 25.

Center for Global Health and Division of Infectious Disease, Massachusetts General Hospital, Boston, MA, United States.

Background: Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely achieve their reproductive goals. Family planning services should support WLWH at risk of repeat unintended pregnancies. We examined the relationship between unintended pregnancy and subsequent contraception use among WLWH in Uganda.

Study Design: This was a retrospective analysis of data from a longitudinal cohort of individuals initiating antiretroviral therapy (ART), restricted to women with pregnancy (confirmed via urine β-hcg testing) between 2011-2013. The exposure of interest was intended vs unintended pregnancy, and the outcome was self-report of modern contraceptive use (hormonal methods, intrauterine device, sterilization, and/or consistent condom use) at 12 (range 6-18) months post-partum. A log-binomial model was used to estimate relative risks of modern contraceptive use post-partum based on intent of the index pregnancy, adjusted for age, socioeconomic status, education, relationship and HIV status of pregnancy partner, contraceptive use prior to pregnancy, years since HIV diagnosis, ART regimen, and CD4 cell count.

Results: Among 455 women, 110 women reported 110 incident pregnancies with report on intent. Women had a baseline median age of 29 years, baseline CD4 count 403 cells/mm3, and were living with HIV for 3.8 years. Fifty pregnancies (45%) were reported as unintended and 60 (55%) as intended. Postpartum, 64% of women with unintended and 51% with intended pregnancy reported modern contraception (p = 0.24). In adjusted models, there was no association between pregnancy intent and post-partum contraception. However, contraceptive use prior to the referent pregnancy was positively associated with post-partum contraceptive use (aRR 1.97 (95% CI 1.12-3.48, p = 0.02), while higher baseline CD4 cell count was associated with lower post-partum contraceptive use (aRR 0.95, 95% CI 0.90-0.99, p = 0.02).

Conclusions: Almost half of incident pregnancies among WLWH in this cohort were unintended. Experiencing an unintended pregnancy was not associated with post-partum contraceptive use. Creative strategies to support contraceptive uptake for birth spacing and prevention of unintended pregnancies in the post-partum period are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206325PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201927PMC
April 2019

Parental social support, perceived competence and enjoyment in school physical activity.

J Sport Health Sci 2018 Jul 11;7(3):346-352. Epub 2016 Jan 11.

Division of Kinesiology, Health, and Sport Studies, Wayne State University, Detroit, MI 48202, USA.

Background: Beginning in the elementary school years, there are differences among children on how they perceive their competence in physical activity (PA). Children's competence perceptions may influence their affective reactions to PA. A crucial question is how to motivate children who hold low competence perceptions to enhance their enjoyment and PA involvement. Because parents play critical roles in children's development and socialization, social support from parents can be an important factor to complement teachers' effort to enhance children's enjoyment and PA involvement. In this research we identified the associations among children's beliefs about parental social support, perceived competence, and enjoyment in school PA.

Methods: Three hundred and twenty children (9-11 years old) participated in a two-wave study. At the first wave, children completed questionnaires measuring their beliefs about parental social support, perceived competence, and enjoyment in school PA; they reported their enjoyment again 8 months later at the second wave.

Results: Both concurrent and longitudinal analyses revealed that beliefs about parental social support were important factors associated with children's enjoyment in school PA, especially among girls with low competence perceptions.

Conclusion: Family socialization factors should be taken into consideration. The efficacy of individual and community-level strategies should be included and evaluated when designing effective intervention strategies that enhance children's PA in school.
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http://dx.doi.org/10.1016/j.jshs.2016.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189254PMC
July 2018

Stimulant Use and Viral Suppression in the Era of Universal Antiretroviral Therapy.

J Acquir Immune Defic Syndr 2019 01;80(1):89-93

Department of Medicine, University of California, San Francisco School of Medicine, San Francisco, CA.

Background: HIV-positive persons who use stimulants such as methamphetamine experience difficulties navigating the HIV care continuum that undermine the benefits of antiretroviral therapy (ART). However, few studies have examined the association of stimulant use with viral suppression in the era of universal ART.

Setting: Zuckerberg San Francisco General Hospital.

Methods: HIV-positive persons participating in a clinical cohort study and taking ART completed assessments every 4-6 months. The exposure was the cumulative, time-varying proportion of assessments with any self-reported stimulant use. The time-varying outcome, HIV viral suppression (ie, <200 copies/mL), was measured at assessments or extracted from the clinical record.

Results: In total, 1635 HIV-positive participants on ART contributed 17,610 person-visits over a median of 2.3 [interquartile range (IQR) = 1.0-5.3] years of follow-up. Participants were middle-aged (median = 45.0; IQR = 38.0-52.0), predominantly white (57%), sexual minority men (78%), with a median CD4 T-cell count of 409 (IQR = 225-640) cells/mm at enrollment. Significant increases in odds of viral suppression over time were less pronounced among stimulant users compared with nonusers, particularly before the advent of universal ART. Increasing odds of viral suppression were paralleled by declining stimulant use over time. In the universal ART era, increasing odds of viral suppression were observed at lower levels of stimulant use, but not when participants reported using stimulants at every visit.

Conclusions: Although ART benefits are still not achieved as rapidly in stimulant users, this disparity is not as large in the era of universal ART.
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http://dx.doi.org/10.1097/QAI.0000000000001867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289664PMC
January 2019

HLA-C downregulation by HIV-1 adapts to host HLA genotype.

PLoS Pathog 2018 09 4;14(9):e1007257. Epub 2018 Sep 4.

Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America.

HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in HLA-C downregulation during the first 6 months of infection, but variation between viral quasispecies can be detected in chronic infection. Vpu molecules cloned from plasma of 195 treatment naïve individuals in chronic infection demonstrate that downregulation of HLA-C adapts to host HLA genotype. HLA-C alleles differ in the pressure they exert for downregulation, and individuals with higher levels of HLA-C expression favor greater viral downregulation of HLA-C. Studies of primary and mutant molecules identify 5 residues in the transmembrane region of Vpu, and 4 residues in the transmembrane domain of HLA-C, which determine interactions between Vpu and HLA. The observed adaptation of Vpu-mediated downregulation to host genotype indicates that HLA-C alleles differ in likelihood of mediating a CTL response that is subverted by viral downregulation, and that preservation of HLA-C expression is favored in the absence of these responses. Finding that latent reservoir viruses can downregulate HLA-C could have implications for HIV-1 cure therapy approaches in some individuals.
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http://dx.doi.org/10.1371/journal.ppat.1007257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138419PMC
September 2018

Effect of 1-week betalain-rich beetroot concentrate supplementation on cycling performance and select physiological parameters.

Eur J Appl Physiol 2018 Nov 28;118(11):2465-2476. Epub 2018 Aug 28.

School of Kinesiology, Auburn University, Auburn, AL, USA.

Purpose: Betalains are indole-derived pigments found in beet root, and recent studies suggest that they may exert ergogenic effects. Herein, we examined if supplementation for 7 days with betalain-rich beetroot concentrate (BLN) improved cycling performance or altered hemodynamic and serum analytes prior to, during and following a cycling time trial (TT).

Methods: Twenty-eight trained male cyclists (29 ± 10 years, 77.3 ± 13.3 kg, and 3.03 ± 0.62 W/kg) performed a counterbalanced crossover study whereby BLN (100 mg/day) or placebo (PLA) supplementation occurred over 7 days with a 1-week washout between conditions. On the morning of day seven of each supplementation condition, participants consumed one final serving of BLN or PLA and performed a 30-min cycling TT with concurrent assessment of several physiological variables and blood markers.

Results: BLN supplementation improved average absolute power compared to PLA (231.6 ± 36.2 vs. 225.3 ± 35.8 W, p = 0.050, d = 0.02). Average relative power, distance traveled, blood parameters (e.g., pH, lactate, glucose, NOx) and inflammatory markers (e.g., IL-6, IL-8, IL-10, TNFα) were not significantly different between conditions. BLN supplementation significantly improved exercise efficiency (W/ml/kg/min) in the last 5 min of the TT compared to PLA (p = 0.029, d = 0.45). Brachial artery blood flow in the BLN condition, immediately post-exercise, tended to be greater compared to PLA (p = 0.065, d = 0.32).

Conclusions: We report that 7 days of BLN supplementation modestly improves 30-min TT power output, exercise efficiency as well as post-exercise blood flow without increasing plasma NOx levels or altering blood markers of inflammation, oxidative stress, and/or hematopoiesis.
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http://dx.doi.org/10.1007/s00421-018-3973-1DOI Listing
November 2018

Prevalence and correlates of physical and sexual intimate partner violence among women living with HIV in Uganda.

PLoS One 2018 27;13(8):e0202992. Epub 2018 Aug 27.

Center for Global Health, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.

Background: Intimate partner violence (IPV) is a significant global health problem. Women who experience IPV have increased HIV incidence, reduced antiretroviral adherence, and a lower likelihood of viral load suppression. There is a lack of evidence regarding how to effectively identify and support women living with HIV (WLWH) experiencing IPV, including uncertainty whether universal or targeted screening is most appropriate for lower-resourced settings. We examined physical and sexual IPV prevalence and correlates among WLWH in Uganda to understand the burden of IPV and factors that could help identify women at risk.

Methods: We utilized data from women receiving ART and enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort study between 2011 and 2015. Bloodwork and interviewer-administered questionnaires were completed every 4 months. IPV was assessed annually or with any new pregnancy. Multivariate models assessed independent socio-demographic and clinical factors correlated with IPV, at baseline and follow-up visits.

Results: 455 WLWH were included. Median age was 36 years, 43% were married, and median follow-up was 2.8 years. At baseline 131 women (29%) reported any experience of past or current IPV. In the adjusted models, being married was associated with a higher risk of baseline IPV (ARR 2.33, 95% CI 1.13-4.81) and follow-up IPV (ARR 2.43, 95% CI 1.33-4.45). Older age (ARR 0.96, 95% CI 0.94-0.99) and higher household asset index score (ARR 0.81, 95% CI 0.68-0.96) were associated with lower risk of IPV during follow-up.

Conclusion: There was a high prevalence of physical and sexual IPV amongst WLWH, and many women experienced both types of violence. These findings suggest the need for clinic-based screening for IPV. If universal screening is not feasible, correlates of having experienced IPV can inform targeted approaches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202992PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110509PMC
February 2019

Correction to: Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists.

Amino Acids 2018 10;50(10):1495

School of Kinesiology, Molecular and Applied Sciences Laboratory, Auburn University, 301 Wire Road, Office 286, Auburn, AL, 36849, USA.

For the author R. Mac Thompson, the first name should be R. Mac and the last name should be Thompson. On SpringerLink the name is listed correctly, but on PubMed he is listed as Mac Thompson R.
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http://dx.doi.org/10.1007/s00726-018-2632-5DOI Listing
October 2018

Mast Cell Activation and KSHV Infection in Kaposi Sarcoma.

Clin Cancer Res 2018 10 3;24(20):5085-5097. Epub 2018 Jul 3.

Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York.

Kaposi sarcoma (KS) is a vascular tumor initiated by infection of endothelial cells (ECs) with KS-associated herpesvirus (KSHV). KS is dependent on sustained proinflammatory signals provided by intralesional leukocytes and continued infection of new ECs. However, the sources of these cytokines and infectious virus within lesions are not fully understood. Here, mast cells (MCs) are identified as proinflammatory cells within KS lesions that are permissive for, and activated by, infection with KSHV. Three validated MC lines were used to assess permissivity of MCs to infection with KSHV and to evaluate MCs activation following infection. Biopsies from 31 AIDS-KS cases and 11 AIDS controls were evaluated by IHC for the presence of MCs in KS lesions and assessment of MC activation state and infection with KSHV. Plasma samples from 26 AIDS-KS, 13 classic KS, and 13 healthy adults were evaluated for levels of MC granule contents tryptase and histamine. In culture, MCs supported latent and lytic KSHV infection, and infection-induced MC degranulation. Within KS lesions, MCs were closely associated with spindle cells. Furthermore, MC activation was extensive within patients with KS, reflected by elevated circulating levels of tryptase and a histamine metabolite. One patient with clinical signs of extensive MC activation was treated with antagonists of MC proinflammatory mediators, which resulted in a rapid and durable regression of AIDS-KS lesions. Using complimentary and studies we identify MCs as a potential long-lived reservoir for KSHV and a source of proinflammatory mediators within the KS lesional microenvironment. In addition, we identify MC antagonists as a promising novel therapeutic approach for KS. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191350PMC
October 2018

Curcumin supplementation mitigates NASH development and progression in female Wistar rats.

Physiol Rep 2018 07;6(14):e13789

Department of Biomedical Sciences, Edward Via College of Osteopathic Medicine - Auburn Campus, Auburn, Alabama.

Curcumin, a naturally occurring plant polyphenolic compound, may have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a "western diet" (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC1 injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype. Rats were randomized to four groups (n = 9-12/group) and fed ad libitum: (1) WD for 8-weeks (8WD), (2) WD enriched with curcumin for 8-weeks (8WD+C; 0.2% curcumin, BCM-95, DolCas Biotech) to assess prevention, (3) WD for 12-weeks (12WD), (4) WD for 8-weeks followed by 4-weeks WD+C (12WD+C) to assess treatment. Curcumin prevention (8WD vs. 8WD+C) attenuated (P < 0.05) histological liver inflammation, molecular markers of fibrosis (Col1a1 mRNA) and a serum marker of liver injury (AST). Curcumin treatment (12WD vs. 12WD+C) reduced (P < 0.05) hepatocellular inflammation, steatosis, NAFLD Activity Scores, and serum markers of liver injury (AST, ALP). Moreover, curcumin treatment also increased hepatic pACC/ACC, ApoB100, and SOD1 protein, and decreased hepatic FGF-21 levels; whereas, curcumin prevention increased hepatic glutathione levels. Both curcumin prevention and treatment reduced molecular markers of hepatic fibrosis (Col1a1 mRNA) and inflammation (TNF-α, SPP1 mRNA). Curcumin supplementation beneficially altered the NASH phenotype in female Wistar rats, particularly the reversal of hepatocellular inflammation.
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http://dx.doi.org/10.14814/phy2.13789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046645PMC
July 2018

Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005-2013.

AIDS Patient Care STDS 2018 07;32(7):257-264

1 Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts.

The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-Saharan Africa. We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005-2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazard models to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001-2006, vs. 7.0% in 2007-2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU (p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR.
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http://dx.doi.org/10.1089/apc.2018.0020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034395PMC
July 2018

Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005-2013.

AIDS Patient Care STDS 2018 07;32(7):257-264

1 Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts.

The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-Saharan Africa. We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005-2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazard models to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001-2006, vs. 7.0% in 2007-2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU (p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR.
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http://dx.doi.org/10.1089/apc.2018.0020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034395PMC
July 2018

Continuous Interdomain Orientation Distributions Reveal Components of Binding Thermodynamics.

J Mol Biol 2018 09 18;430(18 Pt B):3412-3426. Epub 2018 Jun 18.

Department of Biochemistry, Duke University, Durham, NC 27710, United States. Electronic address:

The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings, represented as a continuous conformational distribution, and visualized using the disk-on-sphere representation. Using the disk-on-sphere representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions.This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity of Staphylococcus aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing the reorientational components of binding thermodynamics. Such insights allow for the dissection of the dynamic structural components of functionally important intermolecular interactions.
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http://dx.doi.org/10.1016/j.jmb.2018.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115201PMC
September 2018

Red Spinach Extract Increases Ventilatory Threshold during Graded Exercise Testing.

Sports (Basel) 2017 Oct 16;5(4). Epub 2017 Oct 16.

Department of Cell Biology and Physiology, Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36832, USA.

We examined the acute effect of a red spinach extract (RSE) (1000 mg dose; ~90 mg nitrate (NO 3 - )) on performance markers during graded exercise testing (GXT). For this randomized, double-blind, placebo (PBO)-controlled, crossover study, 15 recreationally-active participants (aged 23.1 ± 3.3 years; BMI: 27.2 ± 3.7 kg/m²) reported >2 h post-prandial and performed GXT 65⁻75 min post-RSE or PBO ingestion. Blood samples were collected at baseline (BL), pre-GXT (65⁻75 min post-ingestion; PRE), and immediately post-GXT (POST). GXT commenced with continuous analysis of expired gases. Plasma concentrations of NO 3 - increased PRE (+447 ± 294%; < 0.001) and POST (+378 ± 179%; < 0.001) GXT with RSE, but not with PBO (+3 ± 26%, -8 ± 24%, respectively; > 0.05). No effect on circulating nitrite (NO 2 - ) was observed with RSE (+3.3 ± 7.5%, +7.7 ± 11.8% PRE and POST, respectively; > 0.05) or PBO (-0.5 ± 7.9%, -0.2 ± 8.1% PRE and POST, respectively; > 0.05). When compared to PBO, there was a moderate effect of RSE on plasma NO 2 - at PRE (g = 0.50 [-0.26, 1.24] and POST g = 0.71 [-0.05, 1.48]). During GXT, VO₂ at the ventilatory threshold was significantly higher with RSE compared to PBO (+6.1 ± 7.3%; < 0.05), though time-to-exhaustion (-4.0 ± 7.7%; > 0.05) and maximal aerobic power (i.e., VO₂ peak; -0.8 ± 5.6%; > 0.05) were non-significantly lower with RSE. RSE as a nutritional supplement may elicit an ergogenic response by delaying the ventilatory threshold.
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http://dx.doi.org/10.3390/sports5040080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969023PMC
October 2017

The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study.

Sports (Basel) 2018 Jan 9;6(1). Epub 2018 Jan 9.

School of Kinesiology, Auburn University, Auburn, AL 36849, USA.

Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; = 5) and a KD group ( = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD ( = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% ( = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% ( = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD ( = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO were similar between groups. While our -sizes were limited, these preliminary data suggest that adopting a ketogenic diet causes marked reductions in whole-body adiposity while not impacting performance measures in recreationally-trained CrossFit trainees. Whether decrements in dual-leg muscle mass and vastus lateralis thickness in KD participants were due to fluid shifts remain unresolved, and increased LDL-C in these individuals warrants further investigation.
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http://dx.doi.org/10.3390/sports6010001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969192PMC
January 2018

Unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally.

PeerJ 2018 29;6:e4878. Epub 2018 May 29.

School of Kinesiology, Auburn University, Auburn, AL, United States of America.

Background: We sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow.

Methods: Thirty-two participants completed this two-aim study. In AIM1 ( = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 ( = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m) involved 30-min unilateral EPC ( = 7) or sham ( = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment.

Results: Comparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs;  < 0.05). AIM2: Unilateral EPC treatment was associated with significant increases in whole-leg MST from baseline during (T15: +0.63 ± 0.56 °C in the visible untreated/contralateral leg,  < 0.025) and immediately following treatment (i.e., R0) in both treated (+1.53 ± 0.59 °C) and untreated (+0.60 ± 0.45 °C) legs ( < 0.0125). Across both legs, MST remained elevated with EPC at 30-min post-treatment (+0.60 ± 0.45 °C;  < 0.0167) but not at 60-min post (+0.27 ± 0.46 °C;  = 0.165). Sham treatment was associated with a significant increase in the treated leg immediately post-treatment (+1.12 ± 0.31 °C;  < 0.0167), but not in the untreated leg (-0.27 ± 0.12 °C). MST in neither the treated or untreated leg were increased relative to baseline at R30 or R60 ( > 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly ( < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points.

Discussion: Unilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies.
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http://dx.doi.org/10.7717/peerj.4878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982998PMC
May 2018