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Find video protocols related to scientific articles indexed in Pubmed.
Gut epithelial barrier and systemic inflammation during chronic HIV infection.
AIDS
PUBLISHED: 11-12-2014
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Microbial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4 T-cell recovery has not been well described.
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Persistent HIV-related stigma in rural Uganda during a period of increasing HIV incidence despite treatment expansion.
AIDS
PUBLISHED: 10-01-2014
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Programme implementers have argued that the increasing availability of antiretroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion.
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Identification of genes whose expression is altered by obesity throughout the arterial tree.
Physiol. Genomics
PUBLISHED: 09-30-2014
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We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (?9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications.
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Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
PLoS Pathog.
PUBLISHED: 08-28-2014
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A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r?=?-0.649, p?=?0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p?=?0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r?=?0.733, p?=?0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.
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Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository.
AIDS
PUBLISHED: 08-22-2014
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Cross-sectional HIV incidence surveillance, using assays that distinguish 'recent' from 'nonrecent' infections, has been hampered by inadequate performance and characterization of incidence assays. In this study, the Consortium for the Evaluation and Performance of HIV Incidence Assays presents results of the first independent evaluation of five incidence assays (BED, Limiting Antigen Avidity, Less-sensitive Vitros, Vitros Avidity and BioRad Avidity).
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Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease.
AIDS Res Ther
PUBLISHED: 08-05-2014
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The level (or frequency) of circulating monocyte subpopulations such as classical (CD14(hi)CD16(-)) and non-classical (CD14(dim)CD16(+)) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL?>?10,000 copies/mL], and ART-mediated virologic controllers [VL?
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Empiric deworming and CD4 count recovery in HIV-infected Ugandans initiating antiretroviral therapy.
PLoS Negl Trop Dis
PUBLISHED: 08-01-2014
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There is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.
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Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda.
AIDS Res. Hum. Retroviruses
PUBLISHED: 07-29-2014
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Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n=81 and n=491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002-2004) and main cohort in Mbarara (MBA 2005-2010). TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (?400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p=0.2 and 0.1); time to suppression (log-rank p=0.3 and p=0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.
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Cutting edge: An antibody recognizing ancestral endogenous virus glycoproteins mediates antibody-dependent cellular cytotoxicity on HIV-1-infected cells.
J. Immunol.
PUBLISHED: 07-14-2014
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The failure of antiviral vaccines is often associated with rapid viral escape from specific immune responses. In the past, conserved epitope or algorithmic epitope selections, such as mosaic vaccines, have been designed to diversify immunity and to circumvent potential viral escape. An alternative approach is to identify conserved stable non-HIV-1 self-epitopes present exclusively in HIV-1-infected cells. We showed previously that human endogenous retroviral (HERV) mRNA transcripts and protein are found in cells of HIV-1-infected patients and that HERV-K (HML-2)-specific T cells can eliminate HIV-1-infected cells in vitro. In this article, we demonstrate that a human anti-HERV-K (HML-2) transmembrane protein Ab binds specifically to HIV-1-infected cells and eliminates them through an Ab-dependent cellular cytotoxicity mechanism in vitro. Thus, Abs directed against epitopes other than HIV-1 proteins may have a role in eliminating HIV-1-infected cells and could be targeted in novel vaccine approaches or immunotherapeutic modalities.
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Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa.
AIDS
PUBLISHED: 07-01-2014
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Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.
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Estimation of the Standardized Risk Difference and Ratio in a Competing Risks Framework: Application to Injection Drug Use and Progression to AIDS After Initiation of Antiretroviral Therapy.
Am. J. Epidemiol.
PUBLISHED: 06-27-2014
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There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS.
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Programmed death-1 expression on CD4? and CD8? T cells in treated and untreated HIV disease.
AIDS
PUBLISHED: 05-30-2014
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There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.
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Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers.
AIDS Res. Hum. Retroviruses
PUBLISHED: 05-28-2014
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Galectin-9 (Gal-9) is a ?-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-?, and IL-1?. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r=0.29; p=0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3?pg/ml) and in elite controllers (263.3?pg/ml) compared to age-matched HIV-uninfected controls (54?pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.
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The Factor Structure and Presentation of Depression Among HIV-Positive Adults in Uganda.
AIDS Behav
PUBLISHED: 05-24-2014
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Depression is one of the most prevalent psychiatric comorbidities of HIV and one of the greatest barriers to HIV self-care and adherence. Despite this, little consensus exists on how to best measure depression among people living with HIV/AIDS (PLWHA) in African settings. Measurement of depression among PLWHA may be confounded by somatic symptoms. Some research recommends excluding these items to enhance measurement validity; sensitivity may be lost with this approach. We sought to characterize depression among a cohort (N = 453) of PLWHA initiating antiretroviral therapy in Uganda via factor analysis of a widely used measure of depression, the Hopkins Symptom Checklist (HSCLD). Common factor analysis was performed, associations between HSCLD and the Mental Health subscale of the Medical Outcomes Study HIV (MOS-HIV) estimated, and a Cronbach's alpha calculated to examine validity. Factor analysis yielded two factors: (1) somatic-cognitive symptoms and (2) behavioral disengagement. Persons with more versus less advanced disease (CD4 cell count of ?200 cells/mm(3)) showed no statistically significant differences in depression scores (1.7 vs. 1.7, P ? 0.5). Both factors were significantly associated with the MOS-HIV (P < .01). Factor one was highly reliable (? = .81); factor two had only modest reliability (? = .65). Somatic-cognitive symptoms of depression and disengagement from life's activities appear to be distinct components of depression in this sample. Consideration of somatic items may be valuable in identifying depression in this setting.
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Declining Prevalence of Probable Depression Among Patients Presenting for Antiretroviral Therapy in Rural Uganda: The Role of Early Treatment Initiation.
AIDS Behav
PUBLISHED: 05-03-2014
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Little is known about trends in depression at antiretroviral therapy (ART) initiation among people living with HIV (PLHIV) in low- and middle-income countries. We used data from an ongoing cohort of treatment-naïve PLHIV in rural Uganda to estimate secular trends in depression among PLHIV at ART initiation. We fitted linear regression models with depression symptom severity as the outcome variable and year of cohort entry (2005-2012) as the explanatory variable, adjusting for socio-demographic variables and assessing physical health score, body mass index (BMI), and CD4 count as potential mediators of a secular trend in depression symptom severity. There was a statistically significant negative association between year of entry and depression symptom severity, suggesting a 3.1 % relative decline in the mean depression symptom severity score at ART initiation in each year of study recruitment after the first year. This trend remained statistically significant after inclusion of baseline socio-demographic characteristics to the model and appeared to be driven by improved physical health scores, but not CD4 count or BMI.
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HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
PLoS Pathog.
PUBLISHED: 05-01-2014
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A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
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Peripheral resistance artery blood flow in subjects with abnormal glucose tolerance is improved following enhanced external counterpulsation therapy.
Appl Physiol Nutr Metab
PUBLISHED: 04-29-2014
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Enhanced external counterpulsation (EECP) improves resistance artery function in coronary artery disease patients. However, whether EECP elicits similar effects in persons with abnormal glucose tolerance (AGT) is unknown. Here we provide novel evidence that EECP significantly improves resistance arterial function in the forearm of persons with AGT, whereas the calf only approached significance (P ? 0.10). These improvements were coincident with greater glycemic control, providing further insight into the potential mechanisms of EECP-mediated alterations in glycemia.
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Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection.
J. Infect. Dis.
PUBLISHED: 04-21-2014
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While inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.
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Tobacco use among adults initiating treatment for HIV infection in rural Uganda.
AIDS Behav
PUBLISHED: 03-19-2014
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We conducted a longitudinal study of tobacco use among adults initiating antiretroviral therapy (ART) in Mbarara, Uganda where 11 % of men and 3 % of women use tobacco according to the 2011 Demographic and Health Survey. In a prospective cohort, self-reported tobacco use was assessed before starting ART and reassessed every 3-4 months. Plasma cotinine, a nicotine metabolite, was measured in a subset of adults pre-ART to verify self-report. Among 496 subjects, 50 (10 %) reported current tobacco use (20 % of men, 6 % of women). Most (53 %) adults with elevated cotinine levels (>15 ng/mL) reported no tobacco use. By 6 months after ART initiation, 33 % of tobacco users had quit (95 % CI 20-46 %). By 5 years, 64 % quit (95 % CI 47-77 %). Self-reported tobacco use among rural Ugandans starting ART was twice as common as among the local background population and use may be underreported. ART initiation could be an opportunity for tobacco cessation interventions.
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The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy.
J. Infect. Dis.
PUBLISHED: 02-28-2014
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Human immunodeficiency virus (HIV) infection-induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown.
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Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection.
J. Infect. Dis.
PUBLISHED: 02-28-2014
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Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown.
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Validity of a novel wristband tonometer for measuring central hemodynamics and augmentation index.
Am. J. Hypertens.
PUBLISHED: 02-21-2014
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Central hemodynamic and augmentation indices are independent predictors of cardiovascular events and all-cause mortality that can be estimated noninvasively by pulse wave analysis. The purpose of this study was to assess the reliability and validity of a newly engineered wristband tonometer for acquiring radial artery pressure waveforms.
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Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunction.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 02-13-2014
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Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction (LVD). However, studies have not elucidated the mechanisms of action and overall effects of EECP in patients with LVD. The purpose of the present study was to investigate the effects of EECP on endothelial function in peripheral conduit arteries and exercise capacity (peak Vo2 ) in patients with LVD. Patients with ischaemic LVD (ejection fraction (EF) 34.5 ± 4.2%; n = 9) and patients with symptomatic coronary artery disease (CAD) and preserved LV function (EF 53.5 ± 6.6%; n = 15) were studied before and after 35 sessions (1 h) of EECP. Brachial and femoral artery flow-mediated dilation (bFMD and fFMD, respectively) were evaluated using high-resolution ultrasound. Enhanced external counterpulsation elicited similar significant improvements in the following FMD parameters in the CAD and LVD groups (P ? 0.05 between groups for all): absolute bFMD (+53% and +70%, respectively), relative bFMD (+50% and +74%, respectively), bFMD normalized for shear rate (+70% and +61%, respectively), absolute fFMD (+33% and +21%, respectively) and relative fFMD (+32% and +17%, respectively). In addition, EECP significantly improved plasma levels of nitrate/nitrite (+55% and +28%) and prostacyclin (+50% and +70%), as well as peak Vo2 (+36% and +21%), similarly in both the CAD and LVD groups (P ? 0.05 between groups for all). Despite reduced LV function, EECP therapy significantly improves peripheral vascular function and functional capacity in CAD patients with ischaemic LVD to a similar degree to that seen in CAD patients with preserved LV function.
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Factors associated with delayed hepatitis B viral suppression on tenofovir among patients coinfected with HBV-HIV in the CNICS cohort.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-07-2014
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Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small cohorts of coinfected patients with HBV-HIV. We examined the effect of prior lamivudine (3TC) treatment and other factors on HBV DNA suppression with TDF in a multisite clinical cohort of coinfected patients.
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The dynamic relationship between social support and HIV-related stigma in rural Uganda.
Ann Behav Med
PUBLISHED: 02-07-2014
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Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.
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Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection.
AIDS
PUBLISHED: 01-29-2014
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To examine the relationship between asymmetric dimethylarginine (ADMA) and HIV-associated pulmonary arterial hypertension (PAH).
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Disparities in the quality of HIV care when using US Department of Health and Human Services indicators.
Clin. Infect. Dis.
PUBLISHED: 01-23-2014
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We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ?200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
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Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. I. Impact of obesity.
J. Appl. Physiol.
PUBLISHED: 01-16-2014
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We employed next-generation RNA sequencing (RNA-Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133 downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA [false discovery rate (FDR) < 10%] with an overlap of 93 genes between the arteries. In LETO rats, there were 89 upregulated and 114 downregulated genes in the GFA compared with the SFA. There were 244 upregulated and 275 downregulated genes in OLETF rats (FDR < 10%) in the GFA compared with the SFA, with an overlap of 76 differentially expressed genes common to both LETO and OLETF rats in both the GFA and SFA. A total of 396 transcripts were found to be differentially expressed between LETO and OLETF in aortic endothelial cell-enriched samples. Overall, we found 1) the existence of heterogeneity in the transcriptional profile of the SFA and GFA within healthy LETO rats, 2) that this between-vessel heterogeneity was markedly exacerbated in the hyperphagic, obese OLETF rat, and 3) a greater number of genes whose expression was altered by obesity in the SFA compared with the GFA. Also, results indicate that in OLETF rats the GFA takes on a relatively more proatherogenic phenotype compared with the SFA.
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CD4+ cell count at antiretroviral therapy initiation and economic restoration in rural Uganda.
AIDS
PUBLISHED: 01-11-2014
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To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.
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Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. II. Impact of exercise training in obesity.
J. Appl. Physiol.
PUBLISHED: 01-09-2014
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We employed next-generation RNA sequencing (RNA-Seq) technology to determine the extent to which exercise training alters global gene expression in skeletal muscle feed arteries and aortic endothelial cells of obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Transcriptional profiles of the soleus and gastrocnemius muscle feed arteries (SFA and GFA, respectively) and aortic endothelial cell-enriched samples from rats that underwent an endurance exercise training program (EndEx; n = 12) or a interval sprint training program (IST; n = 12) or remained sedentary (Sed; n = 12) were examined. In response to EndEx, there were 39 upregulated (e.g., MANF) and 20 downregulated (e.g., ALOX15) genes in SFA and 1 upregulated (i.e., Wisp2) and 1 downregulated (i.e., Crem) gene in GFA [false discovery rate (FDR) < 10%]. In response to IST, there were 305 upregulated (e.g., MANF, HSPA12B) and 324 downregulated genes in SFA and 101 upregulated and 66 downregulated genes in GFA, with an overlap of 32 genes between arteries. Furthermore, in aortic endothelial cells, there were 183 upregulated (e.g., eNOS, SOD-3) and 141 downregulated (e.g., ATF3, Clec1b, npy, leptin) genes with EndEx and 71 upregulated and 69 downregulated genes with IST, with an overlap of 35 between exercise programs. Expression of only two genes (Tubb2b and Slc9a3r2) was altered (i.e., increased) by exercise in all three arteries. The finding that both EndEx and IST produced greater transcriptional changes in the SFA compared with the GFA is intriguing when considering the fact that treadmill bouts of exercise are associated with greater relative increases in blood flow to the gastrocnemius muscle compared with the soleus muscle.
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Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection.
Retrovirology
PUBLISHED: 01-07-2014
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Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load.
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HIV antibody characterization as a method to quantify reservoir size during curative interventions.
J. Infect. Dis.
PUBLISHED: 01-02-2014
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Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at high and stable levels in most noncontrollers, elite controllers, and antiretroviral-treated subjects, but a rare subset of controllers had low levels of antibodies against matrix, reverse transcriptase, integrase, and/or protease. Comprehensive HIV antibody profiles may prove useful for monitoring curative interventions.
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Regulatory B cells inhibit cytotoxic T lymphocyte (CTL) activity and elimination of infected CD4 T cells after in vitro reactivation of HIV latent reservoirs.
PLoS ONE
PUBLISHED: 01-01-2014
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During HIV infection, IL-10/IL-10 receptor and programmed death-1 (PD-1)/programmed death-1-ligand (PD-L1) interactions have been implicated in the impairment of cytotoxic T lymphocyte (CTL) activity. Despite antiretroviral therapy (ART), attenuated anti-HIV CTL functions present a major hurdle towards curative measures requiring viral eradication. Therefore, deeper understanding of the mechanisms underlying impaired CTL is crucial before HIV viral eradication is viable. The generation of robust CTL activity necessitates interactions between antigen-presenting cells (APC), CD4+ and CD8+ T cells. We have shown that in vitro, IL-10hiPD-L1hi regulatory B cells (Bregs) directly attenuate HIV-specific CD8+-mediated CTL activity. Bregs also modulate APC and CD4+ T cell function; herein we characterize the Breg compartment in uninfected (HIVNEG), HIV-infected "elite controllers" (HIVEC), ART-treated (HIVART), and viremic (HIVvir), subjects, and in vitro, assess the impact of Bregs on anti-HIV CTL generation and activity after reactivation of HIV latent reservoirs using suberoylanilide hydroxamic acid (SAHA). We find that Bregs from HIVEC and HIVART subjects exhibit comparable IL-10 expression levels significantly higher than HIVNEG subjects, but significantly lower than HIVVIR subjects. Bregs from HIVEC and HIVART subjects exhibit comparable PD-L1 expression, significantly higher than in HIVVIR and HIVNEG subjects. SAHA-treated Breg-depleted PBMC from HIVEC and HIVART subjects, displayed enhanced CD4+ T-cell proliferation, significant upregulation of antigen-presentation molecules, increased frequency of CD107a+ and HIV-specific CD8+ T cells, associated with efficient elimination of infected CD4+ T cells, and reduction in integrated viral DNA. Finally, IL-10-R and PD-1 antibody blockade partially reversed Breg-mediated inhibition of CD4+ T-cell proliferation. Our data suggest that, possibly, via an IL-10 and PD-L1 synergistic mechanism; Bregs likely inhibit APC function and CD4+ T-cell proliferation, leading to anti-HIV CTL attenuation, hindering viral eradication.
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Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging.
PLoS ONE
PUBLISHED: 01-01-2014
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Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase "immunosenesence" of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.
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Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease.
PLoS ONE
PUBLISHED: 01-01-2014
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The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4?CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n?=?42), those with undetectable viral loads on ART ("ART-suppressed", n?=?53), and HIV-uninfected subjects (n?=?22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4?CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7-) T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4?CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-?. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4?CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments.
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Musculoskeletal and Prostate Effects of Combined Testosterone and Finasteride Administration in Older Hypogonadal Men: A Randomized, Controlled Trial.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 12-10-2013
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Testosterone acts directly at androgen receptors and also exerts potent actions following 5?-reduction to dihydrotestosterone (DHT). Finasteride (type II 5?-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men can produce musculoskeletal benefits without prostate enlargement. 60 men aged ?60 years with a serum testosterone concentration of ? 300 ng/dL or bioavailable testosterone ?70 ng/dL received 52 weeks of treatment with testosterone-enanthate (125mg/week) vs. vehicle, paired with finasteride (5mg/day) vs. placebo using a 2x2 factorial design. Over the course of 12 months, testosterone-enanthate increased upper and lower body muscle strength by 8-14% (p=0.015 to <0.001), fat-free mass 4.04 kg (p=0.032), lumbar spine bone mineral density (BMD) 4.19% (p<0.001), and total hip BMD 1.96% (p=0.024), while reducing total body fat -3.87kg (p<0.001) and trunk fat -1.88 kg (p =0.0051). In the first 3 months, testosterone increased hematocrit 4.13% (p<0.001). Co-administration of finasteride did not alter any of these effects. Over 12 months, testosterone also increased prostate volume 11.4 cm(3) (p=0.0051), an effect that was completely prevented by finasteride (p=0.0027). We conclude that a higher-than-replacement testosterone-enanthate, combined with finasteride, significantly increases muscle strength and BMD, and reduces body fat, without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement, but is not required for benefits in musculoskeletal or adipose tissue.
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Comparison of HIV DNA and RNA in gut-associated lymphoid tissue of HIV-infected controllers and noncontrollers.
AIDS
PUBLISHED: 10-26-2013
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HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers.
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Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.
PLoS Pathog.
PUBLISHED: 10-01-2013
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The study of HIV-infected "controllers" who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427).
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Differential Vasomotor Effects of Insulin on Gastrocnemius and Soleus Feed Arteries in the OLETF Rat Model: Role of Endothelin-1.
Exp. Physiol.
PUBLISHED: 08-30-2013
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The vascular actions of insulin are complex as it can stimulate both nitric oxide (NO)-mediated dilation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus (SFA) muscles of 32 wk-old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. SFA dilated more than GFA in LETO at 100 and 1000 ?IU/mL insulin (23% vs 6% and 28% vs. 0%, respectively; P < 0.05 for between-vessel differences). Similarly, in OLETF rats there was significantly greater dilation in SFA than GFA at 10, 100, and 1000 ?IU/mL insulin (28% vs. 3%, 30% vs. 0%, and 34% vs. 0%, respectively; all P < 0.05). In the presence of 3 ?M tezosentan, a non-specific ET-1 receptor blocker, insulin-induced dilation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared to the SFA. Overall, our findings indicate the insulin/ET-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model.
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Measuring the overall genetic component of nevirapine pharmacokinetics and the role of selected polymorphisms: towards addressing the missing heritability in pharmacogenetic phenotypes?
Pharmacogenet. Genomics
PUBLISHED: 08-29-2013
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Nevirapine is an important component of highly active antiretroviral therapy used in the treatment of HIV infection. There is a considerable variation in the pharmacokinetics of nevirapine and this variation can impact the efficacy and toxicity of nevirapine. Although some of this variation can be attributed to environmental factors, the degree to which heritability influences nevirapine pharmacokinetics is unknown. This study aims to estimate how much variation in nevirapine pharmacokinetics is due to genetic factors and to investigate the contribution of selected polymorphisms to this variability.
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Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial.
J. Infect. Dis.
PUBLISHED: 08-23-2013
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The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.
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Human leukocyte antigen B*57 does not fully explain hepatitis C clearance in HIV controllers.
AIDS
PUBLISHED: 08-14-2013
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HIV controllers demonstrate high rates of spontaneous clearance of hepatitis C virus (HCV) infection. The objective of this study was to evaluate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms on HCV clearance in HIV controllers.
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AIDS alters the commensal plasma virome.
J. Virol.
PUBLISHED: 07-31-2013
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We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.
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Self-reported alcohol abstinence associated with ART initiation among HIV-infected persons in rural Uganda.
Drug Alcohol Depend
PUBLISHED: 07-23-2013
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There is limited data on the impact of anti-retroviral treatment (ART) initiation on alcohol consumption. We characterized predictors of abstaining from alcohol among HIV-infected individuals following ART initiation.
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Metformin does not enhance insulin-stimulated vasodilation in skeletal muscle resistance arteries of the OLETF rat.
Microcirculation
PUBLISHED: 07-19-2013
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To test the hypothesis that chronic metformin treatment enhances insulin-induced vasodilation in skeletal muscle resistance arteries and arterioles.
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Benefits and barriers to physical activity for individuals with disabilities: a social-relational model of disability perspective.
Disabil Rehabil
PUBLISHED: 06-19-2013
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To provide a qualitative overview of selected research on physical activity (PA) engagement by people with physical disabilities (1) from a social relational model perspective.
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Exercise training improves endothelial function in young prehypertensives.
Exp. Biol. Med. (Maywood)
PUBLISHED: 06-14-2013
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Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120-139 mmHg; diastolic blood pressure [DBP]=80-89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1? (19% and 22%, respectively; P < 0.05), NO x (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives.
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CD56negCD16+ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection.
Retrovirology
PUBLISHED: 06-12-2013
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A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.
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Real-time adherence monitoring of antiretroviral therapy among hiv-infected adults and children in rural uganda.
AIDS
PUBLISHED: 06-12-2013
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A real-time wireless electronic adherence monitor (EAM) and weekly self-report of missed doses via interactive voice response (IVR) and short message service (SMS) queries were used to measure antiretroviral therapy adherence in 49 adults and 46 children in rural Uganda. Median adherence was 89.5% among adults and 92.8% among children by EAM, and 100% for both adults and children by IVR/SMS self-report. Loss of viral suppression was significantly associated with adherence by EAM (OR 0.58 for each 10% increase), but not IVR/SMS. Wireless EAM creates an exciting opportunity to monitor and potentially intervene with adherence challenges as they are happening.
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Exercise training reduces peripheral arterial stiffness and myocardial oxygen demand in young prehypertensive subjects.
Am. J. Hypertens.
PUBLISHED: 06-04-2013
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Large artery stiffness is a major risk factor for the development of hypertension and cardiovascular disease. Persistent prehypertension accelerates the progression of arterial stiffness.
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Internalized stigma, social distance, and disclosure of HIV seropositivity in rural Uganda.
Ann Behav Med
PUBLISHED: 05-22-2013
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HIV is highly stigmatized, compromising both treatment and prevention in resource-limited settings.
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How does antiretroviral treatment attenuate the stigma of HIV? Evidence from a cohort study in rural Uganda.
AIDS Behav
PUBLISHED: 05-15-2013
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Program implementers and qualitative researchers have described how increasing availability of HIV antiretroviral therapy (ART) is associated with improvements in psychosocial health and internalized stigma. To determine whether, and through what channels, ART reduces internalized stigma, we analyzed data from 262 HIV-infected, treatment-naïve persons in rural Uganda followed from ART initiation over a median of 3.4 years. We fitted Poisson regression models with cluster-correlated robust estimates of variance, specifying internalized stigma as the dependent variable, adjusting for time on treatment as well as socio-demographic, clinical, and psychosocial variables. Over time on treatment, internalized stigma declined steadily, with the largest decline observed during the first 2 years of treatment. This trend remained statistically significant after multivariable adjustment (?(2) = 28.3; P = 0.03), and appeared to be driven by ART-induced improvements in HIV symptom burden, physical and psychological wellbeing, and depression symptom severity.
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The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial.
Blood
PUBLISHED: 04-15-2013
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The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24 (+2.2% vs -0.7%, P = .014), and less of a decline in activated CD4+ T cells (P < .001). The % CD38+HLA-DR+ CD4+ and CD8+ T cells increased nearly twofold in rectal tissue (both P < .001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1?) levels increased 2.4-fold during maraviroc intensification (P < .001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.
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Oral consumption of electrokinetically modified water attenuates muscle damage and improves postexercise recovery.
J. Appl. Physiol.
PUBLISHED: 04-11-2013
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The purpose of this study was to assess the effects of consuming electrokinetically modified water (EMW) on attenuating muscle damage and improving functional recovery following a single bout of isokinetic resistance exercise. Subjects were randomly assigned to an EMW (n = 20) or a placebo control (n = 20) group. Subjects consumed EMW or placebo water daily for 23 days. On day 19 subjects completed an exercise protocol for the biceps brachii to induce muscle damage. The protocol consisted of three sets of 20 repetitions using concentric and eccentric contractions of the elbow flexors. Blood draw and clinical measurements were performed preexercise as well as 24, 48, and 96 h postexercise. Clinical measures included maximal isometric strength, muscle soreness, pain with elbow extension, relaxed elbow angle (RANG), and self-report arm disability. Plasma samples were analyzed to determine concentrations of creatine kinase (CK) and high-sensitivity C-reactive protein (hsCRP). Pain with elbow extension and self-report arm disability were significantly higher in the placebo group compared with the EMW group at 48 h (P < 0.01) and 96 h (P < 0.01) after exercise, while RANG was significantly higher in the EMW group compared with placebo at 48 h (P < 0.01) and 96 h (P < 0.01) after exercise. Similarly, plasma concentrations for hsCRP and CK were significantly lower in the EMW group compared with placebo at 48 h (P < 0.05) and 96 h (P < 0.01) after exercise. Oral consumption of EMW significantly reduced exercise-induced muscle damage and inflammation and improved functional recovery.
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High levels of antiretroviral use and viral suppression among persons in HIV care in the United States, 2010.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-11-2013
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Contemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade.
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Evidence for the reliability and validity of the internalized AIDS-related stigma scale in rural Uganda.
AIDS Behav
PUBLISHED: 04-04-2013
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HIV infection remains highly stigmatized throughout sub-Saharan Africa despite the increasing availability of treatment. HIV-related stigma is commonly described to be highly prevalent in East Africa, but none of these studies have employed validated scales for measurement. We used data from 456 people living with HIV/AIDS in rural Uganda to validate the six-item Internalized AIDS-Related Stigma Scale. The scale demonstrated acceptable internal consistency (Cronbachs alpha = 0.73) and time stability. Exploratory factor analysis indicated the presence of a single factor. Construct validity was supported by observations that the scale was correlated with related constructs such as depression and mental health-related quality of life. The scale was able to discriminate between groups of persons who were different in terms of treatment status and their experience of HIV-related self-blame. Taken together, these findings suggest that the Internalized AIDS-Related Stigma Scale may be a useful tool for socio-behavioral HIV research.
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No association found between traditional healer use and delayed antiretroviral initiation in rural Uganda.
AIDS Behav
PUBLISHED: 04-04-2013
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Traditional healer and/or spiritual counselor (TH/SC) use has been associated with delays in HIV testing. We examined HIV-infected individuals in southwestern Uganda to test the hypothesis that TH/SC use was also associated with lower CD4 counts at antiretroviral therapy (ART) initiation. Approximately 450 individuals initiating ART through an HIV/AIDS clinic at the Mbarara University of Science and Technology (MUST) were recruited to participate. Patients were predominantly female, ranged in age from 18 to 75, and had a median CD4 count of 130. TH/SC use was not associated with lower CD4 cell count, but age and quality-of-life physical health summary score were associated with CD4 cell count at initiation while asset index was negatively associated with CD4 count at ART initiation. These findings suggest that TH/SC use does not delay initiation of ART.
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T cells target APOBEC3 proteins in human immunodeficiency virus type 1-infected humans and simian immunodeficiency virus-infected Indian rhesus macaques.
J. Virol.
PUBLISHED: 03-27-2013
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APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.
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Elevated levels of asymmetric dimethylarginine are associated with lower CD4+ count and higher viral load in HIV-infected individuals.
Atherosclerosis
PUBLISHED: 03-01-2013
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To compare asymmetric dimethylarginine (ADMA) among HIV-infected and uninfected individuals and to evaluate predictors of ADMA in HIV infection.
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Immunosenescence is associated with presence of Kaposis sarcoma in antiretroviral treated HIV infection.
AIDS
PUBLISHED: 02-26-2013
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Some antiretroviral treated HIV-infected patients develop Kaposis sarcoma despite long-term suppression of HIV replication. These Kaposis sarcoma lesions are consistent with Kaposis sarcoma observed in the elderly uninfected population (classical Kaposis sarcoma). We investigated potential mechanisms for this phenomenon, focusing on measures of immune activation and T-cell senescence.
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GPS-measured distance to clinic, but not self-reported transportation factors, are associated with missed HIV clinic visits in rural Uganda.
AIDS
PUBLISHED: 02-26-2013
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Studies of the association between transportation barriers and HIV-related health outcomes have shown both positive and negative effects, possibly because a reliable, validated measure of transportation barriers has not been identified.
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Failure to initiate antiretroviral therapy, loss to follow-up and mortality among HIV-infected patients during the pre-ART period in Uganda.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-23-2013
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Delays and failures in initiation of antiretroviral therapy (ART) among treatment eligible patients may compromise the effectiveness of HIV care in Africa. An accurate understanding, however, of the pace and completeness of ART initiation and mortality during the waiting period is obscured by frequent losses to follow-up.
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Transcriptional response of bathypelagic marine bacterioplankton to the Deepwater Horizon oil spill.
ISME J
PUBLISHED: 02-21-2013
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The Deepwater Horizon blowout released a massive amount of oil and gas into the deep ocean between April and July 2010, stimulating microbial blooms of petroleum-degrading bacteria. To understand the metabolic response of marine microorganisms, we sequenced ? 66 million community transcripts that revealed the identity of metabolically active microbes and their roles in petroleum consumption. Reads were assigned to reference genes from ? 2700 bacterial and archaeal taxa, but most assignments (39%) were to just six genomes representing predominantly methane- and petroleum-degrading Gammaproteobacteria. Specific pathways for the degradation of alkanes, aromatic compounds and methane emerged from the metatranscriptomes, with some transcripts assigned to methane monooxygenases representing highly divergent homologs that may degrade either methane or short alkanes. The microbial community in the plume was less taxonomically and functionally diverse than the unexposed community below the plume; this was due primarily to decreased species evenness resulting from Gammaproteobacteria blooms. Surprisingly, a number of taxa (related to SAR11, Nitrosopumilus and Bacteroides, among others) contributed equal numbers of transcripts per liter in both the unexposed and plume samples, suggesting that some groups were unaffected by the petroleum inputs and blooms of degrader taxa, and may be important for re-establishing the pre-spill microbial community structure.
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Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats.
Metab. Clin. Exp.
PUBLISHED: 01-31-2013
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There is debate as to whether fibronectin type III domain containing 5 (FNDC5) and its protein product irisin are therapeutic targets for obesity-associated maladies. Thus, we sought to examine FNDC5 mRNA within skeletal muscle of obese/diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats versus lean/healthy Long Evans Tokushima Otsuka (LETO) rats. We hypothesized that FNDC5 expression would be greater in obese (OLETF) versus lean (LETO) animals.
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Trends and disparities in antiretroviral therapy initiation and virologic suppression among newly treatment-eligible HIV-infected individuals in North America, 2001-2009.
Clin. Infect. Dis.
PUBLISHED: 01-11-2013
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Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
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Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001-2009.
PLoS ONE
PUBLISHED: 01-01-2013
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U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
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Gag-positive reservoir cells are susceptible to HIV-specific cytotoxic T lymphocyte mediated clearance.
PLoS ONE
PUBLISHED: 01-01-2013
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Resting CD4+T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite controllers (EC) to control virus without therapy due to robust anti-HIV immune responses. Controllers have low levels of integrated HIV DNA and low levels of replication competent virus, suggesting a small reservoir. As our recent data indicates some reservoir cells can produce HIV proteins (termed GPR cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV-expressing resting CD4+T cells could be efficiently targeted and cleared in individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test this we examined if superinfected resting CD4+T cells from EC express HIV Gag without producing infectious virus and the susceptibility of these cells to CTL. We found that resting CD4+T cells expressed HIV Gag and were cleared by autologous CD8+T cells from EC. Importantly, we found the extent of CTL clearance in our in vitro assay correlates with in vivo reservoir size and that a population of Gag expressing resting CD4+T cells exists in vivo in patients well controlled on therapy.
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Disinhibition in risky sexual behavior in men, but not women, during four years of antiretroviral therapy in rural, southwestern Uganda.
PLoS ONE
PUBLISHED: 01-01-2013
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In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.