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11.
Victor G. Valcour Serena S. Spudich Napapon Sailasuta Nittaya Phanuphak Sukalaya Lerdlum James L. K. Fletcher Eugene D. M. B. Kroon Linda L. Jagodzinski Isabel E. Allen Collin L. Adams Peeriya Prueksakaew Bonnie M. Slike Joanna M. Hellmuth Jerome H. Kim Jintanat Ananworanich SEARCH /RV Study Group 《PloS one》2015,10(11)
Objective
To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).Design
24-week randomized open-label prospective evaluation.Method
Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.Results
At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.Conclusions
A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. 相似文献12.
13.
Gabriel Tatu-Chitoiu Mircea Cinteza Maria Dorobantu Mariana Udeanu Olivia Manfrini Carmine Pizzi Marius Vintila Dominic D. Ionescu Elvira Craiu Daniel Burghina Raffaele Bugiardini 《CMAJ》2009,180(12):1207-1213
Background
We describe the clinical characteristics, treatments and in-hospital case-fatality rates in an unselected population of patients admitted for acute myocardial infarction.Methods
From January 2000 to June 2007, we tracked consecutive patients who were admitted to 7 tertiary referral and 21 county hospitals in Romania for medical treatment of ST-segment elevation acute myocardial infarction. These patients were enrolled in the Romanian Registry for ST-segment Elevation Myocardial Infarction. For this prospective study, we collected data on demographic characteristics, cardiovascular risk factors, various aspects of treatment for myocardial infarction, and in-hospital death.Results
The 9186 patients in the study group had a mean age of 63.8 years. The median time from onset of symptoms to thrombolysis was 230 (interquartile range 120–510) minutes. Of the 9186 patients, 4986 (54.3%) had hypertension, 1974 (21.5%) had diabetes mellitus, 3545 (38.6%) had lipid disorders and 4653 (50.7%) were smokers. The in-hospital mortality rate was 12.7% (1170 deaths). The study group consisted of 2893 women and 6293 men. The women were older than the men and had higher rates of hypertension and diabetes mellitus but were less likely to be smokers. A smaller proportion of women than men presented within 2 hours after onset of symptoms (23.1% v. 34.4%, p < 0.001). Smaller proportions of women received thrombolytics (40.8% v. 53.5%, p < 0.001), anticoagulants (93.4% v. 95.2%; p = 0.001), antiplatelet agents (88.3% v. 91.2%, p < 0.001) and primary percutaneous coronary interventions (1.5% v. 2.2%, p = 0.030). The risk of in-hospital death was greater for women, even after adjustment for confounders (odds ratio 1.33, 95% confidence interval 1.13–1.56; p < 0.001).Interpretation
The rates of reperfusion therapy for patients with acute myocardial infarction were low, and in-hospital case-fatality rates were high in this study. Excess in-hospital mortality was more pronounced among women.During the past 10 years, the health of people in Eastern Europe and the former Soviet Union has undergone changes very different from the health patterns seen in their Western counterparts. For example, mortality from cardiovascular disease has been decreasing continuously in the United States and many Western European countries, but it has increased or remained unchanged in many of the states of Eastern Europe.1Analysis of this phenomenon has been hindered by insufficient information. The World Health Organization’s MONICA project for monitoring cardiovascular mortality and risk factors considered only 6 Eastern European countries: Russia, Yugoslavia, Poland, Czechoslovakia, Hungary and the former East Germany.2 In geographic terms, Romania is the largest country in southeastern Europe, with a large population and substantial natural resources,3 but in some ways it is a “forgotten country.” Few studies evaluating risks for cardiovascular disease have included Romania. Only 4 trials examining ST-segment elevation myocardial infarction have enrolled patients from Romania,4–6 and the numbers of patients were too few for reliable subgroup analysis.Our aim was to investigate clinical characteristics, treatments and case fatality rates in an unselected population of patients admitted to hospital in Romania for ST-segment elevation myocardial infarction. In a secondary analysis, we analyzed sex differences in relation to treatment and outcome. 相似文献14.
Elicitation of high-frequency cytotoxic T-lymphocyte responses against both dominant and subdominant simian-human immunodeficiency virus epitopes by DNA vaccination of rhesus monkeys 总被引:3,自引:0,他引:3 下载免费PDF全文
Barouch DH Craiu A Santra S Egan MA Schmitz JE Kuroda MJ Fu TM Nam JH Wyatt LS Lifton MA Krivulka GR Nickerson CE Lord CI Moss B Lewis MG Hirsch VM Shiver JW Letvin NL 《Journal of virology》2001,75(5):2462-2467
Increasing evidence suggests that the generation of cytotoxic T-lymphocyte (CTL) responses specific for a diversity of viral epitopes will be needed for an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Here, we determine the frequencies of CTL responses specific for the simian immunodeficiency virus Gag p11C and HIV-1 Env p41A epitopes in simian-human immunodeficiency virus (SHIV)-infected and vaccinated rhesus monkeys. The p11C-specific CTL response was high frequency and dominant and the p41A-specific CTL response was low frequency and subdominant in both SHIV-infected monkeys and in monkeys vaccinated with recombinant modified vaccinia virus Ankara vectors expressing these viral antigens. Interestingly, we found that plasmid DNA vaccination led to high-frequency CTL responses specific for both of these epitopes. These data demonstrate that plasmid DNA may be useful in eliciting a broad CTL response against multiple epitopes. 相似文献
15.
Napapon Sailasuta William Ross Jintanat Ananworanich Thep Chalermchai Victor DeGruttola Sukalaya Lerdlum Mantana Pothisri Edgar Busovaca Silvia Ratto-Kim Linda Jagodzinski Serena Spudich Nelson Michael Jerome H. Kim Victor Valcour for the RV/SEARCH protocol teams 《PloS one》2012,7(11)
Objective
Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART).Methods
Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART.Results
After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months.Interpretation
We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. 相似文献16.
Simon RV Knott Christopher J Viggiani Oscar M Aparicio Simon Tavaré 《BMC bioinformatics》2009,10(1):305
Background
Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult. 相似文献17.
Michael J. Corley Carlo Sacdalan Alina P. S. Pang Nitiya Chomchey Nisakorn Ratnaratorn Victor Valcour Eugene Kroon Kyu S. Cho Andrew C. Belden Donn Colby Merlin Robb Denise Hsu Serena Spudich Robert Paul Sandhya Vasan Lishomwa C. Ndhlovu the SEARCH/RV SEARCH/RV study groups 《PLoS pathogens》2021,17(8)
HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine.Trial Registration: and NCT00782808. NCT00796146相似文献
18.
The tissue and developmental specificities of the three Drosophila isoactins, originally identified in primary myogenic cultures and in the permanent Schneider L-2 cell line, have been investigated. Of these three isoactins (I, II, and III), actins I and II are stable and actin III is unstable. Two-dimensional polyacrylamide gel electrophoretic analyses of total cellular extracts after 1-h [(35)S]methionine pulses were performed on a large variety of embryonic, larval, and adult muscle and nonmuscle tissues. The results suggest that isoactins II and III are generalized cellular actins found in all drosophila cell types. Actin I, on the other hand, is muscle-associated and is found exclusively in supercontractile muscle (such as larval body wall and larval and adult viscera) including primary myogenic cell cultures. Although actin I synthesis is not detectable during very early embryogenesis, it is detectable by 25 h and actin I is a major stable actin in all larval muscle tissues. Actin I is synthesized in reduced amounts relative to the other actins in late third instar larvae but is again a major product of actin synthesis in the adult abdomen. A stable actin species with the same pI as actin III has been identified in the adult thorax and appears to be unique to flight muscle tissue. This new stable form of thoracic actin may be the result of a stabilization of the actin III found in other tissues or may be an entirely separate gene product. 相似文献
19.
This paper considers inference methods for case-control logistic regression in longitudinal setups. The motivation is provided by an analysis of plains bison spatial location as a function of habitat heterogeneity. The sampling is done according to a longitudinal matched case-control design in which, at certain time points, exactly one case, the actual location of an animal, is matched to a number of controls, the alternative locations that could have been reached. We develop inference methods for the conditional logistic regression model in this setup, which can be formulated within a generalized estimating equation (GEE) framework. This permits the use of statistical techniques developed for GEE-based inference, such as robust variance estimators and model selection criteria adapted for non-independent data. The performance of the methods is investigated in a simulation study and illustrated with the bison data analysis. 相似文献