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1.
Int J Pharm ; : 119137, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057889

RESUMO

Niacinamide (NIA) has been widely used in cosmetic and personal care formulations for several skin conditions. Permeation of topical NIA has been confirmed in a number of studies under infinite dose conditions. However, there is limited information in the literature regarding permeation of NIA following application of topical formulations in amounts that reflect the real-life use of such products by consumers. The aim of the present work was therefore to investigate skin delivery of NIA from single solvent systems in porcine skin under finite dose conditions. A secondary aim was to probe the processes underlying the previously reported low recovery of NIA following in vitro permeation and mass balance studies. The solubility and stability of NIA in various single solvent systems was examined. The solvents investigated included Transcutol® P (TC), propylene glycol (PG), 1-2 hexanediol (HEX), 1-2 pentanediol (1-2P), 1-5 pentanediol (1-5P), 1-3 butanediol (1-3B), glycerol (GLY) and dimethyl isosorbide (DMI). Skin permeation and deposition of the molecule was investigated in full thickness porcine skin in vitro finite dose Franz-type diffusion experiments followed by mass balance studies. Stability of NIA for 72 h in the solvents was confirmed. The solubility of NIA in the solvents ranged from 82.9 ± 0.8 to 311.9 ± 4.5 mg/mL. TC delivered the highest percentage permeation of NIA at 24 h, 32.6 ± 12.1 % of the applied dose. Low total recovery of NIA after mass balance studies was observed for some vehicles, with values ranging from 55.2 ± 12.8 % to 106.3 ± 2.3 %. This reflected the formation of a number of NIA degradation by-products in the receptor phase during the permeation studies. Identification of other vehicles for synergistic enhancement of NIA skin delivery will be the subject of future work.

2.
Proc Natl Acad Sci U S A ; 117(3): 1596-1605, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31907313

RESUMO

Hybrid-poplar tree plantations provide a source for biofuel and biomass, but they also increase forest isoprene emissions. The consequences of increased isoprene emissions include higher rates of tropospheric ozone production, increases in the lifetime of methane, and increases in atmospheric aerosol production, all of which affect the global energy budget and/or lead to the degradation of air quality. Using RNA interference (RNAi) to suppress isoprene emission, we show that this trait, which is thought to be required for the tolerance of abiotic stress, is not required for high rates of photosynthesis and woody biomass production in the agroforest plantation environment, even in areas with high levels of climatic stress. Biomass production over 4 y in plantations in Arizona and Oregon was similar among genetic lines that emitted or did not emit significant amounts of isoprene. Lines that had substantially reduced isoprene emission rates also showed decreases in flavonol pigments, which reduce oxidative damage during extremes of abiotic stress, a pattern that would be expected to amplify metabolic dysfunction in the absence of isoprene production in stress-prone climate regimes. However, compensatory increases in the expression of other proteomic components, especially those associated with the production of protective compounds, such as carotenoids and terpenoids, and the fact that most biomass is produced prior to the hottest and driest part of the growing season explain the observed pattern of high biomass production with low isoprene emission. Our results show that it is possible to reduce the deleterious influences of isoprene on the atmosphere, while sustaining woody biomass production in temperate agroforest plantations.

3.
J Neurovirol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933193

RESUMO

The co-occurrence of HIV and alcohol use disorder (AUD) amplifies risk for neural injury and neurocognitive deficits. However, the substantial neurocognitive heterogeneity across HIV+/AUD+ individuals suggests inter-individual differences in vulnerability to the neurotoxicity of comorbid HIV/AUD. Genetic variation in alcohol dehydrogenase (ADH), which metabolizes ethanol, may contribute to inter-individual neurocognitive variability. We evaluated associations between five ADH single-nucleotide polymorphisms (SNPs) and neurocognition in men stratified by HIV and lifetime AUD status. Neurobehavioral assessments were administered to 153 men. Three-way ANOVAs examined the interaction of HIV, AUD, and ADH SNPs on global and domain-specific demographically corrected T scores. Follow-up ANCOVAs adjusted for age, estimated verbal IQ, depression, and remote non-alcohol substance use disorders. HIV/AUD groups differed globally and for verbal fluency, working memory, executive function, and processing speed T scores specifically, with HIV+/AUD+ exhibiting the poorest performance. ADH4 (rs1126671) was associated with large effects on working memory (d = - 1.16, p = .001) and executive function (d = - 0.77, p = .028) selectively in HIV+/AUD+, which remained significant in ANCOVA models. ADH1A (rs3819197) moderated the deleterious effects of HIV+/AUD+ on processing speed such that HIV+/AUD+ related to slower information processing in A allele carriers but not GG homozygotes (ps < 0.03). Preliminary findings suggest genetic variation in the ADH pathway moderates the deleterious neurocognitive effects of comorbid HIV/AUD. Differential metabolism of heavy ethanol exposure may compromise neurocognition under conditions of neurobiological stress, such as in HIV infection. The functional effects on ethanol metabolism of ADH SNPs examined in this study remain poorly understood, warranting further examination of pharmacokinetic mechanisms mediating ADH gene-neurobehavior relationships in HIV.

4.
J Acquir Immune Defic Syndr ; 83(3): 251-259, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31913991

RESUMO

BACKGROUND: Single summary scores, such as the Global Deficit Score, are often used to classify overall performance on neuropsychological batteries. The factor structure of test scores that underlie Global Deficit Score in studies of people living with HIV (PLWH) was assessed to determine whether individual test scores loaded onto a unitary factor to summarize performance. SETTING: Secondary data analysis on baseline data of PLWH from National NeuroAIDS Tissue Consortium and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study. METHOD: Primary analyses included testing model structure and fit of neuropsychological test scores with confirmatory and exploratory factor analyses. Secondary analyses involved receiver operating characteristic curves, and associations with psychosocial and medical variables. RESULTS: Participants with confounds were excluded, leading to 798 (National NeuroAIDS Tissue Consortium) and 1222 (CHARTER) cases. When confirmatory factor analysis models were structured to be consistent with theoretically-based cognitive domains, models did not fit adequately. Per exploratory factor analyses, tests assessing speeded information processing, working memory, and executive functions loaded onto a single factor and explained the most variance in both cohorts. This factor tended to be associated with age, estimated premorbid ability, and aspects of substance use history. Its relation to age, in context of demographically corrected neuropsychological scores, suggested accelerated aging. CONCLUSION: Results indicate that individual neuropsychological tests did not load exactly onto expected domains, suggesting another framework for future analyses of cognitive domains. The possibility of a new index, and its use to assess cognitive impairment in PLWH, is suggested for further diagnostic and prognostic purposes.

5.
New Phytol ; 225(1): 105-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31299099

RESUMO

The response of terrestrial carbon uptake to increasing atmospheric [CO2 ], that is the CO2 fertilization effect (CFE), remains a key area of uncertainty in carbon cycle science. Here we provide a perspective on how satellite observations could be better used to understand and constrain CFE. We then highlight data assimilation (DA) as an effective way to reconcile different satellite datasets and systematically constrain carbon uptake trends in Earth System Models. As a proof-of-concept, we show that joint DA of multiple independent satellite datasets reduced model ensemble error by better constraining unobservable processes and variables, including those directly impacted by CFE. DA of multiple satellite datasets offers a powerful technique that could improve understanding of CFE and enable more accurate forecasts of terrestrial carbon uptake.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31789684

RESUMO

Little is known about the effects of aging-related conditions on health-related quality of life (HRQOL) among people living with HIV (PLWH). The purpose of our study was to examine the independent effects of neurocognitive impairment (NCI) and frailty and the interactive effects with HIV serostatus on HRQOL. Our sample consisted of 121 adults (63 PLWH and 58 HIV-uninfected) participating in the Multi-Dimensional Successful Aging among HIV-Infected Adults study at the University of California, San Diego. HRQOL was measured with the Medical Outcome Study 36-Item Short Form Health Survey scale. We found that frailty was significantly associated with HRQOL (p < .001) in the overall sample, and this effect was significantly stronger for PLWH than HIV-uninfected adults. NCI was not significantly associated with HRQOL in our sample. Frailty may be a particularly important factor in HRQOL for PLWH, highlighting the need for prevention and intervention strategies to mitigate the risks for frailty.

7.
Medicine (Baltimore) ; 98(50): e18232, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852085

RESUMO

Transgender people continue to be at high-risk for HIV acquisition, but little is known about the characteristics of their sexual partners. To address this gap, we examined sociodemographic and sexual characteristics of cisgender men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) reporting transgender sexual partners.A cohort of 392 MSM in southern California in a randomized clinical trial for PrEP adherence were followed from 2013 to 2016. Multivariable generalized estimating equation and logistic models identified characteristics of MSM reporting transgender sexual partners and PrEP adherence.Only 14 (4%) MSM reported having transgender sexual partners. MSM were more likely to report transgender partners if they were African American, had incident chlamydia, reported injection drug-using sexual partners, or received items for sex. Most associations remained significant in the multivariable model: African American (adjusted odds ratio [AOR] 11.20, P = .01), incident chlamydia (AOR 3.71, P = .04), and receiving items for sex (AOR 5.29, P = .04). There were no significant differences in PrEP adherence between MSM reporting transgender partners and their counterpart.MSM who report transgender sexual partners share characteristics associated with individuals with high HIV prevalence. Identifying this group distinct from larger cohorts of MSM could offer new HIV prevention opportunities for this group of MSM and the transgender community.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Prevenção Primária/métodos , Comportamento Sexual , Parceiros Sexuais , Pessoas Transgênero , Adulto , Seguimentos , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Adesão à Medicação , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
8.
J Neurovirol ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858484

RESUMO

Both HIV disease and frailty syndrome are risk factors for neurocognitive impairment. Longitudinal research among individuals of the general population suggests that frailty predicts future cognitive decline; however, there is limited evidence for these longitudinal relationships among people living with HIV (PLWH). The current study evaluated and compared rates of cognitive decline over 2 years among HIV serostatus and frailty status groups. Participants included 50 PLWH and 60 HIV-uninfected (HIV-) participants who were evaluated at baseline and 2-year follow-up visits. Baseline frailty status (non-frail, pre-frail, and frail) was determined using fried frailty phenotype criteria. Neurocognitive functioning was measured using practice-effect corrected scaled scores derived from a comprehensive neuropsychological battery covering seven cognitive domains. Repeated measures analysis was used to estimate rates of global and domain-specific cognitive change from baseline to 2-year follow-up among each of six HIV/frailty status groups. Among PLWH, the pre-frail group demonstrated consistent declines in global cognitive functioning (B = - 0.029, p = 0.034), processing speed (B = - 0.047, p = 0.031), and motor functioning (B = - 0.048, p = 0.038). Among HIV- participants, pre-frail individuals also declined in global cognitive functioning and processing speed (ps ≤ 0.05). HIV- non-frail participants also declined in the cognitive domains of learning, delayed recall, and motor functioning; however, these declines appeared to be driven by relatively higher baseline scores among this group. Notably, 38% of PLWH changed in frailty status from baseline to follow-up, and those with stable pre-frailty demonstrated higher likelihood for cognitive decline; change in depressive symptoms did not relate to change in frailty status. Current findings highlight pre-frailty as an important clinical syndrome that may be predictive of cognitive decline among PLWH. Interventions to prevent or reduce frailty among vulnerable PLWH are needed to maintain optimal cognitive health.

9.
Syst Rev ; 8(1): 287, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771628

RESUMO

BACKGROUND: Inflammation in anterior uveitis is characterised by breakdown of the blood-ocular barrier, which allows leakage of blood constituents of higher molecular weight into the aqueous humour. In routine clinical care, increase in aqueous protein levels can be observed at the slit lamp as 'flare' and the severity can be graded using various clinical grading systems, of which the Standardization of Uveitis Nomenclature (SUN) grading system is most commonly used. Alternative instrument-based technologies are available, which can detect aqueous protein levels in an objective and quantifiable way. This review will identify instruments capable of measuring anterior chamber inflammation in this way, their level of reliability, and how well the measurements correlate with clinical grading and/or actual aqueous protein concentration. METHODS: Standard systematic review methodology will be used to identify, select and extract data from studies that report the use of any instrument-based technology in the assessment of aqueous protein levels. Searches will be conducted through bibliographic databases (MEDLINE, EMBASE and Cochrane Library), clinical trial registries and the grey literature. No restrictions will be placed on language or year of publication. The outcomes of interest are the level of correlation between identified instrument-based test measurements, clinical grading and/or actual aqueous protein concentration, as well as the reliability of each index test identified. Study quality assessment will be based on QUADAS2. Correlation and reliability outcomes will be pooled and meta-analysed if appropriate. DISCUSSION: The assessment of inflammation in anterior chamber protein levels currently relies on crude and subjective clinical examination. The findings of this review will identify non-invasive technologies which show good correlation with actual protein concentration, which could be used in routine clinical practice for objective monitoring of AC inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017084167. Study screening stage has just been completed.

10.
AIDS ; 33(15): 2309-2316, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764096

RESUMO

OBJECTIVE: HIV-associated neurocognitive impairment continues to be prevalent and clinically relevant. We examined the relationship between neurocognition and full plasma HIV RNA suppression among study participants over a 15-year period at a large research program. DESIGN/METHODS: We analyzed the combined prospective studies of the HIV Neurobehavioral Research Program at the University of California at San Diego. Participants were eligible for analysis if on three drug combination antiretroviral therapy with comprehensive neuropsychological testing results. Participants who reported recent nonadherence were excluded. The primary outcome was plasma HIV RNA of 50 copies/ml or less. Generalized estimating equation was used to assess for associations with full virologic suppression taking into account longitudinal visits. RESULTS: There were 1943 participants at baseline, of whom 69.4% had plasma HIV RNA of 50 copies/ml or less. Participants with full suppression were slightly older, less likely to abuse cocaine, and had significantly better executive function. Multivariate analysis with incorporation of longitudinal visits (total = 5555) confirmed current cocaine abuse to be strongly associated with lack of virologic suppression (odds ratio = 0.45, 95% confidence interval = 0.31-0.63). In contrast, increasing age, increasing years of HIV infection, and increasing executive function (odds ratio = 1.18 for T score change of 10, 95% confidence interval = 1.07-1.30) were associated with full virologic suppression. Lack of virologic suppression at baseline was associated with a significant subsequent decline in executive function. CONCLUSION: In a 15-year research cohort of almost 2000 HIV-infected individuals on combination antiretroviral therapy, better executive function was associated with full virologic suppression, possibly as a result rather than a cause.

11.
AIDS ; 33(14): 2157-2166, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31688040

RESUMO

OBJECTIVES: Evidence of accelerated brain aging among HIV-infected adults argues for the increased risk of developing cerebral ß-amyloid (Aß) plaques. We compared the frequency of Aß plaque-bearing cases in our HIV cohort with that in a general cohort reported by Braak et al. We explored posttranslationally modified Aß forms (N3pE, E22P, phospho-Ser8) in plaques and E22P-Aß in the postmortem cerebrospinal fluid (CSF) in the HIV cohort. DESIGN: Clinicopathological study of HIV-infected adults. METHODS: To assess frontal Aß plaque deposition, we conducted immunohistochemistry for generic Aß (4G8) and three modified Aß forms. We determined CSF E22P-Aß levels by ELISA. RESULTS: We found 4G8-Aß plaques in 29% of 279 HIV-infected cases. Within the age range of 31-70 years, the frequency of 4G8-Aß plaque-bearing cases was higher in our HIV cohort (n = 273) compared with the general cohort (n = 1110) overall (29.3 vs. 25.8%) and across four age groups by decade (odds ratio 2.35, P < 0.0001). In HIV-infected cases with (n = 37) and without (n = 12) 4G8-Aß plaques, modified Aß forms occurred in order: N3pE, E22P, and phospho-Ser8. In CSF assays of HIV-infected cases with (n = 27; 17 focal, 10 widespread) and without (n = 11) 4G8-Aß plaques, the median E22P-Aß/Aß40 ratio was higher among cases with widespread plaques than in cases with focal or absent plaques (P = 0.047). CONCLUSION: Our findings suggest HIV-infected adults are at increased risk of developing cerebral Aß plaques. The occurrence of modified Aß forms in order suggests the progression stages of Aß plaque deposition. The potential for E22P-Aß as a CSF biomarker of cerebral Aß plaques should be investigated.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31696212

RESUMO

OBJECTIVE: Neurocognitive performance among older persons, including those living with HIV (people living with HIV [PLWH]), exhibits significant heterogeneity, suggesting subpopulations with differing profiles of neurocognitive impairment (NCI). Metabolic factors are associated with NCI, but their relationships to cluster-derived NCI profiles are unknown. METHOD: Participants (144 PLWH and 102 HIV uninfected) aged 50+ years completed a neuropsychological battery assessing seven cognitive domains. Latent class analysis (LCA) identified NCI profiles separately by HIV serostatus and in a combined sample. Obtained classes were examined against the Montreal Cognitive Assessment (MoCA) and diagnoses of HIV-associated neurocognitive disorders (HAND). Multinomial regression identified metabolic predictors of classification. RESULTS: LCA identified three latent classes in each participant sample: Class1Multidomain NCI (high probability of impairment across multiple domains), Class 2Learning & Recall NCI (high probability of impairment in learning and recall), and Class 3NC Unimpaired (low probability of NCI across all domains). Severity of NCI implied by classes corresponded with MoCA scores and HAND diagnoses. In analyses on the combined sample, compared to HIV-uninfected individuals, PLWH were more likely to be in Class1Multidomain NCI. Among PLWH, those with dyslipidemia and hypertension had greater odds of classification in Class 1Multidomain NCI while those with central obesity had higher odds of classification in Class 2Learning & Recall NCI; metabolic syndrome approached significance as a differential predictor. Regardless of HIV status, individuals with diabetes were more likely to be in Class 1Multidomain NCI. CONCLUSIONS: Metabolic risk factors confer heightened risk of NCI in HIV infection. Interventions to reduce metabolic risk may improve neurocognitive outcomes among PLWH.

13.
Arch Sex Behav ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591666

RESUMO

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM.

14.
Int J Pharm X ; 1: 100025, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31517290

RESUMO

l-ascorbic acid (AA), commonly known as vitamin C, has been widely used in topical formulations for many years as an antioxidant and anti-aging ingredient. However, the physicochemical properties of AA are not optimal for skin uptake and the molecule is also unstable, readily undergoing oxidation on exposure to air. The compound 3-o-ethyl-l-ascorbic acid (EA) has been developed as a stable vitamin C derivative and has been used in topical products. The aims of this work were to conduct a comprehensive characterisation of physicochemical properties of EA as well as to investigate the influence of various neat solvents on EA skin delivery. Nuclear magnetic resonance (NMR), mass spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterise the molecule. The pKa of the compound and the partition coefficient logP(o/w) were experimentally determined. A new HPLC method for analysis of the molecule was also developed and validated. A number of solvents for topical preparations were selected based on their wide use as excipients in topical formulations, their potential to act as skin penetration enhancers and their favourable safety profiles. The solubility and stability of EA was examined. Skin permeation of the molecule in full thickness porcine skin in vitro was investigated using Franz-type diffusion cells. The melting point, log P(o/w) value and pKa value of EA were determined to be 114.39 ±â€¯0.5 °C, -1.07 ±â€¯0.03 and 7.72 ±â€¯0.01 respectively. Skin penetration of EA was evident for the following vehicles 1,2 hexanediol (HEX), glycerol (GLY), propylene glycol (PG), 1,2 pentanediol (1-2P), isopropyl alcohol (IPA), propylene glycol monolaurate (PGML) and propylene glycol monocaprylate (PGMC). Skin uptake but no permeation through the skin was observed for Transcutol® (TC) and dipropylene glycol (DiPG), while no penetration was observed for the solvents 1,5 pentanediol (1-5P) and tripropylene glycol (TriPG). The findings of the permeation experiments confirm the potential of simple formulations to deliver EA to the skin. Studies are ongoing to identify complex vehicles for synergistic enhancement of EA skin penetration. To our knowledge this is the first study to conduct a comprehensive characterization of EA and examine its skin uptake and permeation properties in porcine skin.

15.
Ocul Immunol Inflamm ; : 1-12, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418609

RESUMO

Purpose: New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods: Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results: From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66-0.87 and 0.06-0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73-0.97) than in the inferior AC (0.06-0.56). Conclusion: AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity.

16.
Sci Rep ; 9(1): 12595, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467358

RESUMO

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7-54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of "perceptual noise." This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population.

17.
AIDS Res Hum Retroviruses ; 35(11-12): 985-998, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31373216

RESUMO

In the era of effective antiretroviral therapy, the number of older people with HIV (PWH) is increasing, and those aging with HIV are experiencing an increasing burden of age-associated comorbidities. Life expectancy among older PWH is approaching that of demographically comparable HIV-uninfected (HIV-) adults. With this changing demographic of PWH come new challenges for researchers and clinicians in how to identify, address, and manage the complex interplay of treated HIV infection and aging-associated factors. In response to these challenges, the annual International Workshop on HIV and Aging was initiated in 2009 as a multidisciplinary platform for scientific discourse on the research and clinical complications arising from the aging population of PWH. The multidisciplinary nature of the workshop has resulted in a wide range of topics addressed over the past 9 years, from basic mechanisms in aging and HIV pathogenesis, to epidemiology of aging within large cohorts, interventions, and implementation of clinical programs. Herein, we summarize the key topics discussed at the 9th Annual International Workshop on HIV and Aging 2018, including "inflammaging," mitochondrial dysfunction, exercise interventions, HIV-associated neurocognitive impairment, metabolic dysfunction, menopause, and polypharmacy. In addition to recent developments in research and clinical care, we discuss open questions and future research directions required to better understand the interaction of HIV and aging.

18.
Front Pharmacol ; 10: 721, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333454

RESUMO

As pre-exposure prophylaxis (PrEP) effectiveness is strongly linked to adherence, we sought to determine if certain self-report measures could be used to inform objective PrEP adherence. We studied participants from the TAPIR study (a multicenter randomized study of daily text messages to support adherence to PrEP In At-Risk), a 48-week randomized controlled trial of HIV-uninfected men who have sex with men (MSM) randomized to receive text message to support adherence versus standard of care. Self-reported medication adherence was assessed using several validated measures modified for PrEP. Objective PrEP adherence was determined through dried blood spot (DBS) measurement of intracellular tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP). A summary of adherence was estimated using responses to the seven adherence items at weeks 12 and 48 using confirmatory factor analysis. Correlations between self-report questions and drug concentrations were estimated with Pearson's correlations for continuous outcomes and point-biserial correlations for dichotomous outcomes. Receiver operating characteristic (ROC) analyses were conducted to assess the performance of self-report measures in predicting protective or perfect TFV-DP concentrations. Of the 369 participants who completed week 12 or 48 visits, the mean age was 35 (standard deviation 9 years), with 79% White, 12% Black, and 29% Hispanic. Correlations between self-report measures of adherence (both individual items and the adherence factor) and quantifiable FTC-TP and continuous TFV-DP concentrations showed that all self-report measures were significantly associated with these objective measures. Compared to a summary measure of self-reported adherence, the 4-week percent taken question medication recall was the only self-report item similarly or more strongly associated with recent adherence and long-term protective and perfect adherence at weeks 12 and 48. ROC analysis also showed that 4-week percent taken question had a reasonable AUC (0.798 at week 12 and 0.758 at week 48) in predicting protective TFV-DP concentrations. All single-item self-report questions assessing PrEP adherence were significantly associated with biomarker quantification, with the 4-week percent taken question performing best. Therefore, in the absence of drug concentration measurements, a 4-week self-report percent taken question may be a good single-item measure of PrEP adherence.

19.
AIDS Res Hum Retroviruses ; 35(11-12): 1044-1053, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303012

RESUMO

HIV and methamphetamine (MA) use disorder are commonly comorbid and individually associated with adverse health consequences, including frailty; however, less is known about the combined effects of both conditions. The current cross-sectional study examined how HIV and lifetime MA use disorder relate to frailty and explored associations between frailty and relevant clinical outcomes (i.e., neurocognitive and everyday functioning). Participants were categorized into three groups based on HIV status and lifetime MA diagnosis: HIV+/MA+ (n = 43), HIV+/MA- (n = 75), and HIV-/MA- (n = 92). A frailty index score (representing proportion of accumulated multisystem deficits) was calculated from 27 medical and psychiatric deficits. Multiple regression was used to examine frailty index score by HIV/MA group. Additional multiple regression models examined the interaction between frailty and HIV/MA group on cognitive and everyday functioning. Comorbid HIV+/MA+ participants had higher frailty index scores than both HIV-/MA- (b = -0.13, p < .001) and HIV+/MA- participants (b = -0.06, p = .007). Additional models linked higher frailty index score to worse global neurocognition (b = -17.6, p = .018) and greater likelihood of everyday functioning dependence (odds ratio = 1.56, p = .021). Although these relationships did not significantly differ by HIV/MA status, group-stratified analyses showed that associations of frailty with neurocognitive and everyday functioning were strongest among the HIV+/MA+ group. Multimodal public health interventions aimed at reducing frailty may help to decrease the likelihood of neurocognitive and everyday functioning problems. Current findings additionally lay groundwork for future longitudinal research examining whether frailty predicts onset of neurocognitive and functional decline in individuals with comorbid HIV and MA use disorder.

20.
J Neurovirol ; 25(6): 853-865, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31286441

RESUMO

Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.

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