Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile.

BACKGROUND: The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs). METHODS: 40 PHIV participants initiated ART during infancy. 39 participant samples were available; 30 initiated ART ≤6 months (early-ART treatment); 9 initiated ART >6 months and <2 years (late-ART treatment). We compared plasma cytokine and chemokine concentrations and ADA enzymatic activities between early-ART and late-ART treatment 12.5 years later and measured correlation with clinical covariates. RESULTS: Plasma concentrations of 10 cytokines and chemokines (IFNγ, IL-12p70, IL-13, IL-17A, IL-IRA, IL-5, IL-6, and IL-9 as well as CCL7, CXCL10), ADA1, and ADA total were significantly higher in late-ART compared to early-ART treatment. Furthermore, ADA1 was significantly positively correlated with IFNγ, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFNγ, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7. CONCLUSIONS: Elevation of several pro-inflammatory plasma analytes in late-ART despite 12.5 years of virologic suppression compared to early-ART treatment suggests that early treatment dampens the long-term plasma inflammatory profile in PHIV participants. IMPACT: This study examines differences in the plasma cytokine, chemokine, and ADA profiles 12.5 years after treatment between early (≤6months) and late (>6 months and <2 years) antiretroviral therapy (ART) treatment initiation in a cohort of European and UK study participants living with PHIV. Several cytokines and chemokines (e.g., IFNγ, IL-12p70, IL-6, and CXCL10) as well as ADA-1 are elevated in late-ART treatment in comparison to early-ART treatment. Our results suggest that effective ART treatment initiated within 6 months of life in PHIV participants dampens a long-term inflammatory plasma profile as compared to late-ART treatment.

Movement Behavior and Health Outcomes among Sedentary Adults: A Cross-Sectional Study.

BACKGROUND: Sedentary behavior, which is highly prevalent among office workers, is associated with multiple health disorders, including those of the musculoskeletal and cardiometabolic systems. Although prior studies looked at postures or physical activity during work or leisure time, few analyzed both posture and movement throughout the entire day. OBJECTIVE: This cross-sectional pilot study examined the movement behavior of sedentary office workers during both work and leisure time to explore its association with musculoskeletal discomfort (MSD) and cardiometabolic health indicators. METHODS: Twenty-six participants completed a survey and wore a thigh-based inertial measuring unit (IMU) to quantify the time spent in different postures, the number of transitions between postures, and the step count during work and leisure time. A heart rate monitor and ambulatory blood pressure cuff were worn to quantify cardiometabolic measures. The associations between movement behavior, MSD, and cardiometabolic health indicators were evaluated. RESULTS: The number of transitions differed significantly between those with and without MSD. Correlations were found between MSD, time spent sitting, and posture transitions. Posture transitions had negative correlations with body mass index and heart rate. CONCLUSIONS: Although no single behavior was highly correlated with health outcomes, these correlations suggest that a combination of increasing standing time, walking time, and the number of transitions between postures during both work and leisure time was associated with positive musculoskeletal and cardiometabolic health indicators among sedentary office workers and should be considered in future research.

Postural strategies among office workers during a prolonged sitting bout.

Sedentary behavior has increased steadily over prior decades, primarily due to increased computer use at work and at home. The total sedentary time per day has been associated with increased risk of cardiometabolic diseases; increased sitting time at work has been associated with musculoskeletal discomfort particularly in the low back. Office workers spend many hours sitting, thus efforts to increase movement through changes of posture (sit to stand) or moving while sitting have been proposed as ways to mitigate the negative effects of prolonged sitting. Yet, few studies have investigated differences in the movement patterns of office workers while sitting performing their actual work. Therefore, the aim of this study was to characterize movement patterns during a prolonged sitting bout and to determine their association with musculoskeletal pain. Twenty-eight office workers participated in this field study that used a pressure sensitive mat to quantify seat pan pressure (4 regions) and trunk sway parameters over a 2-hour bout of computer work. Data were stratified by breakers who stood up at least once within the 2-hour test and prolongers who remained sitting throughout the test. Overall, there was a decreasing trend in trunk sway parameters (mean COP position, sway path, sway area, sway velocity, maximum displacement, and in-chair movements) over time (p < 0.05), with significant changes in sitting strategies. There were significant differences in trunk sway parameters and perceived musculoskeletal discomfort between breakers and prolongers with breakers having more consistent movement while sitting over the prolonged sitting bout (p < 0.05) and lower discomfort ratings. This may indicate that interrupting prolonged bouts of sitting with short periods of standing can maintain sitting movement patterns and reduce the development of musculoskeletal discomfort. Trunk sway monitoring and promoting periodic standing may be useful tools for maintaining in chair movements that may reduce or prevent the onset of musculoskeletal discomfort during prolonged sitting.

Kinetic modeling of H2O2 dynamics in the mitochondria of HeLa cells.

Hydrogen peroxide (H2O2) promotes a range of phenotypes depending on its intracellular concentration and dosing kinetics, including cell death. While this qualitative relationship has been well established, the quantitative and mechanistic aspects of H2O2 signaling are still being elucidated. Mitochondria, a putative source of intracellular H2O2, have recently been demonstrated to be particularly vulnerable to localized H2O2 perturbations, eliciting a dramatic cell death response in comparison to similar cytosolic perturbations. We sought to improve our dynamic and mechanistic understanding of the mitochondrial H2O2 reaction network in HeLa cells by creating a kinetic model of this system and using it to explore basal and perturbed conditions. The model uses the most current quantitative proteomic and kinetic data available to predict reaction rates and steady-state concentrations of H2O2 and its reaction partners within individual mitochondria. Time scales ranging from milliseconds to one hour were simulated. We predict that basal, steady-state mitochondrial H2O2 will be in the low nM range (2-4 nM) and will be inversely dependent on the total pool of peroxiredoxin-3 (Prx3). Neglecting efflux of H2O2 to the cytosol, the mitochondrial reaction network is expected to control perturbations well up to H2O2 generation rates ~50 µM/s (0.25 nmol/mg-protein/s), above which point the Prx3 system would be expected to collapse. Comparison of these results with redox Western blots of Prx3 and Prx2 oxidation states demonstrated reasonable trend agreement at short times (≤ 15 min) for a range of experimentally perturbed H2O2 generation rates. At longer times, substantial efflux of H2O2 from the mitochondria to the cytosol was evidenced by peroxiredoxin-2 (Prx2) oxidation, and Prx3 collapse was not observed. A refined model using Monte Carlo parameter sampling was used to explore rates of H2O2 efflux that could reconcile model predictions of Prx3 oxidation states with the experimental observations.

Patriarchy, power, and female masculinity.

This article examines the place of "butch" within the women's movement. The political potentials of butch in both her refusal of patriarchal constructs of femininity and her transmutation of masculinity will be explored. It will be argued that the butch lesbian threatens male power by severing the naturalized connection between masculinity and male bodies, by causing masculinity to appear "queer," and by usurping men's roles. However, for "butch" to truly have feminist potential, it also needs to be accompanied by a feminist awareness and a rejection of aspects of masculinity that are oppressive to women. Hence, "butch feminist" need not be an oxymoron, but a strategy for challenging male domination and power.