Effect of a 12-Week Mixed Training on Body Quality in People Living with HIV: Does Age and HIV Duration Matter?

BACKGROUND: The impact of HIV duration on exercise adaptations has not yet been studied. Moreover, the age at which subjects living with HIV are the most responsive to exercise is not clear. AIMS: Investigate the effect of a mixed exercise training program on physical performance changes in individuals living with HIV and explore if age or HIV duration influence these adaptations in men. METHODS: In this feasibility study, participants followed a 12-week mixed exercise training program, three times/week, 45 min/session. Physical performance including functional capacities (normal 4-m walking test, 6min walking test), grip strength (hand dynamometer), muscle power, body composition (android and gynoid fat masses, appendicular lean mass) were evaluated pre- and post-intervention. Subgroup analysis according to the median age of the participants (age<50yrs vs. age≥50yrs) and median HIV duration (HIV<20yrs vs. HIV≥20yrs) were performed in men. RESULTS: A total of 27 participants (age: 54.5±6.8yrs, men: 85%; HIV duration: 19.3±7.6yrs) were included. At the end of the intervention, significant increases compared to baseline were seen in grip strength (p=0.017), leg power (p<0.001), normal walking speed (p<0.001) and 6-min walking distance (p=0.003). Following the intervention, parameters improved similarly in both age groups. However improvement was greater in those with HIV>20yrs than those with a shorter infection duration, with change (%) on total (p<0.001), android (p=0.02), and gynoid (p=0.05) fat masses as well as appendicular lean mass index (p=0.03). CONCLUSION: Mixed exercise training seems to be an effective intervention to improve physical performance in individuals living with HIV. In addition, this study suggests that neither age nor HIV duration has influence on the effect of mixed training in this population.

Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis.

Joint immobility is a debilitating complication of articular trauma that is characterized by thickening and stiffening of the joint capsule and the formation of fibrotic lesions inside joints. Capsule release surgery can temporarily restore mobility, but contraction often recurs due to the contractile activities of fibroblasts, which exert tension on the capsule ECM via nonmuscle myosin II. Based on these findings we hypothesized that blebbistatin, a drug that reversibly inhibits the activity of this protein, would relax ECM tension imposed by fibroblasts and reduce fibrosis. In this study, we characterized the effectiveness of blebbistatin as an anticontractile treatment. Given that sustained suppression of contractile activity may be required to achieve capsule release and reduce fibrosis, we compared the effects on fibroblast-mediated collagen ECM displacement of blebbistatin-loaded poly(lactide-co-gylcolide) (PLGA) particles versus bolus blebbistatin dosing. Time-lapse imaging of fluorescent microspheres embedded in collagen gels confirmed that PLGA/blebbistatin inhibited force generation and reduced both gel displacement and rate of displacement. In addition, collagen production at 10 days was significantly reduced. Taken together, these data indicate that blebbistatin-loaded PLGA particles can be used to inhibit fibroblast force-generation and reduce collagen production and lay the foundation for optimization of drug delivery technology for treating arthrofibrosis.

Strain-dependent oxidant release in articular cartilage originates from mitochondria.

Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously, we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium, an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r(2) = 0.87, p < 0.05), and significant cell death was observed at strains >40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell-permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology.

Computerized testing augments pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment(*).

BACKGROUND: Existing tools for rapid cognitive assessment in HIV-positive individuals with mild cognitive deficits lack sensitivity or do not meet psychometric requirements for tracking changes in cognitive ability over time. METHODS: Seventy-five nondemented HIV-positive patients were evaluated with the Montreal Cognitive Assessment (MoCA), a brief battery of standardized neuropsychological tests, and computerized tasks evaluating frontal-executive function and processing speed. Rasch analyses were applied to the MoCA data set and subsequently to the full set of data from all tests. RESULTS: The MoCA was found to adequately measure cognitive ability as a single, global construct in this HIV-positive cohort, although it showed poorer precision for measuring patients of higher ability. Combining the additional tests with the MoCA resulted in a battery with better psychometric properties that also better targeted the range of abilities in this cohort. CONCLUSION: This application of modern test development techniques shows a path towards a quick, quantitative, global approach to cognitive assessment with promise both for initial detection and for longitudinal follow-up of cognitive impairment in patients with HIV infection.

[Psychoimmunology and AIDS: a review of the literature]. / Psychoimmunologie et SIDA: une revue de la littérature.

In recent years, several studies have been carried out concerning the effect of psychosocial factors on the course of infection due to the human immunodeficiency virus (HIV). After summarizing the current status of general knowledge in the field of psychoimmunology, this article reviews the results of studies conducted in regard to HIV. Two conclusions are reached. The first is that current research has not shown psychosocial factors to have any impact on either the immunity status of seropositive patients or the medical complications inherent to AIDS. The second conclusion is that several types of intervention, in particular psychoeducational approaches, stress management programs, and the strengthening of social and family support, give good results where the psychosocial well-being of patients is concerned and should motivate various health professionals to improve the focus of their interventions. Furthermore, significant methodological weaknesses in several indexed studies are noted, and these should be rectified to enable future studies to confirm or correct the present observations.

The dangerousness criterion for civil commitment: the problem and a possible solution.

The dangerousness criterion for civil commitment fails to specify which mental disorders justify commitment. This ambiguity is highlighted by the fact that there are patients with personality disorders or substance abuse who may be dangerous but for whom we have few effective treatments. A possible solution might be provided by adopting the American Psychiatric Association guidelines which consider severity of mental disorder and treatability in its criteria.