HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % of HIV(+) patients despite the success of combination antiretroviral drug therapy (cART) in the periphery. Of note, potential toxicity of antiretroviral drugs in the central nervous system (CNS) remains remarkably underexplored and may contribute to the persistence of HAND in the cART era. Previous studies have shown antiretrovirals (ARVs) to be neurotoxic in the peripheral nervous system in vivo and in peripheral neurons in vitro. Alterations in lipid and protein metabolism, mitochondrial damage, and oxidative stress all play a role in peripheral ARV neurotoxicity. We hypothesized that ARVs also induce cellular stresses in the CNS, ultimately leading to neuronal damage and contributing to the changing clinical and pathological picture seen in HIV-positive patients in the cART era. In this report, we show that ARVs are neurotoxic in the CNS in both pigtail macaques and rats in vivo. Furthermore, in vitro, ARVs lead to accumulation of reactive oxygen species (ROS), and ultimately induction of neuronal damage and death. Whereas ARVs alone caused some activation of the endogenous antioxidant response in vitro, augmentation of this response by a fumaric acid ester, monomethyl fumarate (MMF), blocked ARV-induced ROS generation, and neuronal damage/death. These findings implicate oxidative stress as a contributor to the underlying mechanisms of ARV-induced neurotoxicity and will provide an access point for adjunctive therapies to complement ARV therapy and reduce neurotoxicity in this patient population.

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Despite substantial reductions in recent years in Nepal, stunting prevalence in children younger than 5 years remains high and represents a leading public health concern. To identify factors contributing to the stunting burden, we report multilevel risk factors associated with stunting in 4,853 children aged 6-59 months in a nationally and agroecologically representative random sample from the first year of the Policy and Science for Health, Agriculture, and Nutrition Community Studies, a community-based observational, mixed-panel study. Mixed effects logistic regressions controlling for multilevel clustering in the study design were used to examine the association of individual-, household-, and community-level factors associated with stunting.Stunting prevalence was 38% in our sample. After adjustment for potential confounding variables, maternal factors, including maternal height and education, were generally the strongest individ- Although most factors associated with stunting are not rapidly modifiable, areas for future research and possible interventions emerged.