Immune Dysregulation Is Associated with Neurodevelopment and Neurocognitive Performance in HIV Pediatric Populations—A Scoping Review

HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric populations are not well understood, we conducted a scoping review on this topic. The study aimed to systematically review the association of blood and cerebrospinal fluid (CSF) immune markers with neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Studies were selected based on a set eligibility criterion. Titles, abstracts, and full texts were assessed by two independent reviewers. Data from the selected studies were extracted and analyzed by two independent reviewers. Seven studies were considered eligible for use in this context, which included four cross-sectional and three longitudinal studies. An average of 130 (±70.61) children living with HIV, 138 (±65.37) children exposed to HIV but uninfected and 90 (±86.66) HIV-negative participants were included across the seven studies. Results indicate that blood and CSF immune markers are associated with neurocognitive development/performance in pediatric HIV populations. Only seven studies met the inclusion criteria, therefore, these limited the number of significant conclusions which could have been made by using such an approach. All considered, the evidence suggests that immune dysregulation, as in the case of adult HIV populations, also has a significant association with neurocognitive performance in pediatric HIV populations

Co-Creative Action Research Experiments—A Careful Method for Causal Inference and Societal Impact

The rigor-versus-relevance debate in the world of academia is, by now, an old-time classic that does not seem to go away so easily. The grassroots movement Responsible Research in Business and Management, for instance, is a very active and prominent advocate of the need to change current research practices in the management domain, broadly defined. One of its main critiques is that current research practices are not apt to address day-to-day management challenges, nor do they allow such management challenges to feed into academic research. In this paper, we address this issue, and present a research design, referred to as CARE, that is aimed at building a bridge from rigor to relevance, and vice versa. In so doing, we offer a template for conducting rigorous research with immediate impact, contributing to solving issues that businesses are struggling with through a design that facilitates causal inference

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Privacy rights of human research participants in South Africa must be taken seriously

Letter by Thaldar and Townsend, following an article by the same authors (Thaldar D, Townsend B. Genomic research and privacy: A response to Staunton et al. S Afr Med J 2020;110(3):172-174. https://doi.org/10.7196/SAMJ.2020.v110i3.14431) and both commenting on an article by Staunton et al. (Staunton C, Adams R, Botes M, et al. Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013. S Afr Med J 2019;109(7):468-470. https://doi.org/10.7196/SAMJ.2019.v109i7.14148); and response to article and letter by Staunton et al

Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV:The GOLD Depression Study

People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (β = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, β = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, β = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1β, β = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression

Modification of Collagen by 3-Deoxyglucosone Alters Wound Healing through Differential Regulation of p38 MAP Kinase

Background: Wound healing is a highly dynamic process that requires signaling from the extracellular matrix to the fibroblasts for migration and proliferation, and closure of the wound. This rate of wound closure is impaired in diabetes, which may be due to the increased levels of the precursor for advanced glycation end products, 3-deoxyglucosone (3DG). Previous studies suggest a differential role for p38 mitogen-activated kinase (MAPK) during wound healing; whereby, p38 MAPK acts as a growth kinase during normal wound healing, but acts as a stress kinase during diabetic wound repair. Therefore, we investigated the signaling cross-talk by which p38 MAPK mediates wound healing in fibroblasts cultured on native collagen and 3DG-collagen. Methodology/Principal Findings: Using human dermal fibroblasts cultured on 3DG-collagen as a model of diabetic wounds, we demonstrated that p38 MAPK can promote either cell growth or cell death, and this was dependent on the activation of AKT and ERK1/2. Wound closure on native collagen was dependent on p38 MAPK phosphorylation of AKT and ERK1/2. Furthermore, proliferation and collagen production in fibroblasts cultured on native collagen was dependent on p38 MAPK regulation of AKT and ERK1/2. In contrast, 3DG-collagen decreased fibroblast migration, proliferation, and collagen expression through ERK1/2 and AKT downregulation via p38 MAPK. Conclusions/Significance: Taken together, the present study shows that p38 MAPK is a key signaling molecule that plays

Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone