Impact of Antiretroviral Therapy on Health-Related Quality of Life among South African Women in the CAPRISA 002 Acute Infection Study

Concerns are often raised regarding potentially adverse effects of antiretroviral therapy (ART) on health-related quality of life (HRQoL), but there is limited longitudinal data to prove this. Building on our prior investigation, we examined the impact of ART on HRQoL among HIV-infected South African women with extensive follow-up in the CAPRISA 002 Acute Infection Cohort Study. Overall HRQoL and five sub-domains [physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB) and cognitive functioning (CF)] were assessed using the Functional Assessment of HIV Infection (FAHI) instrument. Our analyses comparing FAHI scores between pre-ART (established infection) and ART phases using paired Wilcoxon signed-rank tests and adjusted mixed-effects regression models revealed improvements on ART in overall HRQoL, and in PWB, EWB, and SWB, but not in FGWB and CF. No long-term adverse impact of ART on HRQoL was detected, providing additional non-biomedical support to early treatment strategies.     

Disclosure of Microbicide Gel Use to Sexual Partners: Influence on Adherence in the CAPRISA 004 Trial

Young women in sub-Saharan Africa are disproportionately affected by HIV, making the development of women initiated and controlled methods of prevention, including microbicides, a priority. Adherence is pivotal to microbicide efficacy and partner related factors are known to impact adherence. An analysis of disclosure of gel use to sexual partners and adherence in CAPRISA 004 women was conducted to better understand this relationship. Partner disclosure was significantly associated with a modest 4.2 % increased adherence (71.0 vs. 66.8 %, p = 0.03). Most women rated the experience of disclosure as positive, despite 6.7 % of partners expressing a negative reaction.Participants who disclosed were more likely to reside with their regular partner (14.4 vs. 8.4 %; p = 0.01) and reported consistent condom use at baseline (32.9 vs. 20.9 %; p < 0.01). Partner disclosure needs to be better understood as a potential facilitator or barrier to microbicide adherence.     

Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice

Aim: Recent studies have demonstrated that selective sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism.Method: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE^−/−) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed.Result: Canagliflozin decreased blood glucose (P < 0.001) and total cholesterol (P < 0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P < 0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P < 0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P < 0.05, both). Methylglyoxal also decreased the phosphorylation of eNOS^Ser1177 and Akt but increased the phosphorylation of eNOS^Thr495 and p38 MAPK in HUVECs.Conclusion: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE^−/− mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.     

Adaptation of adherent-invasive E. coli to gut environment: Impact on flagellum expression and bacterial colonization ability

ABSTRACT

The pathogenesis of Crohn's disease (CD) is multifactorial and involves genetic susceptibility, environmental triggers and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are flagellated bacteria more prevalent in CD patients than in healthy subjects and promote chronic intestinal inflammation. We aim at deciphering the role of flagella and flagellin modulation by intestinal conditions. AIEC flagellum expression is required for optimal adhesion to and invasion of intestinal epithelial cells. Interestingly, differential flagellin regulation was observed between commensal E. coli (HS) and AIEC (LF82) strains: flagellum expression by AIEC bacteria, in contrast to that of commensal E. coli, is enhanced under intestinal conditions (the presence of bile acids and mucins). Flagella are involved in the ability of the AIEC LF82 strain to cross a mucus layer in vitro and in vivo, conferring a selective advantage in penetrating the mucus layer and reaching the epithelial surface. In a CEABAC10 mouse model, a non-motile mutant (LF82-ΔfliC) exhibits reduced colonization that is restored by a dextran sodium sulfate treatment that alters mucus layer integrity. Moreover, a mutant that continuously secretes flagellin (LF82-ΔflgM) triggers a stronger inflammatory response than the wild-type strain, and the mutant's ability to colonize the CEABAC10 mouse model is decreased. Overexpression of flagellin in bacteria in contact with epithelial cells can be detrimental to their virulence by inducing acute inflammation that enhances AIEC clearance. AIEC pathobionts must finely modulate flagellum expression during the infection process, taking advantage of their specific virulence gene regulation to improve their adaptability and flexibility within the gut environment.     

Congenital Hypothyroidism and the Importance of Universal Newborn Screening

Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation in children. Early diagnosis and treatment prevent the devastating outcome of mental retardation. Clinical features of CH are subtle and are not evident early in the neonatal period. Therefore, universal newborn screening (NS) is effective in detecting CH and implementing early treatment. This article reviews the current literature regarding the epidemiology, etiology, classification, clinical features, diagnosis of primary CH, and the management of abnormal newborn screen as well as treatment and prognosis of primary CH and outlines the importance of universal newborn screening in preventing mental retardation.