Predictors of early menopause in HIV-infected women: a prospective cohort study.

OBJECTIVE: This study sought to investigate the age at natural menopause and its predictors in a cohort of human immunodeficiency virus (HIV)-infected women in Rio de Janeiro, Brazil. STUDY DESIGN: HIV-infected women ≥30 years of age were included. Menopause was defined as having ≥1 year since the last menstrual period. Early age at natural menopause was defined as the onset of menopause at ≤45 years of age. Multivariate Cox proportional hazards analysis was applied. RESULTS: A total of 667 women were included, and the median age at baseline was 34.9 years (interquartile range, 30.9-40.5 years). In all, 507 (76%) women were premenopausal, and 160 (24%) reached menopause during the observational period; of these, 36 of 160 (27%) had early menopause. The median age at natural menopause was 48 years (interquartile range, 45-50 years). Menarche at <11 years of age (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.23-3.37), cigarette smoking during the observational period (HR, 1.59; 95% CI, 1.08-2.33), chronic hepatitis C virus (HCV) infection (HR, 2.53; 95% CI, 1.27-5.07), and CD4 count <50 cells/mm(3) (HR, 3.07; 95% CI, 1.07-8.80) were significantly associated with an earlier age at natural menopause. The magnitudes of the effects of menarche at <11 years of age (HR, 2.7; 95% CI, 1.23-5.94), cigarette smoking during the observational period (HR, 3.00; 95% CI, 1.39-6.45), chronic HCV infection (HR, 6.26; 95% CI, 2.12-18.52), and CD4 count <50 cells/mm(3) (HR, 6.64; 95% CI, 1.91-23.20) were much higher and significantly associated with early natural menopause. CONCLUSION: Early natural menopause was frequent among the HIV-infected women. In addition to menarche and cigarette smoking, which are menopausal factors among women in general, HIV-related immunodeficiency and chronic HCV were additional predictors for an earlier age at natural menopause. Adequate management of HIV in women is critical, as early onset of menopause has been associated with increased morbidity and mortality.

Invasive Pneumococcal Disease in People Living with HIV: A Retrospective Case-Control Study in Brazil.

HIV-infected patients are at particular risk for invasive pneumococcal disease (IPD). We describe cases of IPD in people living with HIV/AIDS (PLWHA) and find associated risk factors for infection and death. METHODS: A retrospective case-control study, nested in a cohort, including PLWHA with and without IPD, conducted in Brazil, 2005-2020. Controls were of the same gender/age and seen at the same time/place as cases. RESULTS: We identified 55 episodes of IPD (cases) in 45 patients and 108 controls. The incidence of IPD was 964/100,000 person-years. A total of 42 of 55 (76.4%) IPD episodes presented with pneumonia and 11 (20%) with bacteremia without a focus and 38/45 (84.4%) were hospitalized. Blood cultures were positive in 54/55 (98.2%). Liver cirrhosis and COPD were the only factors associated with IPD in PLWHA in univariate analysis, although no associated factors were found in multivariate analysis. Penicillin resistance was found in 4/45 (8.9%). Regarding antiretroviral therapy (ART), 40/45 (88.9%) cases vs. 80/102 controls (74.1%) were in use (p = 0.07). Patients with HIV and IPD had a higher CD4 count of 267 cells/mm3 compared with the control group, in which it was 140 cells/mm3 (p = 0.027). Pneumococcal vaccination was documented in 19%. Alcoholism (p = 0.018), hepatic cirrhosis (p = 0.003), and lower nadir CD4 count (p = 0.033) were associated with the risk of death in patients with IPD. In-hospital mortality among PLWHA and IPD was 21.1%, and it was associated with thrombocytopenia and hypoalbuminemia, elevated band forms, creatinine, and aspartate aminotransferase (AST). CONCLUSIONS: The incidence of IPD in PLWHA remained high despite ART. The vaccination rate was low. Liver cirrhosis was associated with IPD and death.

Hypocaloric diet with lower meal frequency did not affect weight loss, body composition and insulin responsiveness, but improved lipid profile: a randomized clinical trial.

Dietary approaches are essential to control obesity, but the effectiveness of changes in meal frequency (MF) as a strategy for body weight loss or maintenance remain unclear. This study aimed to evaluate the influence of MF of a hypocaloric diet on weight loss, body composition, active ghrelin levels and metabolic indicators of obese women. This is a randomized, parallel clinical trial, including 40 women divided into two groups that received a hypocaloric diet with different MFs: MF6: six meals per day, and MF3: three meals per day. Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of the intervention. Dietary consumption did not differ between groups, before or after intervention. The two groups reduced their energy intake after intervention, but there were no differences between the groups. Waist circumference (WC) was reduced and resting metabolic rate had increased in the MF3 group at the end compared to baseline. Moreover, there was a significant difference in the triglyceride levels between groups after intervention, with an important reduction in the MF3 group, although changes in body composition, blood glucose, plasma ghrelin levels and EE variables did not differ between the groups at the end. It is concluded that, the hypocaloric diet with different MF each day did not change weight loss, body composition or insulin responsiveness, but there was an improvement of triglyceridemia in the MF3 group. The present study suggests that eating snacks between meals is not an important factor for weight loss and improvement of metabolic health in women with obesity.

miRNA expression in control and FSHD fetal human muscle biopsies.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. METHODS: Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. RESULTS: During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. CONCLUSIONS: This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.

HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System

Abstract Background: The mechanisms through which HTLV-1 leads to and maintains damage in the central nervous system of patients undergoing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are still poorly understood. In recent years, increasing evidence indicates that, not only lymphocytes but also glial cells, in particular astrocytes, play a role in the pathophysiology of HAM/TSP. In this study we used a model of co-culture between human HTLV-1-infected (CIB and C91PL) and non-infected (CEM) T lymphocyte cell lines and astrocyte (U251 and U87) cell lines to mimic the in vivo T cell-astrocyte interactions. Results: We first observed that CIB and C91PL adhere strongly to cultured astrocytes cell lines, and that co-cultures of HTLV-1 infected and astrocyte cell lines cells resulted in rapid syncytium formation, accompanied by severe morphological alterations and increased apoptotic cell death of astrocyte cells. Additionally, cultures of astrocyte cell lines in presence of supernatants harvested from HTLV-1-infected T cell cultures resulted in significant increase in the mRNA of CCL2, CXCL1, CXCL2, CXCL3, CXCL10, IL-13, IL-8, NFKB1, TLR4, TNF, MMP8 and VCAM1, as compared with the values obtained when we applied supernatants of non-infected T- cell lines. Lastly, soluble factors secreted by cultured astrocytic cell lines primed through 1-h interaction with infected T cell lines, further enhanced migratory responses, as compared to the effect seen when supernatants from astrocytic cell lines were primed with non-infected T cell lines. Conclusion: Collectively, our results show that HTLV-1 infected T lymphocyte cell lines interact strongly with astrocyte cell lines, leading to astrocyte damage and increased secretion of attracting cytokines, which in turn may participate in the further attraction of HTLV-1-infected T cells into central nervous system (CNS), thus amplifying and prolonging the immune damage of CNS.