The ART Advantage: Health Care Utilization for Diabetes and Hypertension in Rural South Africa

The prevalence of diabetes and hypertension has increased in HIV-positive populations, but there is limited understanding of the role that antiretroviral therapy (ART) programs play in the delivery of services for these conditions. The aim of this study is to assess the relationship between ART use and utilization of health care services for diabetes and hypertension.Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa is a cohort of 5059 adults. The baseline study collects biomarker-based data on HIV, ART, diabetes, and hypertension and self-reported data on health care utilization. We calculated differences in care utilization for diabetes and hypertension by HIV and ART status and used multivariable logistic regressions to estimate the relationship between ART use and utilization of services for these conditions, controlling for age, sex, body mass index, education, and household wealth quintile.Mean age, body mass index, hypertension, and diabetes prevalence were lower in the HIV-positive population (all P < 0.001). Multivariable logistic regression showed that ART use was significantly associated with greater odds of blood pressure measurement [adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI): 1.04 to 1.55] and blood sugar measurement (aOR 1.26, 95% CI: 1.05 to 1.51), counseling regarding exercise (aOR 1.57, 95% CI: 1.11 to 2.22), awareness of hypertension diagnosis (aOR 1.52, 95% CI: 1.12 to 2.05), and treatment for hypertension (aOR 1.63, 95% CI: 1.21 to 2.19).HIV-positive patients who use ART are more likely to have received health care services for diabetes and hypertension. This apparent ART advantage suggests that ART programs may be a vehicle for strengthening health systems for chronic care

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis.

Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria

Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.

Essentially all biological processes depend on protein-protein interactions (PPIs). Timing of such interactions is crucial for regulatory function. Although circadian (~24-hour) clocks constitute fundamental cellular timing mechanisms regulating important physiological processes, PPI dynamics on this timescale are largely unknown. Here, we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach. Among them, the interaction of protein phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We constructed a dynamic circadian PPI network predicting the PPI timing using circadian expression data. Systematic circadian phenotyping (RNAi and overexpression) suggests a crucial role for components involved in dynamic interactions. Systems analysis of a global dynamic network in liver revealed that interacting proteins are expressed at similar times likely to restrict regulatory interactions to specific phases. Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner

Frailty and physical performance in the context of extreme poverty: a population-based study of older adults in rural Burkina Faso [version 1; peer review: 2 approved]

Background: Little is known about the prevalence of frailty and about normal values for physical performance among older individuals in low-income countries, in particular those in sub-Saharan Africa. We describe the prevalence of phenotypic frailty, and values and correlates of several physical performance measures in a cohort of middle-aged and older people living in rural Burkina Faso, one of the world’s poorest communities. Methods: We analysed data collected from participants aged over 40 in Nouna district, Burkina Faso. We measured handgrip strength, four metre walk speed, chair rise time, and derived the Fried frailty score based on grip strength, gait speed, body mass index, self-reported exhaustion, and physical activity. Frailty and physical performance indicators were then correlated with health and sociodemographic variables including comorbid disease, marital status, age, sex, wealth and activity impairment. Results: Our sample included 2973 individuals (1503 women), mean age 54 years. 1207 (43%) were categorised as non-frail, 1324 (44%) as prefrail, 212 (7%) as frail, and 167 (6%) were unable to complete all five frailty score components. Lower grip strength, longer chair stand time, lower walk speed and prevalence of frailty rose with age. Frailty was more common in women than men (8% vs 6%, p=0.01) except in those aged 80 and over. Frailty was strongly associated with impairment of activities of daily living and with lower wealth, being widowed, diabetes mellitus, hypertension, and self-reported diagnoses of tuberculosis or heart disease. With the exception of grip strength, which was higher in women than prior international normative values, women had greater deficits than men in physical performance. Conclusions: Phenotypic frailty and impaired physical performance were associated as expected with female sex, co-morbidities, increasing age and impaired activities of daily living. These results support the use of frailty measurements for classification of ageing related syndromes in this setting

HDNetDB: A Molecular Interaction Database for Network-Oriented Investigations into Huntington’s Disease

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although HD is monogenic, its molecular manifestation appears highly complex and involves multiple cellular processes. The recent application of high throughput platforms such as microarrays and mass-spectrometry has indicated multiple pathogenic routes. The massive data generated by these techniques together with the complexity of the pathogenesis, however, pose considerable challenges to researchers. Network-based methods can provide valuable tools to consolidate newly generated data with existing knowledge, and to decipher the interwoven molecular mechanisms underlying HD. To facilitate research on HD in a network-oriented manner, we have developed HDNetDB, a database that integrates molecular interactions with many HD-relevant datasets. It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). HDNetDB is publicly accessible at http://hdnetdb.sysbiolab.eu.CHDI Foundation [A-2666]; Portuguese Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/70718/2010, SFRH/BPD/96890/2013, IF/00881/2013, UID/BIM/04773/2013 - CBMR, UID/Multi/04326/2013 - CCMAR]info:eu-repo/semantics/publishedVersio

Reaching for the 'first 95': a cross-country analysis of HIV self-testing in nine countries in sub-Saharan Africa

OBJECTIVES: HIV self-testing (HIVST) offers a promising approach to increase HIV diagnosis and advance progress towards the UNAIDS 95-95-95 targets. We aimed to understand patterns of HIVST awareness and utilization in nine sub-Saharan African (SSA) countries, with the goal of identifying populations to target in disseminating this technology. DESIGN: A cross-sectional study. METHODS: We pooled individual-level population-based data from nine Demographic and Health Surveys (DHS) in SSA conducted 2015-2019 (Burundi, Cameroon, Guinea, Malawi, Senegal, Sierra Leone, South Africa, Zambia, Zimbabwe). Primary outcomes were HIVST awareness and utilization. We used logistic regression with survey fixed effects to explore the relationship between sociodemographic characteristics and these outcomes. Models were adjusted for sex, age, rural/urban residence, education, wealth, and marital status. We accounted for complex survey design. RESULTS: The study sample included 177 572 people (66.0% women, mean age 29 ± 10 years), of whom 86.6% [95% confidence interval (95% CI) 86.4-86.7] were unaware of HIVST, 11.7% (95% CI 11.6-11.9) were aware of but never used HIVST, and 1.7% (95% CI 1.6-1.8) had used HIVST. In adjusted models, women were less likely to be aware of HIVST [odds ratio (OR) 0.75, 95% CI 0.71-0.79], but more likely to have used HIVST (OR 1.17, 95% CI 1.03-1.32) compared with men. Rural residents, those who were least educated, and poorest were less likely to have heard of or used HIVST. CONCLUSION: HIVST awareness and uptake were low. Rural, less educated, and lower income populations were least likely to have heard of or used HIVST. Efforts to scale-up HIVST in these settings should aim to reach these less advantaged groups

Hypertension and diabetes control along the HIV care cascade in rural South Africa

INTRODUCTION: Participation in antiretroviral therapy (ART) programmes has been associated with greater utilization of care for hypertension and diabetes in rural South Africa. The objective of this study was to assess whether people living with HIV on ART with comorbid hypertension or diabetes also have improved chronic disease management indicators. METHODS: The Health and Aging in Africa: a longitudinal study of an INDEPTH Community in South Africa (HAALSI) is a cohort of 5059 adults >40 years old. Enrollment took place between November 2014 and November 2015. The study collected population-based data on demographics, healthcare utilization, height, weight, blood pressure (BP) and blood glucose as well as HIV infection, HIV-1 RNA viral load (VL) and ART exposure. We used regression models to determine whether HIV care cascade stage (HIV-negative, HIV+ /No ART, ART/Detected HIV VL, and ART/Undetectable VL) was associated with diagnosis or treatment of hypertension or diabetes, and systolic blood pressure and glucose among those with diagnosed hypertension or diabetes. ART use was measured from drug level testing on dried blood spots. RESULTS AND DISCUSSION: Compared to people without HIV, ART/Undetectable VL was associated with greater awareness of hypertension diagnosis (adjusted risk ratio (aRR) 1.18, 95% CI: 1.09 to 1.28) and treatment of hypertension (aRR 1.24, 95% CI: 1.10 to 1.41) among those who met hypertension diagnostic criteria. HIV care cascade stage was not significantly associated with awareness of diagnosis or treatment of diabetes. Among those with diagnosed hypertension or diabetes, ART/Undetectable VL was associated with lower mean systolic blood pressure (5.98 mm Hg, 95% CI: 9.65 to 2.32) and lower mean glucose (3.77 mmol/L, 95% CI: 6.85 to 0.69), compared to being HIV-negative. CONCLUSIONS: Participants on ART with an undetectable VL had lower systolic blood pressure and blood glucose than the HIV-negative participants. HIV treatment programmes may provide a platform for health systems strengthening for cardiometabolic disease

Evaluation of sex differences in dietary behaviours and their relationship with cardiovascular risk factors:a cross-sectional study of nationally representative surveys in seven low- and middle-income countries

Background: Cardiovascular diseases (CVD) are the leading causes of death for men and women in low-and-middle income countries (LMIC). The nutrition transition to diets high in salt, fat and sugar and low in fruit and vegetables, in parallel with increasing prevalence of diet-related CVD risk factors in LMICs, identifies the need for urgent action to reverse this trend. To aid identification of the most effective interventions it is crucial to understand whether there are sex differences in dietary behaviours related to CVD risk. Methods: From a dataset of 46 nationally representative surveys, we included data from seven countries that had recorded the same dietary behaviour measurements in adults; Bhutan, Eswatini, Georgia, Guyana, Kenya, Nepal and St Vincent and the Grenadines (2013-2017). Three dietary behaviours were investigated: positive salt use behaviour (SUB), meeting fruit and vegetable (F&V) recommendations and use of vegetable oil rather than animal fats in cooking. Generalized linear models were used to investigate the association between dietary behaviours and waist circumference (WC) and undiagnosed and diagnosed hypertension and diabetes. Interaction terms between sex and dietary behaviour were added to test for sex differences. Results: Twenty-four thousand three hundred thirty-two participants were included. More females than males reported positive SUB (31.3 vs. 27.2% p-value < 0.001), yet less met F&V recommendations (13.2 vs. 14.8%, p-value< 0.05). The prevalence of reporting all three dietary behaviours in a positive manner was 2.7%, varying by country, but not sex. Poor SUB was associated with a higher prevalence of undiagnosed hypertension for females (13.1% vs. 9.9%, p-value = 0.04), and a higher prevalence of undiagnosed diabetes for males (2.4% vs. 1.5%, p-value = 0.02). Meeting F&V recommendations was associated with a higher prevalence of high WC (24.4% vs 22.6%, p-value = 0.01), but was not associated with undiagnosed or diagnosed hypertension or diabetes. Conclusion: Interventions to increase F&V intake and positive SUBs in the included countries are urgently needed. Dietary behaviours were not notably different between sexes. However, our findings were limited by the small proportion of the population reporting positive dietary behaviours, and further research is required to understand whether associations with CVD risk factors and interactions by sex would change as the prevalence of positive behaviours increases