Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement.

BACKGROUND: Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening. METHODS: We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics. RESULTS: Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress-strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression. CONCLUSION: Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.

Cardiovascular disease is the leading cause of death worldwide. Cardiovascular disease presents differently in men and women. While men develop plaque buildup in large arteries, women develop buildup in the microvessels in the heart. Arterial stiffening, which is the hardening of arteries, increases with age in both men and women. Aging, coupled with the decline in sex hormones, exacerbates cardiovascular disease in women compared to men. Men with XY sex chromosomes have higher circulating testosterone, while women with XX sex chromosomes have increased circulating estradiol. The potential benefits of sex hormone replacement therapy are shown in men and women. Indeed, testosterone replacement deficiency is associated with adverse cardiovascular outcomes in men. Whether adverse events are dependent or independent of sex hormones' interaction with sex chromosomes is unknown. This study used the four core genotype mice comprising males with either XX or XY sex chromosome complement. We show castration increases arterial stiffening and collagen deposition on the arterial wall. We also identified the escapee and smooth muscle contractile genes that may play a role in arterial stiffening. Our data suggests that testosterone deprivation mediates arterial stiffening and remodeling.

Testosterone Deficiency Promotes Arterial Stiffening Independent of Sex Chromosome Complement.

Background: Testosterone plays a vital role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening. Methods: We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated for eight weeks, followed by an assessment of blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics. Results: Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress-strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression. Conclusion: Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.

Hypertension and Associated Inflammatory Markers Among HIV-Infected Patients in Tanzania.

There remains a dearth of data regarding the association between chronic inflammation and hypertension (HTN) in sub-Saharan Africa, a region that accounts for >70% of the global burden of HIV infection. Therefore, we assessed the levels of biomarkers among HIV+ individuals and its associations with HTN in Tanzania. A cross-sectional study was conducted at one of the largest clinics in Tanzania and data from 261 HIV+ patients were analyzed. Standardized tools were used to collect data. Blood pressure was measured using Omron® M2 blood pressure monitor. Enzyme-linked immunosorbent assay was used to test for inflammatory markers [C-reactive protein (CRP), interleukin (IL)-6, IL-18, soluble tumor necrosis factor receptor type I (sTNFRI), sTNFRII]. Bivariate and multivariable analysis was conducted to examine association between the biomarkers and HTN. We further conducted age-sex-alcohol-adjusted models to control for any confounders. The prevalence of HTN was 43% with a high prevalence reported in female (70%) participants and those older than 55 years of age (77%). Being women, older than 55 years of age, married, and being overweight was associated with HTN. The highest correlations were observed between TNR2 and CRP (ɤ = 0.13, P = 0.044), and TNR2 and IL-18 (ɤ = 0.13, P = 0.034). Participants who had elevated CRP levels were 2 times more likely to experience HTN in the age-adjusted model [odds ratio (OR) = 3.5, 95% confidence interval (CI) = 1.1-11.3], age-sex-adjusted model (OR = 3.3, 95% CI = 1.0-10.9), and the full model (OR = 2.9, 95% CI = 0.8-10.0). Our study shows that high CRP levels are significantly associated with the higher prevalence of HTN notwithstanding all other markers, which showed a positive association with HTN despite not being significant. These findings point to the importance of creating awareness, education, and screening for HTN among HIV patients in high epidemic countries. More rigorous studies are needed to know the exact pathway mechanisms of inflammation in HIV patients.

Mental health symptoms and inflammatory markers among HIV infected patients in Tanzania.

BACKGROUND: HIV and mental disorders are predicted to be the leading causes of illness worldwide by the year 2030. HIV-infected patients are at increased risk of developing mental disorders which are significantly associated with negative clinical outcomes and propagation of new HIV infections. There is little evidence that links inflammation to development of mental disorders among HIV patients. Therefore, the main objective of this study was to evaluate if mental health symptoms were associated with biomarkers of inflammation in HIV infected subjects. METHODS: A cross-sectional study was conducted in Dar es Salam, Tanzania from March to May 2018. Standardized tools were used to collect data based on the World Health Organisation's (WHO) stepwise approach for non-communicable diseases (NCD) surveillance. A total of 407 HIV+ patients on antiretroviral therapy were recruited. The WHO stepwise approach for NCD surveillance was used to collect data together with anthropometric measurements. Mental health symptoms were determined based on self-reported thoughts of helplessness, suicide ideation, depression, despair, discouragement, and feelings of isolation. Enzyme-linked immunosorbent assay was used to test for inflammatory markers:- C-reactive protein (CRP), Iinterleukin-6 (IL-6), interleukin-18 (IL-18), soluble tumour necrosis factor receptor-I (sTNFR-I), and soluble tumour necrosis factor receptor-II (sTNFR-II). Bivariate and multi-variate analysis was conducted to examine the association between biomarkers and mental health symptoms. RESULTS: The prevalence of self-reported mental health symptoms was 42% (n = 169). Participants with self-reported symptoms of mental health had elevated CRP, were less likely to walk or use a bicycle for at least 10 minutes, were less likely to participate in moderate-intensity sports or fitness activities, and had poor adherence to HIV treatment (p < 0.005). CRP remained significant in the sex adjusted, age-sex adjusted, and age-sex-moderate exercise adjusted models. In the fully adjusted logistic regression model, self-reported mental health symptoms were significantly associated with a higher quartile of elevated CRP (OR 4.4; 95% CI 1.3-5.9) and sTNFR-II (OR 2.6; 95% CI 1.4-6.6) and the third quartile of IL-18 (OR 5.1;95% CI 1.5-17.5) as compared with those reporting no mental health symptoms. The significance of sTNFR-II and IL-18 in the fully adjusted model is confounded by viral load suppression rates at the sixth month. CONCLUSION: High CRP and sTNFR II were important contributors to the prevalence of mental health symptoms. This study is among the minimal studies that have examined mental health issues in HIV, and therefore, the findings may offer significant knowledge despite the potential reverse causality. Regardless of the nature of these associations, efforts should be directed toward screening, referral, and follow-up of HIV patients who are at-risk for mental health disorders.

Using Friendship Ties to Understand the Prevalence of, and Factors Associated With, Intimate Partner Violence Among Adolescents and Young Adults in Kenya: Cross-Sectional, Respondent-Driven Survey Study.

BACKGROUND: Optimization of innovative approaches is required for estimating the intimate partner violence (IPV) burden among adolescents and young adults (AYA). Further investigation is required to identify risk and protective factors associated with IPV among AYA. There remain significant gaps in understanding these factors among this vulnerable population. OBJECTIVE: The goal of our study was to determine the prevalence of IPV among an urban population of AYA and to identify factors associated with IPV among AYA. METHODS: A cross-sectional study design utilizing respondent-driven sampling was adopted. The study was conducted among 887 AYA, aged 15 to 24 years, residing in Nairobi, Kenya. Data were collected through a phone-based survey using the REACH (Reaching, Engaging Adolescents and Young Adults for Care Continuum in Health)-AYA app. Questions on behavioral and psychosocial factors were adopted from different standardized questionnaires. Descriptive, bivariate, and multivariable statistics were used to describe the characteristics of the study sample. RESULTS: Of the 887 participants, a higher proportion were male (540/887, 60.9%) compared to female (347/887, 39.1%). The prevalence of IPV was 22.3% (124/556). IPV was associated with being unsure if it was okay for a boy to hit his girlfriend, living in a home with physical violence or abuse, and being bullied (P=.005). The likelihood of experiencing IPV was higher among respondents whose friends and family members used alcohol (odds ratio [OR] 1.80, 95% CI 1.09-2.98) and among those who had repeated a class at school in the past two years (OR 1.90, 95% CI 1.11-3.23). Respondents who visited a health facility or doctor for reproductive health services were 2 times more likely to experience IPV (OR 2.23, 95% CI 1.40-3.70). Respondents who had used illicit drugs were 2 times more likely to experience IPV (OR 4.31, 95% CI 2.64-7.04). The probability of experiencing IPV decreased by 63% (OR 0.37, 95% CI 0.16-0.85) among respondents who refused to have sex with someone who was not prepared to use a condom. CONCLUSIONS: IPV remains a significant public health priority because of its impact to society. Our results are in congruence with other similar studies. Efforts toward incorporating appropriate IPV core measures into the comprehensive care package for every AYA seeking health services should be explored. Programs need to address constellations of risk and protective factors linked to IPV in an effort to prevent its occurrence.

A formative study of disposal and re-use of old mosquito nets by communities in Malindi, Kenya.

BACKGROUND: About 30 million insecticide treated mosquito nets have been distributed in Kenya since 2001 and ownership is approaching full coverage. As a consequence of this achievement, Kenya is faced with the challenge of disposing old mosquito nets that are no longer in use. The study aimed at investigating ways of disposal and re-use of old and torn nets by end users. MATERIALS AND METHODS: A formative study was conducted in the former Malindi District, which is comprised of Malindi and Magarini sub-counties of Kilifi County in Coastal Kenya. A total of 6 Focus Group Discussions, 10 Key Informant Interviews and 9 transect walks/drives were undertaken. Data from the different sources were analysed separately and triangulated for similarities and differences. RESULTS: There were variations in disposal and re-use of old nets between urban and rural or peri-urban residents. In all settings, people adopted innovative and beneficial ways of re-using old, expired nets, and those that were damaged beyond repair. Common causes of damage were fire, children, domestic animals sharing the sleeping room and friction from the bed poles while hanging or tacking it in under a sleeping mat. Re-use was most prominent in farming activities (78%) and less to for use in mosquito control, like window screening (15%). The remaining 8% was related to making ropes, swings, footballs, goal posts and fishing nets. Advantageous texture and nature of the netting material, perceived economic benefit and lack of guidelines for disposal were the main reasons cited by residents for re-using old nets. CONCLUSIONS: It is important that re-use and disposal of old mosquito nets is distinguished from misuse of newly distributed mosquito nets. Alternative uses of old nets as opposed to misuse of new nets was found to be common in our study.

Exploring communities' and health workers' perceptions of indicators and drivers of malaria decline in Malindi, Kenya.

BACKGROUND: Since 2000, a decrease in malaria burden has been observed in most endemic countries. Declining infection rates and disease burden and reduction in asymptomatic carriers are the outcome of improved quality of care and related health system factors. These include improved case management through better diagnosis, implementation of highly effective antimalarial drugs and increased use of bednets. We studied communities' and health workers' perceptions of indicators and drivers in the context of decreasing malaria transmission in Malindi, Kenya. MATERIALS AND METHODS: A variety of qualitative methods that included participatory rural appraisal (PRA) tools such as community river of life and trend lines, focus group discussions (FGDs) and key informant interviews were used. Studies took place between November 2013 and April 2014. RESULTS: Providing residents with bednets contributed to malaria reduction, and increasing community awareness on the causes and symptoms of malaria and improved malaria treatment were also perceived to contribute to the decline of malaria. The study identified three perceived drivers to the reported decline in malaria: a) community health workers' enhanced awareness creation towards household owners regarding malaria-related activities through visitations and awareness sessions, b) Women involvement in Savings Internal Lending Community was perceived to have increased their financial base, thereby improving their decision-making power towards the care of their sick child(ren), c) Non Governmental Organizations (NGOs) and partners played a promoter part in health and general economic development initiatives. CONCLUSIONS: To achieve the goal of malaria elimination, collaboration between governmental and NGOs will be crucial when improving the financial base of women and enhancing participation of community health workers.