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Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection. [ABSTRACT FROM AUTHOR]

Pyrethroids, which are derived from natural insecticides found in chrysanthemum flowers, are widely utilized in various sectors, including agriculture, forestry, horticulture, and personal insect protection. Due to their widespread use, concerns have arisen regarding their potential estrogenic effects on female reproductive health. This review aims to address data gaps and inconsistencies in previous studies by defining molecular initiating events and key events within the adverse outcome pathway associated with pyrethroid-induced estrogenic effects. To achieve this, we propose utilizing Integrated Approaches to Testing and Assessment (IATA), which incorporate in vitro assays and in vivo assessments to comprehensively investigate the estrogenic effects of pyrethroids. An initial search was conducted in the PubMed database to identify relevant articles. Subsequently, the findings were classified according to the IATA strategy. This review provides an overview of the current understanding of pyrethroids and their estrogenic effects, identifies data gaps, and highlights the use of IATA in existing studies on the estrogenic effects of various pyrethroids. It emphasizes the urgent need for comprehensive research on the estrogenic effects of pyrethroids and highlights the importance of standardized testing methods like IATA to accurately assess their impact on human and environmental health. By promoting the use of Integrated Testing Strategies (ITSs) and addressing data gaps, researchers and regulators can enhance the accuracy of assessments, ensuring better protection of human and environmental health from the potential estrogenic effects of pyrethroid exposure. [ABSTRACT FROM AUTHOR]

The second wave of COVID-19 occurred in South America in early 2021 and was mainly driven by Gamma and Lambda variants. In this study, we aimed to describe the emergence and local genomic diversity of the SARS-CoV-2 Lambda variant in Argentina, from its initial entry into the country until its detection ceased. Molecular surveillance was conducted on 9356 samples from Argentina between October 2020 and April 2022, and sequencing, phylogenetic, and phylogeographic analyses were performed. Our findings revealed that the Lambda variant was first detected in Argentina in January 2021 and steadily increased in frequency until it peaked in April 2021, with continued detection throughout the year. Phylodynamic analyses showed that at least 18 introductions of the Lambda variant into the country occurred, with nine of them having evidence of onward local transmission. The spatial–-temporal reconstruction showed that Argentine clades were associated with Lambda sequences from Latin America and suggested an initial diversification in the Metropolitan Area of Buenos Aires before spreading to other regions in Argentina. Genetic analyses of genome sequences allowed us to describe the mutational patterns of the Argentine Lambda sequences and detect the emergence of rare mutations in an immunocompromised patient. Our study highlights the importance of genomic surveillance in identifying the introduction and geographical distribution of the SARS-CoV-2 Lambda variant, as well as in monitoring the emergence of mutations that could be involved in the evolutionary leaps that characterize variants of concern. [ABSTRACT FROM AUTHOR]

Vaccines against SARS-CoV-2 have been pivotal in overcoming the COVID-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g., people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the top cause of mortality and a main contributor to disability globally. The evidence so far is varied on whether cold or heat modifies the CVD effects of air pollution. Weather conditions and air pollution sources and levels are different in different countries. Studies in low-and middle-income countries are lacking. Mortality data were obtained from Statistics South Africa. Air pollution and meteorological data were obtained from the South African Weather Service. A time-stratified case–crossover epidemiological design was applied. The association between air pollutants (PM10, NO2 and SO2) and CVD mortality was investigated using conditional logistic regression models. Susceptibility by sex and age groups was investigated. In total, 54,356 CVD deaths were included in the 10-year study. The daily PM10, NO2 and SO2 levels exceeded the daily WHO guidelines on 463, 421 and 8 days of the 3652 days, respectively. Higher air pollution risks were observed in this study compared to those reported in meta-analyses. In general, the elderly and females seemed to be vulnerable to air pollutants, especially at high and moderate apparent temperature levels. Harvesting effects were observed at longer lags. The results can be used to develop an early warning system for the city. [ABSTRACT FROM AUTHOR]

This study investigated strategies for people with intellectual disabilities to self-advocate for inclusion of their priorities in social policy processes in South Africa. Method: Self advocacy strategies were identified through a scoping literature review, a review of self advocacy toolkits and semi structured interviews with people with intellectual disabilities and other stakeholders working at non-governmental and disabled people's organisations. These data sources were triangulated to identify strategies to upskill and support young adults with intellectual disabilities to share their opinions and perspectives to deepen the diversity of voices engaged in social policy advocacy. Results: Data triangulation identified three core strategies for self advocacy, in person, written strategies and engagement through social media. Discussion: Inclusion of people with intellectual disabilities in civic and political life is crucial, and will only be achieved if self advocates are accepted into the policy-making arena. The cycle of perpetuating exclusion needs to be disrupted, to give people with an intellectual disabilities a say in policy decisions that have an impact on their lives. Conclusion: Adopting strategies which enable the inclusion of the voices of people with intellectual disabilities in civic activities holds potential for diversifying perspectives brought to public participation in policy development and implementation, which is currently primarily the domain of non-disabled citizens. [ABSTRACT FROM AUTHOR]

The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring. [ABSTRACT FROM AUTHOR]

HIV infection requires lifelong antiretroviral therapy (ART) to control disease progression. Although ART has greatly extended the life expectancy of persons living with HIV (PWH), PWH nonetheless suffer from an increase in AIDS-related and non-AIDS related comorbidities resulting from HIV pathogenesis. Thus, an HIV cure is imperative to improve the quality of life of PWH. In this review, we discuss the origins of various SIV strains utilized in cure and comorbidity research as well as their respective animal species used. We briefly detail the life cycle of HIV and describe the pathogenesis of HIV/SIV and the integral role of chronic immune activation and inflammation on disease progression and comorbidities, with comparisons between pathogenic infections and nonpathogenic infections that occur in natural hosts of SIVs. We further discuss the various HIV cure strategies being explored with an emphasis on immunological therapies and "shock and kill". [ABSTRACT FROM AUTHOR]

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain. [ABSTRACT FROM AUTHOR]

Although West Nile virus (WNV) is endemic to South Africa (RSA), it has only become recognized as a significant cause of neurological disease in humans and horses locally in the past 2 decades, as it emerged globally. This article describes the epidemiological and clinical presentation of WNV in horses across RSA during 2016–2017. In total, 54 WNV-positive cases were identified by passive surveillance in horses with febrile and/or neurological signs at the Centre for Viral Zoonoses, University of Pretoria. They were followed up and compared to 120 randomly selected WNV-negative controls with the same case definition and during the same time period. Of the WNV-positive cases, 52% had fever, 92% displayed neurological signs, and 39% experienced mortality. Cases occurred mostly in WNV-unvaccinated horses <5 years old, during late summer and autumn after heavy rain, in the temperate to warm eastern parts of RSA. WNV-positive cases that had only neurological signs without fever were more likely to die. In the multivariable analysis, the odds of WNV infection were associated with season (late summer), higher altitude, more highly purebred animals, younger age, and failure to vaccinate against WNV. Vaccination is currently the most effective prophylactic measure to reduce WNV morbidity and mortality in horses. [ABSTRACT FROM AUTHOR]

There are no studies on the association between food insecurity and mild cognitive impairment (MCI). Thus, cross-sectional, community-based data on individuals aged ≥50 years from the World Health Organization's Study on Global AGEing and Adult Health (SAGE) conducted in South Africa (2007–2008) were analyzed to assess this association. The definition of MCI was based on the National Institute on Ageing-Alzheimer's Association criteria. Past 12-month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Multivariable logistic regression analysis was conducted. The sample consisted of 3,672 individuals aged ≥50 years [mean (SD) age 61.4 (18.3); 56% females]. The prevalence of MCI was 8.5%, while 11.0% and 20.8% experienced moderate and severe food insecurity, respectively. After adjustment for potential confounders, moderate and severe food insecurity were associated with 2.82 (95%CI = 1.65–4.84) and 2.51 (95%CI = 1.63–3.87) times higher odds for MCI compared with no food insecurity, respectively. The OR for those aged ≥65 years with severe food insecurity was particularly high (OR = 3.87; 95%CI = 2.20–6.81). In conclusion, food insecurity was strongly associated with MCI among South African older adults. Future longitudinal research is required to assess whether addressing food insecurity may reduce risk of MCI and subsequent dementia. [ABSTRACT FROM AUTHOR]

Male circumcision (MC) reduces HIV transmission risk by up to 60% in heterosexual men. However, uptake of medical male circumcision (MMC) is low in traditionally circumcising communities of South Africa. We assessed knowledge, attitudes, and practices to identify factors predicting acceptability of MMC among males in the Alfred Nzo District. A cross-sectional study was conducted among males aged 15-49 years in this district. Logistic regression was used to identify factors predicting acceptability of MMC. We interviewed 343 males who had a median age of 19 years (interquartile range (IQR): 16-25 years). Of these, 77% (95% confidence interval (CI): 72-82) were circumcised: 77% (95% CI: 71-82) were circumcised in a traditional setting and 21% (95% CI: 16-26) in a medical setting. The median score of knowledge about the benefits of MMC was 62.5% (IQR: 37.5-75.0), with 59% (95% CI: 53-64) demonstrating a positive attitude towards MMC and 68% (95% CI: 63-73) accepting involvement of health workers in MC. Excellent knowledge (adjusted odds ratio (aOR): 3.07, 95% CI: 0.99-9.58, p = 0.053), awareness (aOR: 3.26, 95% CI: 1.08-9.86, p = 0.037), and positive attitude towards MMC (aOR: 2.35, 95% CI: 1.30-4.25, p = 0.005) were associated with acceptability of MMC. Participants demonstrated good knowledge and acceptance of the MMC programme. Knowledge, attitude, and awareness were significant predictors of MMC acceptability.

The effects on respiratory health in populations living close to silica-rich gold mine dumps are unknown. This pilot study related respiratory health and exposure to mine dump dust using two measures of exposure: exposure group, based on distance lived from the mine dump-high ( n = 93) (home <500 m from a mine dump), moderate ( n = 133) (500-1.5 km), and low ( n = 84) (>15 km, control group); and cumulative exposure index (CEI) derived from exposure group and number of years of residence in each exposure group. Participants were interviewed about respiratory symptoms and had chest X-rays and spirometry. We adjusted for key respiratory confounders. No subject had radiological features of silicosis. The high relative to low exposure group had significantly elevated adjusted odds ratios (aORs) for upper respiratory symptoms (aOR: 2.76, 95% CI: 1.28-5.97), chest wheezing (aOR: 3.78; 95% CI: 1.60-8.96), and spirometry-diagnosed chronic obstructive pulmonary disease (COPD) (aOR: 8.17; 95%CI: 1.01-65.85). These findings were similar for the high relative to medium exposure group, but no significant associations were found for the medium versus low exposure group. Chronic bronchitis and tuberculosis risks did not differ significantly among groups. CEI and exposure group produced similar results. In conclusion, residents residing <500 m from mine dumps had elevated adverse respiratory health effects., Competing Interests: The authors declare no conflict of interest.