Grahamschwarz9528

Of note, microRNA (miR) profiling showed that miR-99b-3p that was predicted to target the 3'UTR of the CYLD mRNA was reduced in melanoma cell lines with high levels of CYLD compared with melanocyte lines. read more Further functional studies confirmed that the reduction in miR-99b-3p expression was responsible for the increased expression of CYLD in a highly cell line-specific manner. Taken together, these results reveal an unexpected role of CYLD in promoting survival of a subset of melanoma cells and uncover the heterogeneity of CYLD expression and its biological significance in melanoma.Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.Over the past three decades, tremendous global progress in preventing and treating paediatric HIV infection has been achieved. This paper highlights the emerging health challenges of HIV-exposed uninfected (HEU) children and the ageing population of children living with HIV (CLHIV), summarises programmatic opportunities for care, and highlights currently conducted research and remaining research priorities in high HIV-prevalence settings such as South Africa. Emerging health challenges amongst HEU children and CLHIV include preterm delivery, suboptimal growth, neurodevelopmental delay, mental health challenges, infectious disease morbidity and mortality, and acute and chronic respiratory illnesses including tuberculosis, pneumonia, bronchiectasis and lymphocytic interstitial pneumonitis. CLHIV and HEU children require three different categories of care (i) optimal routine child health services applicable to all children; (ii) routine care currently provided to all HEU children and CLHIV, such as HIV testing oerm impact of in utero ART and HIV exposure; understanding the role of preconception maternal ART on HEU child infectious morbidity and long-term growth and neurodevelopmental trajectories in HEU children and CLHIV, understanding mental health outcomes and support required in HEU children and CLHIV through childhood and adolescence; monitoring HEU child morbidity and mortality compared with HIV-unexposed children; monitoring outcomes of CLHIV who initiated ART very early in life, sometimes with suboptimal ART regimens owing to medication formulation and registration issues; and testing sustainable models of care for HEU children and CLHIV including later reproductive care and support.For several decades, researchers from the South African Medical Research Council have made invaluable contributions towards improving the health of the population through the analysis and interpretation of cause of death data. This article reflects the mortality trends in pre-and post-apartheid South Africa (SA), and describes efforts to improve vital statistics, innovations to fill data gaps, and studies to estimate the burden of disease after adjusting for data deficiencies. The profound impact of HIV/AIDS, particularly among black African children and young adults, is striking, within a protracted epidemiological transition and the current reversals of multiple epidemics. Over the next 20 years, it will be important to sustain and enhance the country's capacity to collect, analyse and utilise cause of death data. SA needs to support development in the region, harnessing new data platforms and approaches such as including verbal autopsy tools in the official system and improving data linkage.Injuries impose a fourth major disease burden on the South African population, which is driven in particular by the high incidence of interpersonal violence. There was a significant decline in mortality from interpersonal violence between 1997 and 2012, and research conducted by South African Medical Research Council (SAMRC) researchers has ascribed much of this decline to a decrease in firearm homicide. In the present brief review, we summarise South African research on fatal and non-fatal firearm injuries, with a particular focus on research conducted by SAMRC intra- and extramural units between 1969 and 2019. More recent data suggest a lapse in firearm control that has led to an increase in homicide and that the fluctuating homicide rate is being influenced by adherence to firearm control policies.A social impact bond (SIB) is an innovative financing mechanism to attract investors to social programmes traditionally funded by governments. link2 In this article, in celebration of the 50th anniversary of the South African Medical Research Council (SAMRC), the authors describe the SAMRC's first foray into this new world of financing through a SIB to improve the health and quality of life of adolescent girls and young women (AGYW). The AGYW SIB is in its preparatory phase and is scheduled for implementation in 2020. The authors describe the mechanism, including financial flows and the process of customising the SIB to meet the needs of AGYW, focusing on HIV prevention and treatment and the prevention and management of unintended pregnancies in schoolgoing AGYW. The authors outline an approach to designing the package of interventions, the metrics associated with such a programme and the business model. It is hypothesised that the proposed approach will lead to an improvement in programmatic outcomes, monitoring and evaluation tools and cost-effectiveness, and will develop key learning data for the future use of SIBs in health service delivery.A high-level review was conducted of the literature pertaining to the challenges and opportunities for eliminating malaria on the African continent. Although malaria mortality and morbidity are on the decline, the disease remains one of public health importance. Africa has invariably borne the brunt of the disease, recording the highest number of cases and deaths. However, with greater emphasis being placed on the disease by the international community, partnerships have developed to boost malaria elimination efforts on the continent. One such initiative is the Roll Back Malaria (RBM) partnership which aims to facilitate malaria elimination through increasing resources and awareness. Many cross-border initiatives have been established which treat malaria as a regional problem rather than a country-specific one. Accelerated malaria control efforts have led to a 37% decrease in cases and 60% reduction in deaths. Multi-country efforts have resulted in marked reductions of transmission in the region. Although there have been noteworthy gains in curtailing the disease, new challenges have arisen. The main among these are residual malaria and outdoor biting. One of the main drivers of residual malaria is insecticide resistance. Adding to the burden of residual transmission is the discovery of new vectors that may exist at low densities. To exacerbate these issues is the challenge of malaria imported from high- to low-transmission areas. Nevertheless, compared with the historical picture, we are winning the battle against malaria. Countries in Africa are being certified malaria-free. Partnerships have been developed to take forward the RBM Global Malaria Action Plan. Elimination agendas can only be successful if funding remains sustainable, with greater reliance on domestic funding.The South African Medical Research Council Centre for Tuberculosis Research has a rich history of high-impact research that has influenced our understating of this hyper-epidemic which is further exacerbated by the emergence and spread of drug-resistant forms of the disease. This review aims to summarise the past 30 years of research conducted in the Centre which has influenced the way that tuberculosis (TB) is diagnosed and treated. The review includes the development of new technologies for rapid screening of people with probable TB and the repurposing of human diagnostics for wildlife conservation.South Africa (SA) has one of the largest HIV/AIDS epidemics in the world and the most extensive antiretroviral therapy (ART) programme globally, which was rolled out from 2004. link3 This paper reports the trends in HIV/AIDS mortality pre and post ART rollout in SA. Methods. Vital registration cause-of-death data from Statistics South Africa were adjusted for under-reporting of deaths using demographic methods. Misattributed HIV/AIDS deaths were identified by regressing excess mortality on a lagged indicator HIV antenatal clinic prevalence for causes found to be associated with HIV/AIDS. Background trends in the source-cause mortality rates were estimated from the trend in cause-specific mortality experienced among 75 - 84-year-olds. Mortality rates were calculated using mid-year population estimates and the World Health Organization world standard age-weights. Results. We estimated over 3 189 000 HIV/AIDS deaths for 1997 - 2012. In 1997, 60 336 (14.5%) of deaths were attributed to HIV/AIDS; this number peaked in 2006 at 283 564 (41.9%) and decreased to 153 661 (29.1%) by 2012; female mortality rates peaked in 2005 and those of males in 2006. Men aged 35 years and older had higher mortality rates than did women. While the rates at ages below 65 years in 2012 were lower than those in 2006, rates of those age 65 years and older remained unchanged. Conclusion. The number of HIV/AIDS deaths has almost halved since the ART rollout. Of concern is the high mortality in men 45 years and older and the high mortality of men compared with women in the older ages by 2012; this gap has increased with age. Treatment and prevention programmes should strategise how to target men.South African (SA) researchers have made both national and global contributions to HIV prevention and treatment. Research conducted in SA has contributed markedly to improved survival in HIV-infected infants, children and adults. The translation of clinical research into practice has enabled the curtailment of paediatric HIV in SA. Along with international collaborators, SA has made pivotal contributions to biomedical prevention modalities including medical male circumcision and oral and topical microbicides, and is undertaking pivotal HIV vaccine research. Research into the structural and psychosocial drivers of HIV infection will be critical for sustaining biomedical interventions, and necessary to end AIDS.