Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function.

Although Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Furthermore, the overexpression of MORC2 resulted in decreased expression levels of E-cadherin. In addition, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that MORC2 interacts with HDAC1 and gets recruited onto the E-cadherin promoter to inhibit its transcription, thereby suppress its expression. Consequently, knockdown of HDAC1 in MORC2-overexpressing cells led to reduced cancer cell migration and invasion. Interestingly, we noticed that MORC2-regulated glucose metabolism via c-Myc, and LDHA, also modulates the expression of E-cadherin. Collectively, these results demonstrate for the first time a mechanistic role for MORC2 as an upstream regulator of E-cadherin expression and its associated functions in breast cancer.

The use of video job-aids to improve the quality of seasonal malaria chemoprevention delivery.

Mobile phones are increasingly used in community health programmes, but the use of video job-aids that can be displayed on smart phones has not been widely exploited. We investigated the use of video job-aids to support the delivery of seasonal malaria chemoprevention (SMC) in countries in West and Central Africa. The study was prompted by the need for training tools that could be used in a socially distanced manner during the COVID-19 pandemic. Animated videos were developed in English, French, Portuguese, Fula and Hausa, illustrating key steps for administering SMC safely, including wearing masks, washing hands, and social distancing. Through a consultative process with the national malaria programmes of countries using SMC, successive versions of the script and videos were reviewed to ensure accurate and relevant content. Online workshops were held with programme managers to plan how to use the videos in SMC staff training and supervision, and the use of the videos was evaluated in Guinea through focus groups and in-depth interviews with drug distributors and other staff involved in SMC delivery and through direct observations of SMC administration. Programme managers found the videos useful as they reinforce messages, can be viewed at any time and repeatedly, and when used during training sessions, provide a focus of discussion and support for trainers and help retain messages. Managers requested that local specificities of SMC delivery in their setting be included in tailored versions of the video for their country, and videos were required to be narrated in a variety of local languages. In Guinea, SMC drug distributors found the video covered the all the essential steps and found the video easy to understand. However, not all key messages were followed as some of the safety measures, social distancing and wearing masks, were perceived by some as creating mistrust amongst communities. Video job-aids can potentially provide an efficient means of reaching large numbers of drug distributors with guidance for safe and effective distribution of SMC. Not all distributors use android phones, but SMC programmes are increasingly providing drug distributors with android devices to track delivery, and personal ownership of smartphones in sub-Saharan Africa is growing. The use of video job-aids for community health workers to improve the quality delivery of SMC, or of other primary health care interventions, should be more widely evaluated.

The chromatin modifier MORC2 affects glucose metabolism by regulating the expression of lactate dehydrogenase A through a feed forward loop with c-Myc.

Microrchidia family CW-type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose-inducible gene and a target of c-Myc. Our meta-analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF-7 and BT-549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose-inducible gene, modulates the migration of breast cancer cells through the MORC2-c-Myc-LDHA axis.

Implementing a multi-sectoral response to HIV: a case study of AIDS councils in the Mpumalanga Province, South Africa.

BACKGROUND: A multi-sectoral response is advocated by international organisations as a good strategy to address the multiple drivers and impact of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and was historically mandated as a condition of funding. In March 2017, the South African National AIDS Council (SANAC) launched the latest 5 year National Strategic Plan (NSP) to address HIV, sexually transmitted infections and tuberculosis. As with previous iterations, the NSP calls for multi-sectoral action (MSA) and mandates AIDS councils (ACs) at different levels to coordinate its implementation. Efforts have been made to advocate for the adoption of MSA in South Africa, yet evaluation of these efforts is currently limited. OBJECTIVE: This paper assesses the implementation of a multi-sectoral response to HIV in South Africa, through a case study of the Mpumalanga Province. METHODS: We identified and reviewed key policy documents, conducted 12 interviews and held six focus group discussions. We also drew on our involvement, through participant observation, in the development of NSPs and in AC meetings. RESULTS: SANAC is struggling to provide much-needed support to provincial, district and local ACs. Therefore, most ACs are generally weak and failing to implement MSA. Membership is voluntary, there is a lack of sustained commitment and they do not include representatives from all sectors. There is little capacity to undertake the activities necessary for coordinating the implementation of MSA, and unclear roles and responsibilities within ACs result in divisions and tension between sectors. There is inadequate senior political leadership and funding to facilitate effective implementation of MSA. CONCLUSION: We identified three interventions that we argue are required to support the effective implementation of MSA: strengthening and stabilising the SANAC structure; building capacity of ACs; and creating an enabling environment for effective implementation of MSA through political leadership, support and resourcing of the HIV response.

Widening participation in nurse education: An integrative literature review.

BACKGROUND: Widening participation into higher education is espoused within educational policy in the UK, and internationally, as a mechanism to promote equality and social mobility. As nurse education is located within higher education it has a responsibility to promote widening participation within pre-registration educational programmes. It could also be argued that the profession has a responsibility to promote equality to ensure its' workforce is as diverse as possible in order to best address the health needs of diverse populations. OBJECTIVES: To undertake an integrative review on published papers exploring Widening Participation in undergraduate, pre-registration nurse education in the UK. DESIGN: A six step integrative review methodology was utilised, reviewing papers published in English from 2013-2016. DATA SOURCES: Search of CINAHL, Education Source, MEDLINE, PsychINFO, SocINDEX, Science Direct, Business Source Complete, ERIC, British Library ETOS, Teacher Reference Centre, Informit Health Collection and Informit Humanities and Social Science Collection which highlighted 449 citations; from these 14 papers met the review inclusion criteria. REVIEW METHODS: Both empirical studies and editorials focusing upon widening participation in pre-registration nurse education in the UK (2013-2016) were included. Papers excluded were non UK papers or papers not focussed upon widening participation in pre-registration nursing education. Research papers included in the review were assessed for quality using appropriate critical appraisal tools. RESULTS: 14 papers were included in the review; these were analysed thematically identifying four themes; knowledge and identification of WP, pedagogy and WP, attrition and retention and career prospects. CONCLUSIONS: Whilst widening participation is a key issue for both nurse education and the wider profession there is a lack of conceptualisation and focus regarding mechanisms to both encourage and support a wider diversity of entrant. Whilst there are some studies, these focus on particular individual widening participation groups rather than a wider strategic focus across the student lifecycle.

The role of material deprivation and consumerism in the decisions to engage in transactional sex among young people in the urban slums of Blantyre, Malawi.

Transactional sex has been associated with a high risk of HIV acquisition and unintended pregnancy among young women in urban slums in sub-Saharan Africa. However, few studies have explored the structural drivers of transactional sex from the perspective of both genders in these settings. This paper explores how young men and women understand the factors that lead to transactional sex among their peers, and how deprivation of material resources (housing, food and health care access) and consumerism (a desire for fashionable goods) may instigate transactional sex in the urban slums of Blantyre, Malawi. Data from 5 focus group discussions and 12 in-depth interviews undertaken with a total of 60 young men and women aged 18-23 years old, conducted between December 2012 and May 2013, were analysed using anticipated and grounded codes. Housing and food deprivation influenced decisions to engage in transactional sex for both young men and women. Poor health care access and a desire for fashionable goods (such as the latest hair or clothing styles and cellular phones) influenced the decisions of young women that led to transactional sex. Interventions that engage with deprivations and consumerism are essential to reducing sexual and reproductive health risks in urban slums.

Material deprivation and unemployment affect coercive sex among young people in the urban slums of Blantyre, Malawi: A multi-level approach.

We explore relations among material deprivation (measured by insufficient housing, food insecurity and poor healthcare access), socio-economic status (employment, income and education) and coercive sex. A binary logistic multi-level model is used in the estimation of data from a survey of 1071 young people aged 18-23 years, undertaken between June and July 2013, in the urban slums of Blantyre, Malawi. For young men, unemployment was associated with coercive sex (odds ratio [OR]=1.77, 95% confidence interval [CI]: 1.09-3.21) while material deprivation (OR=1.34, 95% CI: 0.75-2.39) was not. Young women in materially deprived households were more likely to report coercive sex (OR=1.37, 95% CI: 1.07-2.22) than in non-materially deprived households. Analysis of local indicators of deprivation is critical to inform the development of effective strategies to reduce coercive sex in urban slums in Malawi.

Adverse or acceptable: negotiating access to a post-apartheid health care contract.

BACKGROUND: As in many fragile and post-conflict countries, South Africa's social contract has formally changed from authoritarianism to democracy, yet access to services, including health care, remains inequitable and contested. We examine access barriers to quality health services and draw on social contract theory to explore ways in which a post-apartheid health care contract is narrated, practiced and negotiated by patients and providers. We consider implications for conceptualizing and promoting more inclusive, equitable health services in a post-conflict setting. METHODS: Using in-depth interviews with 45 patients and 67 providers, and field observations from twelve health facilities in one rural and two urban sub-districts, we explore access narratives of those seeking and delivering - negotiating - maternal health, tuberculosis and antiretroviral services in South Africa. RESULTS: Although South Africa's right to access to health care is constitutionally guaranteed, in practice, a post-apartheid health care contract is not automatically or unconditionally inclusive. Access barriers, including poverty, an under-resourced, hierarchical health system, the nature of illness and treatment, and negative attitudes and actions, create conditions for insecure or adverse incorporation into this contract, or even exclusion (sometimes temporary) from health care services. Such barriers are exacerbated by differences in the expectations that patients and providers have of each other and the contract, leading to differing, potentially conflicting, identities of inclusion and exclusion: defaulting versus suffering patients, uncaring versus overstretched providers. Conversely, caring, respectful communication, individual acts of kindness, and institutional flexibility and leadership may mitigate key access barriers and limit threats to the contract, fostering more positive forms of inclusion and facilitating easier access to health care. CONCLUSIONS: Building health in fragile and post-conflict societies requires the negotiation of a new social contract. Surfacing and engaging with differences in patient and provider expectations of this contract may contribute to more acceptable, accessible health care services. Additionally, the health system is well positioned to highlight and connect the political economy, institutions and social relationships that create and sustain identities of exclusion and inclusion - (re)politicise suffering - and co-ordinate and lead intersectoral action for overcoming affordability and availability barriers to inclusive and equitable health care services.

Material deprivation affects high sexual risk behavior among young people in urban slums, South Africa.

Young people in urban slums adopt HIV risk behaviors influenced by their neighborhood factors. Three critical factors in urban slums of Southern and Eastern Africa--the region most affected by the HIV epidemic in the world--are unmet needs of housing, food, and health care, which are associated with HIV sexual risks. Yet, there has been limited attention on how the combination of unmet needs of housing, food, and health care--i.e., material deprivation-relates to sexual risk behavior among young people in urban slums. Cross-sectional data were extracted from the LoveLife survey in South African four provinces--KwaZulu Natal, Mpumalanga, Eastern Cape, and Gauteng, to examine the association between material deprivation and sexual risk behavior among young people aged 18-23 years (263 males, 267 females) in urban slums. Adjusted logistic regression models showed that material deprivation was significantly associated with increased odds of high sexual risk taking for young men (adjusted OR = 1.20; 95 % CI = 1.10, 5.58) and young women (adjusted OR = 1.43; 95 % CI = 1.35, 3.28). Financial difficulty--a proxy for other deprivations--was the most salient influence on young women's high sexual risk taking (adjusted OR = 2.11; 95 % CI = 1.66, 2.70). Localized behavioral HIV prevention interventions should target young people in deprived households.

Outreach services to improve access to health care in South Africa: lessons from three community health worker programmes.

INTRODUCTION: In South Africa, there are renewed efforts to strengthen primary health care and community health worker (CHW) programmes. This article examines three South African CHW programmes, a small local non-governmental organisation (NGO), a local satellite of a national NGO, and a government-initiated service, that provide a range of services from home-based care, childcare, and health promotion to assist clients in overcoming poverty-related barriers to health care. METHODS: The comparative case studies, located in Eastern Cape and Gauteng, were investigated using qualitative methods. Thematic analysis was used to identify factors that constrain and enable outreach services to improve access to care. RESULTS: The local satellite (of a national NGO), successful in addressing multi-dimensional barriers to care, provided CHWs with continuous training focused on the social determinants of ill-health, regular context-related supervision, and resources such as travel and cell-phone allowances. These workers engaged with, and linked their clients to, agencies in a wide range of sectors. Relationships with participatory structures at community level stimulated coordinated responses from service providers. In contrast, an absence of these elements curtailed the ability of CHWs in the small NGO and government-initiated service to provide effective outreach services or to improve access to care. CONCLUSION: Significant investment in resources, training, and support can enable CHWs to address barriers to care by negotiating with poorly functioning government services and community participation structures.

Evaluation of an intervention to increase human immunodeficiency virus testing among youth in Manzini, Swaziland: a randomized control trial.

There is an urgent need for effective HIV prevention programs for adolescents in Swaziland, given the high prevalence of HIV and lack of HIV-related knowledge and skills among Swazi youth. This study set out to determine whether an HIV education intervention designed in the United States, and adapted for Swaziland, would be effective in changing participants' HIV-related knowledge, attitudes, and protective behaviors including HIV testing. We also explored whether the components of Self-Efficacy Theory are associated with these behaviors. Data were obtained from 135 students who participated in a school-based program. The study found significant differences between the intervention and control groups regarding HIV knowledge, self-efficacy for abstinence, condom use, and getting HIV test results, outcome expectations for knowing one's own HIV status, and the protective behavior of getting an HIV test. This is evidence that school-based HIV education programs can successfully increase HIV testing among in-school youth in Swaziland.

Urban health in Johannesburg: the importance of place in understanding intra-urban inequalities in a context of migration and HIV.

Developing country urban contexts present multiple challenges to those responsible for ensuring the good health of urban populations. These include urban growth, migration, informal settlements, intra-urban inequalities and - in some cases - high HIV prevalence. Using Johannesburg as a case study, this paper explores the complexities of the urban context by comparing the social determinants of urban health between migrant groups residing in the inner-city and a peripheral urban informal settlement. It is argued that any attempt to improve the health of urban populations in the context of migration and HIV requires understanding that 'place matters'.

Social capital and healthy urbanization in a globalized world.

This paper critically reviews the extent in which social capital can be a resource to promote health equity in urban contexts. It analyzes the concept of social capital and reviews evidence to link social capital to health outcomes and health equity, drawing on evidence from epidemiological studies and descriptive case studies from both developed and developing countries. The findings show that in certain environments social capital can be a key factor influencing health outcomes of technical interventions. Social capital can generate both the conditions necessary for mutual support and care and the mechanisms required for communities and groups to exert effective pressure to influence policy. The link between social capital and health is shown to operate through different pathways at different societal levels, but initiatives to strengthen social capital for health need to be part of a broader, holistic, social development process that also addresses upstream structural determinants of health. A clearer understanding is also needed of the complexity and dynamics of the social processes involved and their contribution to health equity and better health. The paper concludes with recommendations for policy and programming and identifies ten key elements needed to build social capital.