Role of chromodomain helicase DNA-binding protein 2 in DNA damage response signaling and tumorigenesis.

The chromodomain helicase DNA-binding proteins (CHDs) are known to affect transcription through their ability to remodel chromatin and modulate histone deacetylation. In an effort to understand the functional role of the CHD2 in mammals, we have generated a Chd2 mutant mouse model. Remarkably, the Chd2 protein appears to play a critical role in the development, hematopoiesis and tumor suppression. The Chd2 heterozygous mutant mice exhibit increased extramedullary hematopoiesis and susceptibility to lymphomas. At the cellular level, Chd2 mutants are defective in hematopoietic stem cell differentiation, accumulate higher levels of the chromatin-associated DNA damage response mediator, cH2AX, and exhibit an aberrant DNA damage response after X-ray irradiation. Our data suggest a direct role for the chromatin remodeling protein in DNA damage signaling and genome stability maintenance

The roles of community health workers in management of non-communicable diseases in an urban township

BACKGROUND: Community health workers (CHWs) are increasingly being recognised as a crucial part of the health workforce in South Africa and other parts of the world. CHWs have taken on a variety of roles, including community empowerment, provision of services and linking communities with health facilities. Their roles are better understood in the areas of maternal and child health and infectious diseases (HIV infection, malaria and tuberculosis). AIM: This study seeks to explore the current roles of CHWs working with non-communicable diseases (NCDs). Setting: The study was conducted in an urban township in Cape Town, South Africa. Method: A qualitative naturalistic research design utilising observations and in-depth interviews with CHWs and their supervisors working in Khayelitsha was used. Results: CHWs have multiple roles in the care of NCDs. They act as health educators, advisors, rehabilitation workers and support group facilitators. They further screen for complications of illness and assist community members to navigate the health system. These roles are shaped both by expectations of the health system and in response to community needs. CONCLUSION: This study indicates the complexities of the roles of CHWs working with NCDs. Understanding the actual roles of CHWs provides insights into not only the competencies required to enable them to fulfil their daily functions, but also the type of training required to fill the present gaps. Introduction Community health workers (CHWs) are increasingly being recognised as a crucial part of the health workforce.1 In South Africa and worldwide, CHWs have provided health care to communities for many decades and have assumed a variety of roles, including communityWeb of Scienc

Challenges facing successful scaling up of effective screening for cardiovascular disease by community health workers in Mexico and South Africa: Policy implications

The integration of community health workers (CHWs) into primary and secondary prevention functions in health programs and services delivery in Mexico and South Africa has been demonstrated to be effective. Task-sharing related to adherence and treatment, from nurses to CHWs, has also been effectively demonstrated in these areas. HIV/AIDS and TB programs in South Africa have seen similar successes in task-sharing with CHWs in the areas of screening for risk and adherence to treatment. In the area of non-communicable diseases (NCDs), there is a policy commitment to integrating CHWs into primary health care programs at public health facilities in both Mexico and South Africa in the areas of reproductive health and infant health. Yet current programs utilizing CHWs are not integrated into existing primary health care services in a comprehensive manner for primary and secondary prevention of NCDs. In a recently completed study, CHWs were trained to perform the basic diagnostic function of primary screening to assess the risk of suffering a CVD-related event in the community using a non-laboratory risk assessment tool and referring persons at moderate to high risk to local government clinics, for further assessment and management by a nurse or physician. In this paper we compare the experience with this CVD screening study to successful programs in vaccination, reproductive health, HIV/AIDS, and TB specifically to identify the barriers we identified as limitations to replicating these programs in the area of CVD diagnosis and management. We review barriers impacting the effective translation of policy into practice, including scale up issues; training and certification issues; integrating CHW to existing primary care teams and health system; funding and resource gaps. Finally, we suggest policy recommendations to replicate the demonstrated success of programs utilizing task-sharing with CHWs in infectious diseases and reproductive health, to integrated programs in NCD

Isothermal Crystallization Kinetics and Morphology of Double Crystalline PCL/PBS Blends Mixed with a Polycarbonate/MWCNTs Masterbatch

In this work, the 70/30 and 30/70 w/w polycaprolactone (PCL)/polybutylene succinate (PBS) blends and their corresponding PCL/PBS/(polycarbonate (PC)/multiwalled carbon nanotubes (MWCNTs) masterbatch) nanocomposites were prepared in a twin-screw extruder. The nanocomposites contained 1.0 and 4.0 wt% MWCNTs. The blends showed a sea-island morphology typical of immiscible blends. For the nanocomposites, three phases were formed: (i) The matrix (either PCL- or PBS-rich phase depending on the composition), (ii) dispersed polymer droplets of small size (either PCL- or PBS-rich phase depending on the composition), and (iii) dispersed aggregates of tens of micron sizes identified as PC/MWCNTs masterbatch. Atomic force microscopy (AFM) results showed that although most MWCNTs were located in the PC dispersed phase, some of them migrated to the polymer matrix. This is due to the partial miscibility and intimate contact at the interfaces between blend components. Non-isothermal differential scanning calorimetry (DSC) scans for the PCL/PBS blends showed an increase in the crystallization temperature (Tc) of the PCL-rich phase indicating a nucleation effect caused by the PBS-rich phase. For the nanocomposites, there was a decrease in Tc values. This was attributed to a competition between two effects: (1) The partial miscibility of the PC-rich and the PCL-rich and PBS-rich phases, and (2) the nucleation effect of the MWCNTs. The decrease in Tc values indicated that miscibility was the dominating effect. Isothermal crystallization results showed that the nanocomposites crystallized slower than the neat blends and the homopolymers. The introduction of the masterbatch generally increased the thermal conductivity of the blend nanocomposites and affected the mechanical properties.Thandi P. Gumede was financially supported by the National Research Foundation and the Sasol Inzalo Foundation in South Africa, while the POLYMAT/UPV/EHU team was funded by the following projects: “UPV/EHU Infrastructure: INF 14/38”; “Mineco/FEDER: SINF 130I001726XV1/Ref: UNPV13–4E–1726” and MINECO MAT2017-83014-C2-1-P. The publication of this article was funded by the Qatar National Library

Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a.

Macrophage galactose-type C-type lectins (MGLs), which were recently named CD301, have 2 homologues in mice: MGL1 and MGL2. MGLs are expressed on macrophages and immature dendritic cells. The persistent presence of granulation tissue induced by a protein antigen was observed in wild-type mice but not in mice lacking an endogenous, macrophage-specific, galactose-type calcium-type lectin 1 (MGL1) in an air pouch model. The anti-MGL1 antibody suppressed the granulation tissue formation in wild-type mice. A large number of cells, present only in the pouch of MGL1-deficient mice, were not myeloid or lymphoid lineage cells and the number significantly declined after administration of interleukin 1 alpha (IL-1alpha) into the pouch of MGL1-deficient mice. Furthermore, granulation tissue was restored by this treatment and the cells obtained from the pouch of MGL1-deficient mice were incorporated into the granulation tissue when injected with IL-1alpha. Taken together, MGL1 expressed on a specific subpopulation of macrophages that secrete IL-1alpha was proposed to regulate specific cellular interactions crucial to granulation tissue formation

Molecular Cloning and Characterization of a Novel Mouse Macrophage C-type Lectin, mMGL2, Which Has a Distinct Carbohydrate Specificity from mMGL1

A novel mouse macrophage galactose-type C-type lectin 2 (mMGL2) was identified by BLAST analysis of expressed sequence tags. The sequence of mMGL2 is highly homologous to the mMGL, which should now be called mMGL1. The open reading frame of mMGL2 contains a sequence corresponding to a type II transmembrane protein with 332 amino acids having a single extracellular C-type lectin domain. The 3\u27-untranslated region included long terminal repeats of mouse early transposon. The Mgl2 gene was cloned from a 129/SvJ mouse genomic library and sequenced. The gene spans 7,136 base pairs and consists of 10 exons, which is similar to the genomic organization of mMGL1. The reverse transcriptase-PCR analysis indicates that mMGL2 is expressed in cell lines and normal mouse tissues in a macrophage-restricted manner, also very similar to that of mMGL1. The mMGL2 mRNA was also detected in mMGL1-positive cells, which were sorted from thioglycollate-induced peritoneal cells with a mMGL1-specific monoclonal antibody, LOM-8.7. The soluble recombinant proteins of mMGL2 exhibited carbohydrate specificity for alpha- and beta-GalNAc-conjugated soluble polyacrylamides, whereas mMGL1 preferentially bound Lewis X-conjugated soluble polyacrylamides in solid phase assays. These two lectins may function cooperatively as recognition and endocytic molecules on macrophages and related cells

Isothermal Crystallization Kinetics and Morphology of Double Crystalline PCL/PBS Blends Mixed with a Polycarbonate/MWCNTs Masterbatch

Published ArticleIn this work, the 70/30 and 30/70 w/w polycaprolactone (PCL)/polybutylene succinate (PBS) blends and their corresponding PCL/PBS/(polycarbonate (PC)/multiwalled carbon nanotubes (MWCNTs) masterbatch) nanocomposites were prepared in a twin-screw extruder. The nanocomposites contained 1.0 and 4.0 wt% MWCNTs. The blends showed a sea-island morphology typical of immiscible blends. For the nanocomposites, three phases were formed: (i) The matrix (either PCL- or PBS-rich phase depending on the composition), (ii) dispersed polymer droplets of small size (either PCL- or PBS-rich phase depending on the composition), and (iii) dispersed aggregates of tens of micron sizes identified as PC/MWCNTs masterbatch. Atomic force microscopy (AFM) results showed that although most MWCNTs were located in the PC dispersed phase, some of them migrated to the polymer matrix. This is due to the partial miscibility and intimate contact at the interfaces between blend components. Non-isothermal di erential scanning calorimetry (DSC) scans for the PCL/PBS blends showed an increase in the crystallization temperature (Tc) of the PCL-rich phase indicating a nucleation e ect caused by the PBS-rich phase. For the nanocomposites, there was a decrease in Tc values. This was attributed to a competition between two e ects: (1) The partial miscibility of the PC-rich and the PCL-rich and PBS-rich phases, and (2) the nucleation e ect of the MWCNTs. The decrease in Tc values indicated that miscibility was the dominating e ect. Isothermal crystallization results showed that the nanocomposites crystallized slower than the neat blends and the homopolymers. The introduction of the masterbatch generally increased the thermal conductivity of the blend nanocomposites and a ected the mechanical properties

Demographic and socio-economic risk factors associated with self-reported TB

BACKGROUND : The infectiousness of Mycobacterium tuberculosis is known to be shaped by the human environment, with research showing positive associations with poverty, homelessness and overcrowding, among other factors. In this study, the focus is primarily on environmental health risks for TB, particularly on those associated with sociodemographic and household living conditions in South Africa. METHODS : Data for this study were collected between 2014 and 2019 from a number of sites implementing community-oriented primary care (COPC) in the Gauteng Province of the country. Community health workers (CHWs) used AitaHealthtm, a custom-built mobile information management application, to obtain data on the TB status and environmental conditions of households. Statistical models were used to determine associations between various demographic, socio-economic and environmental risk factors, and TB. RESULTS : Approximately 12,503 TB cases were reported among 7,769 households. Substance use and male-headed households were found to have significant associations in households with at least one individual with TB. Overcrowding, as well as lack of access to piped water and adequate sanitation were also found to be positively associated with a 'TB-household. CONCLUSION : Improvements in housing and services, particularly the provision of piped water and reticulated flush toilets, are needed to control and prevent TB in South Africa.https://theunion.org/our-work/journals/ijtldhj2023Family MedicineGeography, Geoinformatics and Meteorolog

Cost-effectiveness of Lifestyle Africa: an adaptation of the diabetes prevention programme for delivery by community health workers in urban South Africa

Background Lifestyle Africa is an adapted version of the Diabetes Prevention Program designed for delivery by community health workers to socioeconomically disadvantaged populations in low- and middle-income countries (LMICs). Results from the Lifestyle Africa trial conducted in an under-resourced community in South Africa indicated that the programme had a significant effect on reducing haemoglobin A1c (HbA1c). Objective To estimate the cost of implementation and the cost-effectiveness (in cost per point reduction in HbA1c) of the Lifestyle Africa programme to inform decision-makers of the resources required and the value of this intervention. Methods Interviews were held with project administrators to identify the activities and resources required to implement the intervention. A direct-measure micro-costing approach was used to determine the number of units and unit cost for each resource. The incremental cost per one point improvement in HbA1c was calculated. Results The intervention equated to 71 United States dollars (USD) in implementation costs per participant and a 0.26 improvement in HbA1c per participant. Conclusions Lifestyle Africa reduced HbA1c for relatively little cost and holds promise for addressing chronic disease in LMIC. Decision-makers should consider the comparative clinical effectiveness and cost-effectiveness of this intervention when making resource allocation decisions

Ethics of Engagement and Insider-Outsider Perspectives: Issues and Dilemmas in Cross-Cultural Interpretation

This article offers insights into the ethics of engagement and methodological issues and dilemmas in cross-cultural interpretation for researchers who are positioned at different points of the insider-outsider spectrum. The discussion uses examples from qualitative research with Sikh families in Britain and focuses on the design of the methodology and co-interpretation of data from in-depth interviews, both during the interactive data gathering phase and the post-interview analysis and interpretation phase. The researchers represent differing degrees of insider-outsiderness in relation to the British Sikh community; one is a cultural insider (a Sikh) whilst the other is an outsider (non-Sikh). In other respects they share a number of characteristics, including gender, a history of migration, bilingualism and living and teaching in superdiverse communities which all impact on the nature of their engagement with the research participants and with each other as co-researchers. Our reflexive analysis shows that established binary distinctions and polarities in research practice, such as insider/outsider, are inadequate for conceptualising the fluidity and complexity of the ethics of engagement in co-researching. We argue that both theoretically and empirically a more nuanced conceptualisation reflects the realities of multiple researcher positionalities, interpretations and power relations