Molecular mechanisms of insulin resistance

This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin resistance could ultimately lead to a better understanding of the causation of these conditions and the design of rational therapy to ameliorate them. Here, particular attention is devoted to the initial events that follow the binding of insulin to its receptor, including changes in insulin receptor phosphorylation. Receptor-mediated insulin resistance may be a consequence of various factors including increased serine/threonine phosphorylation of the receptor with decreased tyrosine phosphorylation, receptor densitisation, auto-antibodies to the receptor and inherited structural defects in the insulin receptor. Defects in insulin action could also arise at post-receptor events particularly glucose transport. Other circulating hormones, such as the newly characterised islet amyloid polypeptide (amylin), may also cause insulin resistance

Considering the role of social media: #BlackLivesMatter as a pedagogical intervention to decolonise curriculum

The COVID-19 pandemic resulted in a drastic transformation to schooling for students throughout the world. During this period, a number of issues arose in our local, national and global communities, including the death of George Floyd and subsequent protests and rallies organised by #BlackLivesMatter. Living through and witnessing many social issues, coupled with the new and enduring pandemic, furthered our understandings of how young people were engaging with these topics without the structures of schools to support them. This article presents the results of a case study where youth aged 15–17 years shared their experiences and understandings about many social justice issues they were observing. The most significant learning around these issues for youth occurred informally through social media as opposed to in the classroom, reinforcing that schools are not ethical spaces from which to challenge institutional, structural and systemic barriers to justice. As such, this article discusses the potential for formal education to be transformed into an ethical and decolonising space to learn about and challenge injustice

Inadequacy of primary health care test request guidelines - lack of evidence base

Evidence suggests that 3 - 4% of patient encounters in primary health care result in blood tests being requested. There is compelling evidence of significant misuse and poor utilisation of many laboratory tests, which results in an economic burden and other problems including further investigation of false-positive results. Patients have high expectations that blood tests be performed and have little understanding of the limitations of testing. The frequency of test ordering is much higher in the USA and Canada, for example, than in the UK, without any overt difference in the quality of care. There are suggestions that 30 - 50% of tests are unnecessary, and that about 15% of abnormal results are not acted upon

Inadequacy of primary health care test request guidelines - lack of evidence base

Evidence suggests that 3 - 4% of patient encounters in primary health care result in blood tests being requested. There is compelling evidence of significant misuse and poor utilisation of many laboratory tests, which results in an economic burden and other problems including further investigation of false-positive results. Patients have high expectations that blood tests be performed and have little understanding of the limitations of testing. The frequency of test ordering is much higher in the USA and Canada, for example, than in the UK, without any overt difference in the quality of care. There are suggestions that 30 - 50% of tests are unnecessary, and that about 15% of abnormal results are not acted upon

Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms

The increase in incidence of HIV infection continues to be a major public health problem across the world, but more especially in sub-Saharan Africa. Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients with AIDS, but it has also increased the incidence of various metabolic disorders, in particular insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often accompanied by frank type 2 diabetes and increased mortality from cardiovascular disease. It is important to understand the mechanistic basis for these side-effects as the incidence of these is likely to increase as the rollout of antiretroviral drugs continues

Analysis of Dominant HIV Quasispecies Suggests Independent Viral Evolution Within Spinal Granulomas Coinfected with Mycobacterium tuberculosis and HIV-1 Subtype C

Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide, largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified, and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1 clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of putative N-linked glycosylation sites in both compartments. CD68(+) reactivity was associated with higher tissue viral load (r = 1.0; p < 0.01) but not greater intrapatient diversity (r = 0.60; p > 0.05). Ultrastructural imaging revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution. Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the process of viral sequestration within this compartment

Kwazulu-Natal minibus taxi drivers’ perceptions on HIV and AIDS: Transmission, prevention, support and effects on the industry

In South Africa, the minibus taxi drivers are largely becoming another high-risk category in the HIV and AIDS epidemic. Although previous studies have shown that knowledge of HIV and AIDS is relatively high among the taxi drivers it is still not clear how this sub-population perceive the support rendered to them with regard to HIV and AIDS prevention strategies. This study aimed to focus on this atypical workplace and explore the KwaZulu-Natal, minibus taxi drivers’ perceptions on HIV and AIDS. In this study, qualitative methods were utilized to determine the minibus taxi drivers’ understanding of HIV and AIDS infection, HIV prevention strategies, existing support strategies and effects of HIV and AIDS on the taxi industry. Focus-group discussions were conducted, to collect data. The results showed that even though the taxi drivers had some understanding on HIV and AIDS there was still a dire need for interventions that were geared towards addressing HIV-related needs of the drivers in this industr

Developing an early life Parent Education Programme in response to high infant mortality rates

This is an accepted manuscript of an article published by Elsevier in Journal of Neonatal Nursing on 16/03/2017, available online: https://doi.org/10.1016/j.jnn.2017.02.005 The accepted version of the publication may differ from the final published version.Published versio

New imaging approaches for improving diagnosis of childhood tuberculosis

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