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

From Liberation Movements to Ruling Parties: How useful are Dominant Party System frameworks in explaining Southern African former National Liberation Movements?

Both within academic and contemporary circles, the nascent nature of the South African democracy cannot be denied. Although many may illustrate the massive strides made within the South African democratic project, it is by no means a ‘consolidated democracy’ with its greatest test yet still ahead: The transition of power away from the ruling liberation party, the African National Congress. While many African states, both within Southern Africa and across the continent at large, have suffered massive political, economic, social, and humanitarian crises subsequent to liberation, South Africa has largely escaped such calamities. However, it can be argued that the continued avoidance of similar calamities rests upon the continued maturation of the South African democracy. Although many scholars have written about democratic consolidation from sociological, economic, and broadly political positions globally, Southern Africa is unique due to the presence and concentration of liberation movements turned ruling parties. Due to their respective histories of opposing the rule of colonial governments, or white minority regimes, these ‘liberation parties’ ascend to power with a vast amount of popular support, and in turn legitimacy, leading to the erection of dominant party structures. Despite possessing strong political, economic and moral mandates, these liberation movements have subjected their electorates to massive service delivery failures, and in many instances autocratic behavior, hindering, irreparably damaging, or completely reversing the democratic advances made. As such, it is vital to not only evaluate the post liberation ability of formerly liberation movements, but also to critically examine the nature of these liberation parties, and their effect on the advancement of democratic principles, this paper intends to focus on the latter

The universtiy in a developing free society : challenges to autonomy and academic freedom

The real point of democratic reform, what I have been calling institutional reform, is not just to change the complexion of researchers, teachers and students, nor just to change the location of research and teaching, to be truly meaning- fill, reform has to lead to a change in the orientation of these activities. Let me take a hypothetical example, one where you succeed in adding more black and female faces to the research and leaching establishment and even to shifting the location of that establishment mainly to historically black universities - say your most advanced medical research facilities come to be located at the University of Fort Hare, with researchers mainly black and female, but the facility is still oriented to proton beam research for special types of cancer, away from the public health needs of the people - what will you have achieved? I dare say you would then have joined the ranks of independent Africa. The key issue will still remain not addressed: who should centres of research and learning serve and how? This is why I think the real challenge for all of us, whether south or north of the Limpopo, whether black or brown, yellow or white, is to begin thinking of how to root African universities in African soil

Critically Analyzing Biko’s Views on Race & Racism

Drawing from the work of Mabogo More, this paper will attempt to present a comprehensive analysis of Steve Biko’s views on race and racism. The analysis will commence by reviewing and outlining the broad philosophical schools of thought regarding the conceptualization of race, and it’s relevance within society, namely; Racial Naturalism, Racial Nihilism or Skepticism, and Racial Constructivism. Subsequently, this paper will attempt to locate More’s interpretation of Biko’s views as being constructivist, despite the prevalence of non-racial, skeptical conceptions within contemporary South Africa. In light of these skeptical conceptions, this paper will apply Biko’s philosophical views to specifically answer the following questions: Firstly, Can black people be racist? Secondly, Could racism ever go out of existence? Finally, this paper will address the question: Could race ever cease to exist

Mortality analysis of people with severe mental illness transferred from longstay hospital to alternative care in the Life Esidimeni tragedy

A mortality analysis of the Life Esidimeni tragedy was precluded during the investigation by the Health Ombud by the lack of data integrity. Information on the mental healthcare users (MHCUs) transferred out of Life Esidimeni hospitals between October 2015 and June 2016 was subsequently collected by the Gauteng Department of Health, permitting statistical analysis. Survival rates were calculated according to gender and transfer destination and adjusted for patient age. Mortality was compared with that of the general population for the calendar year of 2016. Of the 1 442 MHCUs, 15% were transferred to specialised psychiatric hospitals and 85% to a rehabilitation centre or non-governmental residential facility. By the end of August 2017, 9% (n=131) of the cohort had died. Significant predictors of survival were younger age (p<0.0001) and transfer to a psychiatric institution (p=0.004). The age-adjusted death rate was 63/1 000 and the overall standardised mortality ratio (SMR) was 4.9 (95% confidence interval (CI) 3.92 - 5.80), with an SMR of 3.9 (95% CI 2.95 - 4.86) for men and 6.3 (95% CI 4.22 - 8.38) for women. The excess deaths are therefore quantified, and the high-risk environment of the rehabilitation centre and residential facilities confirmed. High mortality among MHCUs is unlikely to be confined to the Life Esidimeni tragedy; monitoring of preventable deaths in this vulnerable population is recommended

First-Trimester Circulating 25-Hydroxyvitamin D Levels and Development of Gestational Diabetes Mellitus

OBJECTIVE-To investigate the association between first-trimester maternal serum levels of 25-hydroxyvitamin D (25-OH-D) as measured by liquid chromatography-tandem mass spectrometry and development of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS-We conducted a case-control study involving 248 women in the first-trimester of pregnancy, 90 of whom developed GDM and 158 remained normoglycemic. RESULTS-Although booking 25-OH-D levels correlated negatively with 2-h glucose postoral glucose tolerance test and positively with HDL cholesterol, as well as with ethnicity, obesity, and smoking (all P < 0.05), there were no statistically significant differences in baseline maternal mean 25-OH-D levels between those who subsequently developed GDM, 18.9 ng/mL (SD 10.7) and those who remained normoglycemic, 19.0 ng/mL (10.7) (P = 0.874), even after adjustment for possible confounders including sampling month (P = 0.784). CONCLUSIONS-Our large and well-phenotyped prospective study did not find evidence of an association between first-trimester maternal levels of 25-OH-D and subsequent development of GDM

First-Trimester Prediction of Gestational Diabetes Mellitus: Examining the Potential of Combining Maternal Characteristics and Laboratory Measures

OBJECTIVE Predictors of gestational diabetes mellitus (GDM) have been widely studied, but few studies have considered multiple measures. Our objective was to integrate several potential GDM predictors with consideration to both simple and novel measures and to determine the extent to which GDM can be predicted in the first trimester. RESEARCH DESIGN AND METHODS We identified first-trimester maternal samples from 124 women who developed GDM and 248 control subjects who did not. We gathered data on age, BMI, parity, race, smoking, prior GDM, family history of diabetes, and blood pressure. Using retrieved samples, we measured routine (lipids, high-sensitivity C-reactive protein, and gamma-glutamyltransferase) and novel (adiponectin, E-selectin, and tissue plasminogen activator [t-PA]) parameters. We determined independent predictors from stepwise regression analyses, calculated areas under the receiver-operating characteristic curves (AUC-ROC), and integrated discrimination improvement (IDI) for relevant models. RESULTS Compared with control subjects, women who subsequently developed GDM were older, had higher BMIs, were more likely to be of Asian origin, had a history of GDM or family history of type 2 diabetes, and had higher systolic blood pressure (P < 0.05 for all). With regard biochemical measures, stepwise analyses identified only elevated t-PA and low HDL cholesterol levels as significant (P <= 0.015) independent predictors of GDM beyond simple non-laboratory-based maternal measures. Their inclusion improved the AUC-ROC from 0.824 to 0.861 and IDI by 0.052 (0.017-0.115). CONCLUSIONS GDM can be usefully estimated from a mix of simple questions with potential for further improvement by specific blood measures (lipids and t-PA)

Data and Safety Monitoring of COVID-19 Vaccine Clinical Trials

To speed the development of vaccines against SARS-CoV-2, the United States Federal Government has funded multiple phase 3 trials of candidate vaccines. A single 11-member data and safety monitoring board (DSMB) monitors all government-funded trials to ensure coordinated oversight, promote harmonized designs, and allow shared insights related to safety across trials. DSMB reviews encompass 3 domains: (1) the conduct of trials, including overall and subgroup accrual and data quality and completeness; (2) safety, including individual events of concern and comparisons by randomized group; and (3) interim analyses of efficacy when event-driven milestones are met. Challenges have included the scale and pace of the trials, the frequency of safety events related to the combined enrollment of over 100 000 participants, many of whom are older adults or have comorbid conditions that place them at independent risk of serious health events, and the politicized environment in which the trials have taken place