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Collins M.,University of Cape Town | Collins M.,South African Medical Research Council | Posthumus M.,University of Cape Town
Exercise and Sport Sciences Reviews | Year: 2011

We have shown that a variant within COL5A1, which encodes a subunit of type V collagen, is associated with injury and performance phenotypes. Although seemingly unrelated, these phenotypes are associated directly or indirectly with the mechanical properties of musculoskeletal soft tissue. We therefore hypothesize that variants in the COL5A1 gene alter fibril architecture and structure and, thereby, mechanical properties. © 2011 by the American College of Sports Medicine. Source


Echouffo-Tcheugui J.B.,Emory University | Kengne A.P.,South African Medical Research Council | Kengne A.P.,University of Cape Town | Kengne A.P.,The George Institute for Global Health | Kengne A.P.,University Utrecht
PLoS Medicine | Year: 2012

Background: Chronic kidney disease (CKD) is common, and associated with increased risk of cardiovascular disease and end-stage renal disease, which are potentially preventable through early identification and treatment of individuals at risk. Although risk factors for occurrence and progression of CKD have been identified, their utility for CKD risk stratification through prediction models remains unclear. We critically assessed risk models to predict CKD and its progression, and evaluated their suitability for clinical use. Methods and Findings: We systematically searched MEDLINE and Embase (1 January 1980 to 20 June 2012). Dual review was conducted to identify studies that reported on the development, validation, or impact assessment of a model constructed to predict the occurrence/presence of CKD or progression to advanced stages. Data were extracted on study characteristics, risk predictors, discrimination, calibration, and reclassification performance of models, as well as validation and impact analyses. We included 26 publications reporting on 30 CKD occurrence prediction risk scores and 17 CKD progression prediction risk scores. The vast majority of CKD risk models had acceptable-to-good discriminatory performance (area under the receiver operating characteristic curve>0.70) in the derivation sample. Calibration was less commonly assessed, but overall was found to be acceptable. Only eight CKD occurrence and five CKD progression risk models have been externally validated, displaying modest-to-acceptable discrimination. Whether novel biomarkers of CKD (circulatory or genetic) can improve prediction largely remains unclear, and impact studies of CKD prediction models have not yet been conducted. Limitations of risk models include the lack of ethnic diversity in derivation samples, and the scarcity of validation studies. The review is limited by the lack of an agreed-on system for rating prediction models, and the difficulty of assessing publication bias. Conclusions: The development and clinical application of renal risk scores is in its infancy; however, the discriminatory performance of existing tools is acceptable. The effect of using these models in practice is still to be explored. Please see later in the article for the Editors' Summary. © 2012 Echouffo-Tcheugui, Kengne. Source


Cerf M.E.,South African Medical Research Council
Frontiers in Endocrinology | Year: 2013

Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis. © 2013 Cerf. Source


Cerf M.E.,South African Medical Research Council
Cell Biology International | Year: 2011

The pancreas is characterized by a major component, an exocrine and ductal system involved in digestion, and a minor component, the endocrine islets represented by islet micro-organs that tightly regulate glucose homoeostasis. Pancreatic organogenesis is strictly co-ordinated by transcription factors that are expressed sequentially to yield functional islets capable of maintaining glucose homoeostasis. Angiogenesis and innervation complete islet development, equipping islets to respond to metabolic demands. Proper regulation of this triad of processes during development is critical for establishing functional islets. © 2011 Portland Press Limited. Source


Allanson E.R.,University of Western Australia | Pattinson R.C.,South African Medical Research Council
Bulletin of the World Health Organization | Year: 2015

Problem Suboptimal care contributes to perinatal mortality rates. Quality-of-care audits can be used to identify and change suboptimal care, but it is not known if such audits have reduced perinatal mortality in South Africa. Approach We investigated perinatal mortality trends in health facilities that had completed at least five years of quality-of-care audits. In a subset of facilities that began audits from 2006, we analysed modifiable factors that may have contributed to perinatal deaths. Local setting Since the 1990s, the perinatal problem identification programme has performed quality-of-care audits in South Africa to record perinatal deaths, identify modifiable factors and motivate change. Relevant changes Five years of continuous audits were available for 163 facilities. Perinatal mortality rates decreased in 48 facilities (29%) and increased in 52 (32%). Among the subset of facilities that began audits in 2006, there was a decrease in perinatal mortality of 30% (16/54) but an increase in 35% (19/54). Facilities with increasing perinatal mortality were more likely to identify the following contributing factors: patient delay in seeking help when a baby was ill (odds ratio, OR: 4.67; 95% confidence interval, CI: 1.99–10.97); lack of use of antenatal steroids (OR: 9.57; 95% CI: 2.97–30.81); lack of nursing personnel (OR: 2.67; 95% CI: 1.34–5.33); fetal distress not detected antepartum when the fetus is monitored (OR: 2.92; 95% CI: 1.47–5.8) and poor progress in labour with incorrect interpretation of the partogram (OR: 2.77; 95% CI: 1.43–5.34). Lessons learnt Quality-of-care audits were not shown to improve perinatal mortality in this study. © 2015, World Health Organization. All Rights Reserved. Source

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