The South African Medical Research Council

The statutory function of control over all matters concerning medical, dental and related biological and physical research, as contained in the Act of the South African Medical Research Council No. 19 of 1969, are set out. The various research activities, administrative procedures and policies, are outlined. Special attention is drawn to the 2 institutes, viz. the National Research Institute for Occupational Diseases (NRIOD) and the National Research Institute for Nutritional Diseases (NRIND), to the 25 research units and groups, and the increasing number of individual project researchers. Allocation of funds is based on the policy that research is supported where it can best be pursued.S. Afr. Med. J., 48, 1325 (1974)

Use of vaccines as a key antimicrobial stewardship strategy

Vaccination may prevent bacterial infections and decrease the potential for transmission. Some effective vaccines may reduce bacterial colonisation and exposure to antimicrobials by minimising the spread of  resistant strains; in this regard, a substantial indirect immunity has been demonstrated that protects unvaccinated members of society. One of the best documented examples of the crucial role of vaccination has been an adjunct to an antimicrobial stewardship programme. Pneumococcal conjugate vaccines (PCVs), for example, target the most virulent pneumococcal serotypes, which are linked to invasive disease and associated with antibiotic resistance. In this regard, recent local data highlight the remarkable impact of the sequential introduction of 7- and 13-valent PCV (PCV7/PCV13) on the incidence of penicillin-, ceftriaxone- and multidrug-resistant pneumococcal infections in South Africa in only 4 years. Equally impressive have been vaccines  directed towards viruses such as influenza, which also have direct and indirect effects on antibiotic consumption

Optimising the administration of antibiotics in critically ill patients

Optimal outcome and a reduction in the potential for resistance require that appropriate pharmacokinetic (PK) targets are achieved. Consequently, we need to target drug concentrations that are significantly  higher than those conventionally presumed to be adequate. Drug exposure varies according to the  molecular weight, degree of ionisation, protein binding and lipid solubility of each agent. In critically ill patients,  hypoalbuminaemia increases the free fraction of hydrophilic drugs, which in turn increases the volume of distribution and clearance (CL), both of which result in reduced drug levels. Similarly, augmented renal clearance (ARC), defined as a creatinine clearance (CLcr) of >130 mL/min/1.73 m2, which occurs frequently in critically ill patients, particularly younger patients with normal or near-normal creatinine levels, may also significantly reduce drug exposure. Studies have demonstrated a greater mortality and lower cure with ARC, particularly with the additive effects of obesity, hypoalbuminaemia and increasing resistance, if conventional dosages are used. These concepts apply to antibiotics targeting Gram-negative and -positive organisms. Knowledge of PK and the resistance profiles of organisms in each environment is necessary to prescribe appropriately. This article discusses these issues and the doses that should be used

Computerised Analysis, Interpretation, Storage and Retrieval of Electrocardiograms

A study was undertaken to determine the feasibility of introducing a computerised electrocardiographic analysis and interpretive system as a service to a teaching and referral hospital. Available computer equipment and programmes are considered. The accuracy and quality of the analysis and interpretation of the electrocardiographic contours are basically dependent on such factors as pattern recognition, the criteria adopted for determining abnormalities, the relative values placed on scalar and orthogonal leads and the role of review by the physician. It is concluded that such systems are at a stage where they can feasibly be introduced and should be of advantage in freeing the physician from ,routine measuring and screening of electrocardiograms, thus saving many hours of professional and academic time. Furthermore, such systems can contribute greatly as an educational tool and increase the general knowledge of electrocardiography. Systems for storage and retrieval are also being developed and becoming available. The whole field is a developing one and continuous updating of programmes by the addition of more data, particularly for children, and the introduction of electrocardiographic comparison programmes need to be expedited.S. Afr. Med. J., 48, 1141 (1974)

OXA β-lactamases

The OXA β-lactamases were among the earliest β-lactamases detected; however, these molecular class D β-lactamases were originally relatively rare and always plasmid mediated. They had a substrate profile limited to the penicillins, but some became able to confer resistance to cephalosporins. From the 1980s onwards, isolates of Acinetobacter baumannii that were resistant to the carbapenems emerged, manifested by plasmid-encoded β-lactamases (OXA-23, OXA-40, and OXA-58) categorized as OXA enzymes because of their sequence similarity to earlier OXA β-lactamases. It was soon found that every A. baumannii strain possessed a chromosomally encoded OXA β-lactamase (OXA-51-like), some of which could confer resistance to carbapenems when the genetic environment around the gene promoted its expression. Similarly, Acinetobacter species closely related to A. baumannii also possessed their own chromosomally encoded OXA β-lactamases; some could be transferred to A. baumannii, and they formed the basis of transferable carbapenem resistance in this species. In some cases, the carbapenem-resistant OXA β-lactamases (OXA-48) have migrated into the Enterobacteriaceae and are becoming a significant cause of carbapenem resistance. The emergence of OXA enzymes that can confer resistance to carbapenems, particularly in A. baumannii, has transformed these β-lactamases from a minor hindrance into a major problem set to demote the clinical efficacy of the carbapenems

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome

Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our countr

Recovery and performance in sport: Consensus statement

© 2018 Human Kinetics, Inc. The relationship between recovery and fatigue and its impact on performance has attracted the interest of sport science for many years. An adequate balance between stress (training and competition load, other life demands) and recovery is essential for athletes to achieve continuous high-level performance. Research has focused on the examination of physiological and psychological recovery strategies to compensate external and internal training and competition loads. A systematic monitoring of recovery and the subsequent implementation of recovery routines aims at maximizing performance and preventing negative developments such as underrecovery, nonfunctional overreaching, the overtraining syndrome, injuries, or illnesses. Due to the inter- and intraindividual variability of responses to training, competition, and recovery strategies, a diverse set of expertise is required to address the multifaceted phenomena of recovery, performance, and their interactions to transfer knowledge from sport science to sport practice. For this purpose, a symposium on Recovery and Performance was organized at the Technical University Munich Science and Study Center Raitenhaslach (Germany) in September 2016. Various international experts from many disciplines and research areas gathered to discuss and share their knowledge of recovery for performance enhancement in a variety of settings. The results of this meeting are outlined in this consensus statement that provides central definitions, theoretical frameworks, and practical implications as a synopsis of the current knowledge of recovery and performance. While our understanding of the complex relationship between recovery and performance has significantly increased through research, some important issues for future investigations are also elaborated

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Sampling and contaminant monitoring protocol for raptors

In May 2013 representatives from six countries gathered in Murcia, Spain, to attend the Workshop on &ldquo;Setting best practices on raptor contaminant monitoring activities in Europe&rdquo; funded by EURAPMON. The workshop developed a rough draft of the current protocol. The protocol was subsequently completed with the involvement of investigators from Belgium, Denmark, France, Germany, The Netherlands, Norway, Spain, Sweden and the United Kingdom. All contributors are experts in monitoring contaminants in raptors. The aim of this sampling protocol is to provide guidance on types of best practice that will facilitate harmonisation of procedures between existing and emerging schemes and so maximise the reliability, comparability and interoperability of data.The methods here do not require use of anaesthesia on birds. This protocol covers the sampling of blood and feathers from live birds, addled and deserted eggs, internal organs and tissues from dead specimens, and other samples such as faeces, preen oil and pellets.</p