Genetic variability in a population of Letelle sheep in South Africa

The purpose of the study was to gain insight into the genetic variability of the Letelle sheep breed, a breed that has been managed as a closed population for 90 years, with no new genetic material being permitted into the breed. The Letelle is a South African developed dual-purpose sheep breed and is classified as a Merino type with a Spanish Merino origin. The breed exhibits good fine wool characteristics and yields high-quality mutton. Line-breeding, family-breeding, and inbreeding are applied, and multiple sire matings are practised to prevent a sire from having a large influence on the national flock. Ear samples were collected from 10 animals each from 10 commercial and 11 seed-stock flocks and genotyped using 17 microsatellite markers. Unbiased heterozygosity ranged from 0.58 to 0.68 and the observed heterozygosity from 0.52 to 0.65. The estimated effective population size (Ne) was 228.2 - 321.9. Results from analysis of molecular variance (AMOVA), a Bayesian assignment test, and a neighbour-joining (NJ) tree suggested that no genetic sub-structure existed within this population and that the seed-stock and commercial flocks could be regarded as one genetic population. The average within flock (FIS) and within breed (FIT) inbreeding coefficients were 10.1% and 14.5%, respectively. Despite the level of inbreeding, levels of genetic diversity were moderate and potentially provide opportunities for future selection and adaptation. Further testing could identify flocks in which conservation management is required as well as those with high genetic variability, which would provide the best reservoir for selection to adapt to future climatic challenges.Keywords: genetic distance, inbreeding, microsatellite markers, population structur

Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency

Background Isolated complex II deficiency is a rare form of mitochondrial disease, accounting for approximately 2% of all respiratory chain deficiency diagnoses. The succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC and SDHD) are autosomally-encoded and transcribe the conjugated heterotetramers of complex II via the action of two known assembly factors (SDHAF1 and SDHAF2). Only a handful of reports describe inherited SDH gene defects as a cause of paediatric mitochondrial disease, involving either SDHA (Leigh syndrome, cardiomyopathy) or SDHAF1 (infantile leukoencephalopathy). However, all four SDH genes, together with SDHAF2, have known tumour suppressor functions, with numerous germline and somatic mutations reported in association with hereditary cancer syndromes, including paraganglioma and pheochromocytoma. Methods and results Here, we report the clinical and molecular investigations of two patients with histochemical and biochemical evidence of a severe, isolated complex II deficiency due to novel SDH gene mutations; the first patient presented with cardiomyopathy and leukodystrophy due to compound heterozygous p.Thr508Ile and p.Ser509Leu SDHA mutations, while the second patient presented with hypotonia and leukodystrophy with elevated brain succinate demonstrated by MR spectroscopy due to a novel, homozygous p.Asp48Val SDHB mutation. Western blotting and BN-PAGE studies confirmed decreased steady-state levels of the relevant SDH subunits and impairment of complex II assembly. Evidence from yeast complementation studies provided additional support for pathogenicity of the SDHB mutation. Conclusions Our report represents the first example of SDHB mutation as a cause of inherited mitochondrial respiratory chain disease and extends the SDHA mutation spectrum in patients with isolated complex II deficiency

A multicentre crosssectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province South Africa

Background. Hypertension is common, affecting over one billion people worldwide. In sub-Saharan Africa, hypertensive disease not only affects the older population but is becoming increasingly prevalent in younger individuals. In South Africa (SA), >30% of the adult population has hypertension, making it the single most common cardiovascular risk factor and the predominant contributor to cardiovascular disease and mortality. Elevated blood pressure is the most common perioperative comorbidity encountered in non-cardiac surgical patients, with an overall prevalence of 20 - 25%, and it remains poorly controlled in low- and middle-income countries. Hypertension in the perioperative setting may adversely affect patient outcome. It therefore not only flags possible perioperative challenges to anaesthesiologists, but also identifies patients at risk of long-term morbidity and mortality.Objectives. To determine the prevalence and severity of hypertension in elective adult surgical patients in the Western Cape Province, SA.Results. The study population included all elective surgical patients from seven hospitals in the Western Cape during a 1-week period. Hypertension, defined as having had a previous diagnosis of hypertension or meeting the blood pressure criteria of >140/90 mmHg, was identified in 51.8% of patients during preoperative assessment. Significantly, newly diagnosed hypertension was present in 9.9% of all patients presenting for elective surgery. Although 98.1% of the known hypertensive patients were on antihypertensive therapy, 36.9% were inadequately controlled. There are numerous reasons for this, but notably 32.1% of patients admitted to forgetting to take their medication, making patient factors the most common reason for treatment non-compliance.Conclusions. The perioperative period may be an important opportunity to identify undiagnosed hypertensive patients. The perioperative encounter may have a significant public health implication in facilitating appropriate referral and treatment of patients with hypertension to decrease long-term cardiovascular complications in SA.Â

Field observations on the natural history and breeding behavior of the Atacama toad (Rhinella atacamensis, Anura: Bufonidae) from Chile

Amphibians have diversified predominantly across tropical environments where humidity, temperature and microhabitat availability facilitate demographic stability. However, a number of lineages have colonized extreme deserts, where their diversities are considerably lower. One species in particular, the Atacama toad (Rhinella atacamensis), has adapted to the Atacama Desert, the driest place on Earth. Despite the ecological uniqueness of this species, most aspects of its natural history, reproduction, patterns of activity and behavior remain unknown. Using camera traps and in situ field observations, we report a set of novel natural history findings in a population from the Llanos de Challe National Park. We show that R. atacamensis remains hidden from the sun in small pools under vegetation, where 100% of observed femalJes have a male permanently attached in amplexus at all times. The toads emerge to gather in small ponds after the sunset (~20:00h), where males engage in active contests over females, with up to four males competing for one female. They retreat into the covered pools after ~06:00h. Eggs laid during the night hatch within 24 hours. We discuss these observations in the context of the global diversity of bufonid toads in general, and in relation with the effects that selection emerging from the harsh conditions of Atacama may exert on the expression of these traits

Expanding the Social Security Net in South Africa: Opportunities, Challenges and Constraints

Rapid increases in government expenditure on social security between 2000 and 2006 has further increased poor households’ reliance on welfare grants and has been important in the fight against poverty. Already there is evidence of a substitution taking place within the social budget: expenditure on education and health seems to have declined in favour of increased welfare transfer expenditure

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study

Background A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. Methods Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. Results Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. Conclusion The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs

Molecular basis of association of receptor activity-modifying protein 3 with the family B G protein-coupled secretin receptor

The three receptor activity-modifying proteins (RAMPs) have been recognized as being important for the trafficking and function of a subset of family B G protein-coupled receptors, although the structural basis for this has not been well established. In the current work, we use morphological fluorescence techniques, bioluminescence resonance energy transfer, and bimolecular fluorescence complementation to demonstrate that the secretin receptor associates specifically with RAMP3, but not with RAMP1 or RAMP2. We use truncation constructs, peptide competition experiments, and chimeric secretin-GLP1 receptor constructs to establish that this association is structurally specific, dependent on the intramembranous region of the RAMP and TM6 and TM7 of this receptor. There were no observed changes in secretin-stimulated cAMP, intracellular calcium, ERK1/2 phosphorylation, or receptor internalization in receptor-bearing COS or CHO-K1 cells in the presence or absence of exogenous RAMP transfection, although the secretin receptor trafficks normally to the cell surface in these cells in a RAMP-independent manner, resulting in both free and RAMP-associated receptor on the cell surface. RAMP3 association with this receptor was shown to be capable of rescuing a receptor mutant (G241C) that is normally trapped intracellularly in the biosynthetic machinery. Similarly, secretin receptor expression had functional effects on adrenomedullin activity, with increasing secretin receptor expression competing for RAMP3 association with the calcitonin receptor-like receptor to yield a functional adrenomedullin receptor. These data provide important new insights into the structural basis for RAMP3 interaction with a family B G protein-coupled receptor, potentially providing a highly selective target for drug action. This may be representative of similar interactions between other members of this receptor family and RAMP proteins