A new find of Megalotragus priscus (Alcelaphini, Bovidae) from the central Karoo, South Africa

Main articleWe document the occurrence of the Florisian, or late Quaternary, form of the giant alcelaphine, Megalotragus priscus, from dongas on the Ongers River, near Britstown in the central Karoo. This is significant as it confirms the occurrence of the species in the Karoo and it suggests significantly wetter environments and productive grasslands in the central Karoo in pre-Holocene times. The present-day Karoo environment did not maintain populations of large ruminant grazers similar to M. priscus, and other specialized Florisian grazers, prior to the advent of agriculture and pasture management. Aridification in recent times is the likely cause of changes in grassland quality and the local dissappearance of these animals, if not their extinction.Non

Problems experienced by secondary school deputy principals in diverse contexts: a South African study

This paper reports on research that was undertaken to determine the problems experienced by deputy principals in secondary schools, and the extent to which these problems were experienced. Although some research was conducted on the deputy principalship, no research treats the problems that deputy principals experience upon appointment comprehensively. An understanding of the problems experienced by secondary school deputy principals is a necessary precursor of an induction program to address the problems. A quantitative approach which was underpinned by the post-positivist paradigm was adopted. In order to determine the extent to which the problems were experienced, a survey was conducted among one hundred and fifty seven secondary school deputy principals in the North West Province. The participants came from a diverse context of rural, township and urban schools. The deputy principals who participated in the study included those who were newly appointed (one to three years of service) and those who were experienced (more than three years of service). Data were analyzed by means of descriptive statistics such as frequencies, means and percentages. There were no significant differences in the responses of both newly-appointed and experienced deputy principals. The results revealed that deputy principals experienced administrative, financial management, work pressure, personal and physical resources problems. In an attempt to address the problems identified, a context-specific induction program is recommended. The induction program should be an on-going program of professional development and should preferably include specific aims, action steps to be taken to achieve the aims that are set and measures to evaluate progress

Low mortality of people living with diabetes mellitus diagnosed with COVID-19 and managed at a field hospital in Western Cape Province, South Africa

Background. The novel coronavirus disease 2019 (COVID-19) was declared an international pandemic by the World Health Organization in March 2020. Throughout the pandemic, the association between diabetes mellitus (DM) and more severe COVID-19 has been well described internationally, with limited data, however, on South Africa (SA). The role of field hospitals in the management of patients with COVID-19 in SA has not yet been described. Objectives. To describe the mortality and morbidity of people living with DM (PLWD) and comorbid COVID-19, as well as to shed light on the role of intermediate facilities in managing DM and COVID-19 during the pandemic. Methods. This is a single-centre cross-sectional descriptive study that included all patients with confirmed COVID-19 and pre-existing or newly diagnosed DM (of any type) admitted to the Cape Town International Convention Centre (CTICC) Intermediate Care Bed Facility from June 2020 to August 2020. This study presents the profile of patients admitted to the CTICC, and reports on the clinical outcome of PLWD diagnosed with COVID-19, and additionally determines some associations between risk factors and death or escalation of care in this setting. Results. There were 1 447 admissions at the CTICC, with a total of 674 (46.6%) patients who had confirmed DM, of whom 125 (19%) were newly diagnosed diabetics and 550 (81%) had pre-existing DM. Included in this group were 57 referrals from the telemedicine platform – a platform that identified high-risk diabetic patients with COVID-19 in the community, and linked them directly to hospital inpatient care. Of the 674 PLWD admitted, 593 were discharged alive, 45 were escalated to tertiary hospital requiring advanced care and 36 died. PLWD who died were older, had more comorbidities (specifically chronic obstructive pulmonary disease, congestive cardiac failure and chronic kidney disease) and were more likely to be on insulin.Conclusions. In a resource-limited environment, interdisciplinary and interfacility collaboration ensured that complicated patients with DM and COVID-19 were successfully managed in a field hospital setting. Telemedicine offered a unique opportunity to identify high-risk patients in the community and link them to in-hospital monitoring and care. Future studies should explore ways to optimise this collaboration, as well as to explore possibilities for early identification and management of high-risk patients

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

A community approach for pathogens and their arthropod vectors (ticks and fleas) in cats of sub-Saharan Africa

Background Arthropod-borne pathogens and their vectors are present throughout Africa. They have been well studied in livestock of sub-Saharan Africa, but poorly studied in companion animals. Given their socioeconomic importance, the African Small Companion Animal Network (AFSCAN), as part of the WSAVA Foundation, initiated a standardized multi-country surveillance study. Methods In six countries (Ghana, Kenya, Nigeria, Tanzania, Uganda, and Namibia) in both rural and urban settings, 160 infested cats were sampled to assess their ectoparasite community (ticks and fleas), as well as the micro-parasite prevalence within those ectoparasites (60 and 118 pools of ticks and fleas, respectively) and blood (276 cats, including 116 non-infested). Results Almost two thirds of all infested cats originated from Tanzania and Kenya. Despite the large macro-geographical variation, no consistent difference was found in ectoparasite diversity and numbers between East and West Africa. Far more flea-infested than tick-infested cats were found. The most dominant ectoparasite was Ctenocephalides felis. Among the ticks, the exophilic Haemaphysalis spp. were the commonest, including species that are not typically linked with companion animals (Haemaphysalis spinulosa and Haemaphysalis elliptica). The most prevalent pathogens found in the blood and fleas were Bartonella henselae and Mycoplasma haemofelis. In the ticks, the dog-associated Hepatozoon canis was most commonly found. A high degree of co-parasitism was found in all countries and habitats. Conclusions Our continent-wide standardized field study highlights the cat’s potential to serve as a reservoir of pathogens that can be transmitted to humans or livestock, especially when cats are expected to become more commonly kept in African villages and towns

A urinary biosignature for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS)

We used a comprehensive metabolomics approach to study the altered urinary metabolome of two mitochondrial myopathy, encephalopathy lactic acidosis and stroke like episodes (MELAS) cohorts carrying the m.3243A > G mutation. The first cohort were used in an exploratory phase, identifying 36 metabolites that were significantly perturbed by the disease. During the second phase, the 36 selected metabolites were able to separate a validation cohort of MELAS patients completely from their respective control group, suggesting usefulness of these 36 markers as a diagnostic set. Many of the 36 perturbed metabolites could be linked to an altered redox state, fatty acid catabolism and one-carbon metabolism. However, our evidence indicates that, of all the metabolic perturbations caused by MELAS, stalled fatty acid oxidation prevailed as being particularly disturbed. The strength of our study was the utilization of five different analytical platforms to generate the robust metabolomics data reported here. We show that urine may be a useful source for disease-specific metabolomics data, linking, amongst others, altered one-carbon metabolism to MELAS. The results reported here are important in our understanding of MELAS and might lead to better treatment options for the disease.Peer reviewe

Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors

Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism (Mistry et al., 2016), but their molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, BQCA, in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human M1 mAChR. Interactions between the orthosteric agonists and the novel PAMs or BQCA suggested their allosteric effects were solely governed by modulation of agonist affinity. The greatest degree of positive co-operativity was observed with higher efficacy agonists, whereas minimal potentiation was observed when the modulators were tested against the lower efficacy agonist, xanomeline. Each PAM was investigated for its effects on the endogenous agonist, ACh, on three different signalling pathways, (ERK1/2 phosphorylation, IP1 accumulation and β-arrestin-2 recruitment), revealing that the allosteric potentiation generally tracked with the efficiency of stimulus-response coupling and that there was little pathway bias in the allosteric effects. Thus, despite the identification of novel allosteric scaffolds targeting the M1 mAChR, the molecular mechanism of action of these compounds is largely consistent with a model of allostery previously described for BQCA, suggesting that this may be a more generalized mechanism for M1 mAChR PAM effects than previously appreciated

Development of novel 4‐arylpyridin‐2‐one and 6‐arylpyrimidin‐4‐one positive allosteric modulators of the M1 muscarinic acetylcholine receptor

This study investigated the structure‐activity relationships of 4‐phenylpyridin‐2‐one and 6‐phenylpyrimidin‐4‐one muscarinic M1 acetylcholine receptor (M1 mAChRs) positive allosteric modulators (PAMs). The presented series focuses on modifications to the core and top motif of the reported leads, MIPS1650 (1) and MIPS1780 (2). Profiling of our novel analogues showed that these modifications result in more nuanced effects on the allosteric properties compared to our previous compounds with alterations to the biaryl pendant. Further pharmacological characterisation of the selected compounds in radioligand binding, IP1 accumulation and β‐arrestin 2 recruitment assays demonstrated that despite primarily acting as affinity modulators, the PAMs displayed different pharmacological properties across the two cellular assays. The novel PAM 7f is a potential lead candidate for further development of peripherally‐restricted M1 PAMs, due to its lower blood‐brain‐barrier (BBB) permeability and improved exposure in the periphery compared to lead 2