Interleukin 1-Beta (IL-1) Production by Innate Cells Following TLR Stimulation Correlates With TB Recurrence in ART-Treated HIV-Infected Patients

BACKGROUND: Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. METHODS: Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points prior to TB recurrence were stimulated with ligands for Toll like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multi-color flow cytometry and intracellular cytokine staining was used to detect IL-1β, TNF-α, IL-12 and IP10 responses from monocytes and myeloid dendritic cells (mDCs). RESULTS: Elevated production of IL-1β from monocytes following TLR-2, TLR-4 and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs respectively). CONCLUSION: Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB

Predictors of shoulder degeneration in the KwaZulu-Natal population of South Africa

The critical shoulder angle and acromion index are conventional radiological tools employed as predictors of shoulder degeneration. As they represent the static components of glenohumeral stability, the scapulo-humeral geometry and underlying subacromial tissue appear as the resultant cause-effect factors. Consequently. the purpose of this study was to investigate the critical shoulder angle and acromion index as interrelated parameters within the South African population. The measurement of both biomechanical parameters was conducted on two-hundred and sixty (n = 260) true AP radiographs. This was a cross-sectional study that also incorporated the demographic representation of the population group which was analysed accordingly. The mean values recorded for both the critical shoulder angle (36.31 +/- 5.84 degrees) and acromion index (0.74 +/- 0.13) suggested rotator cuff arthropathy. The results confirmed the theories of Nyffeler et al. (2006) and Moor et al. (2012) who alluded to glenoid inclination and the acromial coverage over the humeral head. A significant proportionality correlation, verified by a P value of 0.000, was established between the acromion index and critical shoulder angle which may assist to differentiate between normal asymptomatic shoulders and those with cuff disease. Furthermore, these predictors of shoulder degeneration may present as a preventative tool against tear progression

Improvements in the South African HIV care cascade: findings on 90-90-90 targets from successive population-representative surveys in North West Province.

IntroductionTo achieve epidemic control of HIV by 2030, countries aim to meet 90-90-90 targets to increase knowledge of HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression by 2020. We assessed the progress towards these targets from 2014 to 2016 in South Africa as expanded treatment policies were introduced using population-representative surveys.MethodsData were collected in January to March 2014 and August to November 2016 in Dr. Ruth Segomotsi Mompati District, North West Province. Each multi-stage cluster sample included 46 enumeration areas (EA), a target of 36 dwelling units (DU) per EA, and a single resident aged 18 to 49 per DU. Data collection included behavioural surveys, rapid HIV antibody testing and dried blood spot collection. We used weighted general linear regression to evaluate differences in the HIV care continuum over time.ResultsOverall, 1044 and 971 participants enrolled in 2014 and 2016 respectively with approximately 77% undergoing HIV testing. Despite increases in reported testing, known status among people living with HIV (PLHIV) remained similar at 68.7% (95% Confidence Interval (CI) = 60.9-75.6) in 2014 and 72.8% (95% CI = 63.6-80.4) in 2016. Men were consistently less likely than women to know their status. Among those with known status, PLHIV on ART increased significantly from 80.9% (95% CI = 71.9-87.4) to 91.5% (95% CI = 84.4-95.5). Viral suppression (<5000 copies/mL using DBS) among those on ART increased significantly from 55.0% (95% CI = 39.6-70.4) in 2014 to 81.4% (95% CI = 72.0-90.8) in 2016. Among all PLHIV an estimated 72.0% (95% CI = 63.8-80.1) of women and 45.8% (95% CI = 27.0-64.7) of men achieved viral suppression by 2016.ConclusionsOver a period during which fixed-dose combination was introduced, ART eligibility expanded, and efforts to streamline treatment were implemented, major improvements in the second and third 90-90-90 targets were achieved. Achieving the first 90 target will require targeted and improved testing models for men

Who really decides? Feeding decisions 'made' by caregivers of children with cerebral palsy.

BACKGROUND:  There are no definitive guidelines for clinical decisions for children with cerebral palsy (CP) requiring enteral feeds. Traditionally, medical doctors made enteral feeding decisions, while patients were essentially treated passively within a paternalistic 'doctor knows best' approach. Although a more collaborative approach to decision-making has been promoted globally as the favoured model among healthcare professionals, little is known about how these decisions are currently made practically. OBJECTIVES:  This study aimed to identify the significant individuals, factors and views involved in the enteral feeding decision-making process for caregivers of children with CP within the South African public healthcare sector. METHOD:  A single-case research design was used in this qualitative explorative study. Data were collected using semi-structured interviews and analysed using reflexive thematic analysis. RESULTS:  Four primary individuals were identified by the caregivers in the decision-making process: doctors, speech therapists, caregivers' families and God. Four factors were identified as extrinsically motivating: (1) physiological factors, (2) nutritional factors, (3) financial factors and (4) environmental factors. Two views were identified as intrinsically motivating: personal beliefs regarding enteral feeding tubes, and feelings of fear and isolation. CONCLUSION:  Enteral feeding decision-making within the South African public healthcare sector is currently still dominated by a paternalistic approach, endorsed by a lack of caregiver knowledge, distinct patient-healthcare provider power imbalances and prescriptive multidisciplinary healthcare dialogues.Contribution: This study has implications for clinical practice, curriculum development at higher education training facilities, and institutional policy changes and development, thereby contributing to the current knowledge and clinical gap(s) in the area.fals

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Background: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). Results: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes

Primary Care Staff's Views and Experiences Related to Routinely Advising Patients about Physical Activity. A Questionnaire Survey

Background: United Kingdom public health policy has recently re-emphasised the role of primary health care professionals in tackling increasing levels of physical inactivity within the general population. However, little is known about the impact that this has had in practice. This study explores Scottish primary care staff's knowledge, attitudes and experiences associated with advising patients about physical activity during routine consultations. Methods: A cross-sectional questionnaire survey of general practitioners (or family physicians), practice nurses and health visitors based in four health regions was conducted during 2004. The main outcome measures included: i) health professionals' knowledge of the current physical activity recommendations; (ii) practice related to routine physical activity advising; and (iii) associated attitudes. Results: Questionnaires were returned by 757 primary care staff (response rate 54%). Confidence and enthusiasm for giving advice was generally high, but knowledge of current physical activity recommendations was low. In general, respondents indicated that they routinely discuss and advise patients about physical activity regardless of the presenting condition. Health visitors and practice nurses were more likely than general practitioners to offer routine advice. Lack of time and resources were more likely to be reported as barriers to routine advising by general practitioners than other professional groups. However, health visitors and practice nurses were also more likely than general practitioners to believe that patients would follow their physical activity advice giving. Conclusion: If primary health care staff are to be fully motivated and effective in encouraging and supporting the general population to become more physically active, policymakers and health professionals need to engage in efforts to: (1) improve knowledge of current physical activity recommendations and population trends amongst frontline primary care staff; and (2) consider the development of tools to support individual assessment and advice giving to suit individual circumstances. Despite the fact that this study found that system barriers to routine advising were less of a problem than other previous research has indicated, this issue still remains a challenge

An evaluation of insulin therapy initiation among patients with type 2 diabetes attending a public health facility in South Africa

Background: Clinically effective interventions that could reduce diabetic patients’ risk of long-term complications are needed to contain the rising cost of diabetes care associated with the increasing prevalence of this condition. Good glycaemic control needs to be rapidly attained and maintained by the appropriate initiation and adjustment of glucoselowering therapy. In patients with insulin-requiring type 2 diabetes who are not at goal glycaemia, this translates to the initiation and intensification of insulin therapy. The aim of this study was to evaluate the appropriateness of the initiation of insulin therapy in patients with poorly controlled insulin-requiring type 2 diabetes.Method: This descriptive retrospective study evaluated treatment regimens, dose adjustments and glycated haemoglobin A1c (HbA1c) measurements extracted from records of patients with type 2 diabetes suitable for inclusion. The observation period spanned the 24 months retrospective to study start. Data collected were transcribed into a spreadsheet suitable for statistical analysis.Results: Of the overall cohort of patients with insulin-requiring type 2 diabetes (n = 131), only 45.8% (n = 60) were commenced on insulin during the observation period, of whom 51.7% had subsequent adjustment of insulin dosage. Mean HbA1c at insulin initiation was 10.29% (± 2.42), and 10.63% (± 1.93) after adjustment of insulin dose (p-value > 0.05). Of those who remained on oral glucose-lowering therapy (n = 71), 57.7% had no change in medication dosage throughout the study period. Overall, 81.35% remained ≥ 1% above goal HbA1c by the end of the study period.Conclusion: This study found a discrepancy in the appropriate use and adjustment of insulin therapy according to metabolic status

Bridging the transactional gap in Open Distance Learning (ODL): The case of the University of South Africa (Unisa)

The aim of this paper is to map and audit the availability and use of e-learning resources by Communication Science students at the University of South Africa (UNISA), in order to ensure that they provide a seamless learning experience to bridge the transactional distance in its Open Distance Learning (ODL) context. The Communication Science students targeted were COMSA executives and Unisa Radio employees. To serve the goal of the paper the following specific objectives were formulated: to establish types of e-learning resources available at Unisa, and to identify the benefits of elearning at Unisa. This study is informed by Michael Moore’s Transactional Distance theory. This theory, which focuses on dialogue, transactional distance and telecommunication systems, has been widely applied in many similar studies. A survey research design was used whereby questionnaires were administered to all COMSA executives and 50% of Unisa Radio student employees who were chosen using simple random sampling. The data gathered was analysed using thematic categorisation and tabulation and the findings were presented descriptively. The findings indicate that Unisa provides a variety of e-learning resources for its students. In addition, computers and the internet are most useful to students’ studies. It should be mentioned that e-learning facilitates and opens avenues for effective teaching. This study focused only on the availability and use of e-learning by Communication Science students at Unisa. Therefore, it will be necessary for a broader study to be undertaken which will focus on academic and ICT staff as well as students chosen across the Unisa community. Keywords: Open Distance Learning; E-learning; Online education; ICTs in teaching and learning, University of South Afric

INVESTIGATING CONSUMER RESPONSIVENESS TO MOBILE MARKETING IN JOHANNESBURG

Traditional communication mix elements have become pricey. Therefore there is a growing need for marketers to find cheaper alternatives to communicate with their target audience. Mobile phone marketing will lower the costs of advertising and at the same time improve relationships between marketers and consumers as it targets the personal element of marketing communication. According to research, 29 million people use mobile phones in South Africa. The research objectives seek to determine the different uses of mobile technology by consumers, how mobile phone users interact with mobile marketing techniques, and to make recommendations on the optimal use of mobile marketing. This quantitative study established that, although it might not be the first choice of receiving marketing communications, the majority of the people would still like to receive adverts via their mobile, proving that mobile marketing has a place in marketing. The findings revealed that 34% of South African mobile phone users have smartphones, this creates a new market for mobile internet, social media, and mobile email adverts. It is important that marketers should also use other methods of marketing communication mix as 28 million people use radio and 26 million people use televisions in South Africa, proving that these gadgets are still important in the consumers’ lives and in information sharing. Mobile marketing cannot replace the conventional marketing communication methods completely but can complement the efforts and create an interactive platform for marketers and their consumers