Binuclear palladacycles with ionisable and non-ionisable tethers as anticancer agents.

The search for novel anticancer agents to replace the current platinum-based treatments remains an ongoing process. Palladacycles have shown excellent promise as demonstrated by our previous work which yielded BTC2, a binuclear palladadycle with a non-ionisable polyethylene glycol (PEG) tether. Here, we explore the importance of the PEG-tether length on the anticancer activity of the binuclear palladacycles by comparing three analogous binuclear palladacycles, BTC2, BTC5 and BTC6, in the oestrogen receptor positive MCF7 and triple-negative MDA-MB-231 breast cancer cell lines. In addition, these are compared to another analogue with an ionisable morpholine tether, BTC7. Potent anticancer activity was revealed through cell viability studies (MTT assays) revealed that while BTC6 showed similar potent anticancer activity as BTC2, it was less toxic towards non-cancerous cell lines. Interestingly, BTC7 and BTCF were less potent than the PEGylated palladacycles but showed significantly improved selectivity towards the triple-negative breast cancer cells. Cell death analysis showed that BTC7 and BTCF significantly induced apoptosis in both the cancer cell lines while the PEGylated complexes induced both apoptosis and secondary necrosis. Furthermore, experimental and computational DNA binding studies indicated partial intercalation and groove binding as the modes of action for the PEGylated palladacycles. Similarly, experimental and computational BSA binding studies indicated and specific binding sites in BSA dependent on the nature of the tethers on the complexes.

A qualitative exploration of forensic pathology service staff perceptions of the implementation barriers and facilitators of manual- and electronic injury mortality surveillance system methods in South Africa.

BACKGROUND: Injury mortality surveillance systems are critical to monitor changes in a population's injury outcomes so that relevant injury prevention responses may be adopted. This is particularly the case in South Africa, where the injury burden is nearly twice the global rate. Regular evaluations of surveillance systems are pivotal to strengthening surveillance capacity, performance, and cost effectiveness. The National Injury Mortality Surveillance System (NIMSS) is an injury mortality surveillance system that is currently focused in Mpumalanga and utilises manual and electronic web-based systems for data collection. This study explored Forensic Pathology Service (FPS) staff perceptions of the implementation barriers and facilitators of manual- and electronic injury mortality surveillance system methods. METHODS: A qualitative study was employed using purposive sampling. Forty-seven participants, aged 29 to 59 years comprising 31 males and 16 females were recruited across 21 FPS facilities that serve the province. The formative evaluation occurred over the November 2019 to November 2022 period. Twelve focus group discussions were thematically analysed to determine emerging themes and patterns related to the use of the system using the WHO surveillance system guidelines as a framework. RESULTS: The key themes concerning the barriers and facilitators were located along WHO attributes of simplicity, acceptability, timeliness, flexibility, data quality and stability. Distinctions between the manual and e-surveillance systems were drawn upon across the attributes highlighting their experience with the system, user preference, and its contextual relevance. With Mpumalanga predominantly rural, internet connectivity was a common issue, with most participants consequently showing a preference for the manual system, even though the electronic system's automated internal validation process was of benefit. The data quality however remained similar for both methods. With program stability and flexibility, the manual system proved more beneficial as the dataset was reported to be easily transferrable across computer devices. CONCLUSION: Obtaining FPS perceptions of their experiences with the system methodologies are pertinent for the enhancement of injury surveillance systems so to improve prospective engagements with the systems. This will facilitate timely and accurate injury mortality information which is vital to inform public policy, and injury control and prevention responses.

Driver intoxication and risk for fatal crashes in South Africa: A 3-year review.

BACKGROUND:  Globally, alcohol intoxication has been shown to be significantly associated with increased risk for road traffic crash morbidity and mortality for all road users (drivers, passengers and pedestrians). This association relates to the diminished capacity of drivers while intoxicated to operate motor vehicles and the increased propensity for risk-taking behaviours. The overall prevalence of alcohol-related fatal crashes contributes significantly to the burden of disease in many countries. In South Africa, research into the relationship between alcohol intoxication and other driver risk behaviours is limited and variable, constraining appropriate and effective policy and programmatic options and interventions. OBJECTIVES:  To examine the risk for fatal crashes attributed to driver alcohol intoxication relative to speeding and other driver risk behaviours across a range of key crash and vehicle characteristics and temporal variables. METHODS:  The study used a sample of fatal crashes drawn from the Road Traffic Management Corporation database for the period 2016 - 2018, comprising 13 074 fatal crashes. An overview of the sample data is provided using descriptive statistics. Following this, logistic regression modelling was undertaken to examine and clarify the risk for alcohol-attributed fatal crashes against that for speeding and a combined category of all other driver risks using variables relating to crash complexity, vehicle characteristics and regulation, and temporal variables for day/night, weekday/weekend and vacation/non-vacation periods. RESULTS:  Compared with fatal crashes involving only the driver, the study revealed a significantly greater risk for alcohol-attributed fatal crashes in instances involving more complexity as measured by involvement of other road users (pedestrians and other drivers). Additionally, the risk for alcohol-attributed fatal crashes was significantly greater for light vehicles and buses/midibuses compared with trucks. Road users were also at greater risk for such crashes at night, over long and regular weekends, and during non-vacation periods of the year. CONCLUSIONS:  Improved enforcement to prevent alcohol intoxication using roadblocks is required in a focused manner during specific temporal periods (at night, over weekends and during non-vacation periods), while enforcement to prevent speeding and other driver risks should be prioritised during other periods using speed monitoring and mobile visible policing, respectively. There is an urgent need to improve the current measurement of alcohol attribution in fatal crashes, to ensure more accurate estimation of prevalence, and to improve analysis and understanding of the compound impact of alcohol intoxication on all other driver risk behaviours and associated fatal crashes.

Common variable immunodeficiency disorders: What generalists should know.

Primary immune deficiency disorders (PIDDs) are common and underdiagnosed. Predominant antibody deficiencies (PADs) are the most common type of immune deficiency and comprise 55% of the immune deficiencies diagnosed.[1] Although immunoglobulin A (IgA) deficiency remains the most common type of PID, common variable immunodeficiency disorders remain the most common symptomatic PID for which medical therapy is sought.

The use of disinfection tunnels or disinfectant spraying of humans as a measure to reduce the spread of the SARS-CoV-2 virus.

In endeavouring to mitigate the spread of the SARS-CoV-2 virus, a concerning practice of spraying individuals with disinfectant via so-called 'disinfection tunnels' has come to light. The Allergy Society of South Africa supports the World Health Organization in strongly condemning all human spraying, owing to lack of efficacy and potential dangers, especially to patients with coexisting allergic conditions.

Chronic rhinitis in South Africa - more than just allergy!

Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.

Child health, infant formula funding and South African health professionals: Eliminating conflict of interest.

Letters by Van Niekerk and Khan on article by Lake et al. (Lake L, Kroon M, Sanders D, et al. Child health, infant formula funding and South African health professionals: Eliminating conflict of interest. S Afr Med J 2019;109(12):902-906. https://doi.org/10.7196/SAMJ.2019.v109i12.14336); and response by Lake et al.

Paraffin dangers, health and socioeconomic consequences: Urgent need for policy action.

Illuminating paraffin (kerosene) is the primary cooking fuel for approximately two million South Africans. The highly flammable and toxic fuel is burnt in poorly made stoves that are prone to malfunction and are associated with accidental fires, burns and household air pollution. However, the fuel continues to be used as it is easily decanted, widely available in neighbourhood outlets, perceived as affordable, and often the only available option for low-income urban settlements. It is anticipated that increased and enforced home congestion during COVID-19 lockdowns will exacerbate exposure of homebound families to unsafe energy, especially during the cold winter months. Based on an accumulation of evidence on the health and socioeconomic impacts of paraffin, this article advocates for its expedited phase-out and substitution with safer energy.

Data set for influence of blends of diesel and renewable fuels on compression ignition engine emissions.

The present data article is based on the research work which investigates the influence of blends of diesel and renewable fuels on compression ignition engine emissions. In this experimental work, a 2.4 L, turbocharged, direct injection compression ignition engine and water brake dynamometer were used. Different ternary blends were created by mixing diesel, biodiesel and ethanol together in accordance with a mixture design of experiments. The homogeneity of each ternary blend was qualitatively checked by observing the samples for 24 hours for visible separation. The engine was run over the WLTP drive cycle for each individual ternary blend and the exhaust emissions were recorded. NOVA 7466K and TESTO 350 gas analysers were used to record the exhaust emissions. A factory standard MAF sensor was used to record the inlet air mass flow and an aftermarket ECU was used to determine the fuel flow. The ternary blends were blended using standard laboratory measuring equipment.

Is 'decolonisation' a legitimate and appropriate value in biomedical research and teaching?

This article investigates the claim that decolonisation is an appropriate and legitimate value in the process of current-day biomedical research, particularly in Africa. Can we expect that the nature and effects of the decolonisation of research will be comparable and similar for all scientific disciplines (obviously including the biomedical disciplines), or does the claim to significant differences between the 'natural'and 'human' sciences have notable implications for our understanding of both the nature and the effects of decolonisation, as well as for our understanding of the biomedical disciplines themselves? In this article I firstly analyse the notion of decolonisation . Secondly, I investigate the legitimacy of holding and maintaining a conceptual difference between the natural and the human sciences. I do this in conversation with Charles Taylor and Jürgen Habermas, who have produced invaluable contributions in this regard. Thirdly, I apply these insights to the question as to whethethedecolonialist project (the general legitimacy of which I accept) is equally applicable to both the natural and the human sciencesin their traditional formats. Finally, I discuss the relevance of this debate for both the nature of the biomedical sciences and the question as to the extent to which the biomedical sciences can and ought to be successfully decolonised ­ a question that is answered in the affirmative

Child understandings of the causation of childhood burn injuries: Child activity, parental domestic demands, and impoverished settings.

BACKGROUND: Burns are a global public health problem. In South Africa, the rate of paediatric burn deaths is 5 times higher than other upper middle-income countries, with concentrations in impoverished settings. Globally, the majority of research focuses on expert and caregiver descriptions of burn occurrence, causation, and prevention, with limited consideration of children's perspectives. This study investigated children's understanding of the causation and prevention of childhood burns. METHODS: Data were collected from eighteen 10- to 11-year-old children living in selected impoverished, fire-affected neighbourhoods in Cape Town, through 3 isiXhosa focus groups. All focus groups were transcribed, coded, and analysed for emerging themes through thematic analysis. RESULTS: Themes regarding burn causation and risks centred around 4 themes: (a) developmental limits in context; (b) domestic chores, child capacity, and inability to say "no"; (c) inadequate supervision and compromised caregiving; and (d) unsafe structures. Child accounts of prevention pertained to (e) burn injury prevention activities in comprised environments and emphasized child agency, and upgrading the physical environment. CONCLUSION: The children in this study ascribed burn injuries as the consequence of their developmental limits in the context of poverty, constraints on parental supervision, and unsafe environments. The children recommended safety education and upgrading their physical environments as part of burns injury prevention. The child accounts offer useful insights to inform safety interventions in impoverished settings.

Household and caregiver characteristics and behaviours as predictors of unsafe exposure of children to paraffin appliances.

This study examines adult safety knowledge and practices regarding the use of paraffin cooking appliances. The use of these is common in South Africa with injury risks that are poorly understood. This cross-sectional study was in an informal settlement in Johannesburg, South Africa, where children were reportedly at high risk for burns. This study sought to clarify relationships between key risks and developed individual and composite variables from theoretical constructs and operational definitions of risks for burns. Risks included Child Use of Paraffin Appliances, Child Proximity to Cooking, Risky Stove Use, Caregiver's Burn Treatment Knowledge, Children Locked in House, Children Alone in House. Number of children remains as in proof as this was not a composite scale. Child Proximity to Cooking was associated with more children in the home. Households where children were in greater proximity to cooking were 6 times more likely to be left alone at home, with caregivers with no education over 100 times more likely to lock their children at home. Children locked in were often from homes where caregivers used appliances unsafely. In settings with hazardous energy use, compressed household configurations, and families with multiple children, Risky Stove Use and the practice of locking children in the home may be catastrophic.

Feasibility of Pulse Oximetry Pre-discharge Screening Implementation for detecting Critical Congenital heart Lesions in newborns in a secondary level maternity hospital in the Western Cape, South Africa: The 'POPSICLe' study.

BACKGROUND: Early detection of critical congenital heart disease (CCHD) through newborn pulse oximetry (POx) screening is an effective strategy for reducing paediatric morbidity and mortality rates and has been adopted by much of the developed world. OBJECTIVES: To document the feasibility of implementing pre-discharge POx screening in well babies born at Mowbray Maternity Hospital, a busy government hospital in Cape Town, South Africa. Parent and staff acceptance was assessed. METHODS: We conducted a prospective study of predischarge POx screening in one postnatal ward, following informed parental consent. RESULTS: During the 4-month study period, 1 017 of 2 256 babies discharged (45.1%) were offered POx screening and 1 001 were screened; 94.0% of tests took <3 minutes to perform, 4.3% 3 - 5 minutes and 1.7% >5 minutes. Eighteen patients needed second screens and three required third screens. Only 3.1% protocol errors were made, all without consequence. The vast majority (91.6%) of nursing staff reported insufficient time to perform the study screening in addition to their daily tasks, but ~75% felt that with a full nursing staff complement and if done routinely (not part of a study), pre-discharge POx screening could be successfully instituted at our facility. Over 98% of the mothers had positive comments. Two babies failed screening and required echocardiograms; one was diagnosed with CCHD and the other with neonatal sepsis. The sensitivity and specificity were 50% (95% confidence interval (CI) 1.3 - 98.7%) and 99.9% (95% CI 99.4 - 100%), respectively, with a percentage correct of 99.8%. CONCLUSIONS: POx screening was supported and accepted by staff and parents. If there are no nursing staff shortages and if it is done routinely before discharge, not as part of a study, we conclude that POx screening could be implemented successfully without excessive false positives or errors, or any additional burden to cardiology services.

Prevalence of Blomia tropicalis allergy in two regions of South Africa.

BACKGROUND: Asthma and allergic rhinitis affect 15% and 38% of South African (SA) children, respectively. The housedust mite (HDM) is the most significant indoor aeroallergen. Typical HDM species include Dermatophagoides pteronyssinus, D. farinae and Blomia tropicalis. Conventional skin-prick testing (SPT) panels only test for Dermatophagoides. B. tropicalis has been described in the tropical and subtropical regions, but is not routinely tested for in SA. OBJECTIVE: To ascertain the significance of B. tropicalis as an aeroallergen in northern coastal KwaZulu-Natal Province (KZN), a tropical environment, and in Johannesburg in the highveld, where the climate is milder and less humid. METHODS: Children aged 1-18 years with features of allergic rhinitis and/or asthma were recruited over a 6-month period from Alberlito Hospital in northern KZN and the Clinton Clinic in Johannesburg. SPTs included Dermatophagoides and B. tropicalis. Sensitisation was defined as a wheal 3 mm greater than the negative control. RESULTS: Eighty-five subjects were included, 50 in northern KZN and 35 in the Johannesburg arm; 52% of subjects in northern KZN and 3% in Johannesburg were sensitised to B. tropicalis, with a significant difference between these centres (p<0.05). Of the 52% sensitised to B. tropicalis in northern KZN, half were sensitised only to B. tropicalis. CONCLUSION: There is a high prevalence of B. tropicalis allergy in the tropical northern KZN region and a much lower prevalence in the Johannesburg region. Routine testing for B. tropicalis allergy should be employed in northern KZN.

Childhood psychosocial development and fatal injuries in Gauteng, South Africa.

BACKGROUND: In South Africa, injuries are the third leading cause of death and disability. Children are especially susceptible to unintentional injuries, especially pedestrian injuries, burns and drowning. Injury risk is informed by children's exposure to adverse environmental circumstances, and individual capacities dependent on developmental maturity. Boys are at greater risk than girls. This study investigates the incidence of fatal childhood injuries as well as sex differences across psychosocial development stages. METHODS: Data on fatal injuries in Gauteng, South Africa's most populous province, were obtained from the National Injury Mortality Surveillance System. The analysis drew on Erikson's psychosocial theory of development which was used to create meaningful age groups. Age-specific population data from the 2011 Census were used to calculate rates, and significant differences were determined through the generation of risk ratios and confidence intervals. RESULTS: There were 5404 fatal injuries among children in Gauteng from 2008 to 2011. The average age of victims was 8.9 years, and the majority male (65.6%). In infancy, the mortality rates for all injuries and non-traffic unintentional injuries were significantly higher than for the other age groups. Burns were the most common cause of death in infancy and early childhood. Pedestrian injuries accounted for a third of mortality in preschool and school age, and homicide rates were significantly higher in adolescence than in the other developmental stages. For injuries in general, boys had significantly higher mortality rates than girls in all age groups except preschool. The only instance where the mortality rate for girls was significantly higher than for boys was for adolescent ingestion poisoning suicides. CONCLUSIONS: The exposure to environmental and social risks is differentially moderated with maturing age and levels of autonomy. The sex of the child also informs risk. The nature of these risks is important when considering child injury prevention strategies.

Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa.

BACKGROUND: A high rate of congenital cytomegalovirus (CMV) has been documented in human immunodeficiency virus (HIV)-exposed infants in industrialized settings, both in the pre- and post-highly active antiretroviral therapy (HAART) era. Only limited data on the birth prevalence of congenital CMV among infants of HIV-infected women on prenatal antiretroviral (ARV) prophylaxis are available from sub-Saharan Africa, despite a high prevalence of both infections. We evaluated the prevalence of congenital CMV in HIV-exposed infants in the Western Cape, South Africa. METHODS: HIV-infected mothers were recruited in the immediate postnatal period at a referral maternity hospital between April and October 2012. Maternal and infant clinical data and newborn saliva swabs were collected. Saliva swabs were assayed by real-time polymerase chain reaction for CMV. Data were analyzed using univariate and multivariate logistic regression analyses to determine specific demographic, maternal, and newborn characteristics associated with congenital CMV. RESULTS: CMV was detected in 22 of 748 newborn saliva swabs (2.9%; 95% confidence interval [CI], 1.9%-4.4%). Overall, 96% of mothers used prenatal ARV prophylaxis (prenatal zidovudine, 43.9%; HAART, 52.1%). Maternal age, gestational age, prematurity (<37 weeks' gestation), type of ARV prophylaxis, length of ARV prophylaxis, birth weight, small for gestational age, and infant feeding choice were not significantly different between CMV-infected and -uninfected infants. Maternal CD4 count <200 cells/µL during pregnancy was independently associated with congenital CMV (adjusted odds ratio, 2.9; 95% CI, 1.2-7.3). A negative correlation between CMV load in saliva and maternal CD4 count was observed (r = -0.495, n = 22, P = .019). CONCLUSIONS: The birth prevalence of congenital CMV was high despite prenatal ARV prophylaxis, and was associated with advanced maternal immunosuppression.

Developing the evidence-base for Safe Communities: a multi-level, partly randomised, controlled trial.

Safe Communities, representing a global activation of the public health logic, may be strengthened through theoretical, methodological and empirical support. In the spirit of this Special Issue that aims to analyse the achievements and challenges inherent to Safe Communities, we offer our contribution in the form of a methodology of a multi-country child safety, peace and health promotion study. The study, situated within an African-centred initiative called Ukuphepha - an isiZulu word meaning demonstrating African safety - is underpinned by four theoretical claims that frame injury and violence prevention as a multi-disciplinary issue to be addressed through a suite of interventions to family and extended social systems. The interventions, sensitive to the priorities of each participating country, have been informed by the literature on effective interventions and the authors' joint experiences of community development. The study is designed as a population-based, multi-level, multi-intervention partly randomised controlled trial, and there are potentially 24 participant communities representing South Africa, Mozambique, Egypt, Zambia, Uganda, Bangladesh, Malaysia and Australia - over three commencement phases. Whereas process evaluation will focus on community engagement, impact evaluation will consider risk and protective factors, and outcome evaluation will examine the overall effectiveness of the interventions. Notwithstanding the many challenges, the study will provide insights into the methodology and mechanisms of ecologically-oriented interventions that locate injury and violence prevention as an activity arising from safety, peace and health promotion.

Quantification of volume loss and haemodynamic changes of Gelofusine-induced anaphylaxis during cardiopulmonary bypass.

A patient undergoing anaesthesia for coronary artery bypass surgery developed what was subsequently confirmed to be an anaphylactic reaction to succinylated gelatin (Gelofusine). By virtue of being on cardiopulmonary bypass, rapid detection, quantification and treatment of volume loss (by vasodilatation and extravasation) was possible. The patient required 51 ml/kg of resuscitative fluids in the 15 minutes after onset of anaphylaxis, or 73% of her calculated preoperative blood volume. Alpha-adrenoceptor agonists and vasopressin were required to manage ongoing vasoplegia. This case emphasises the importance of volume resuscitation and vasopressors in the treatment of anaphylaxis.