South African healthcare reforms towards universal healthcare - where to next?

The National Assembly approval of the National Health Insurance (NHI) Bill represents an important milestone, but there are many uncertainties concerning its implementation and timeline. The challenges faced by the South African healthcare system are huge, and we cannot afford to wait for NHI to address them all. It is critical that the process of strengthening the health system to advance universal healthcare (UHC) begins now, and there are several viable initiatives that can be implemented without delay. This article examines potential scenarios after the Bill is passed and ways in which UHC could be advanced. It begins with an overview of the trajectory of health system reform since 1994, then examines the scenarios that may emerge once the Bill is passed by Parliament and makes a case for finding ways in which UHC could be advanced within the country, regardless of any legal or financial barriers that may delay or limit NHI implementation.

Thematic analysis of the challenges and options for the Portfolio Committee on Health in reviewing the National Health Insurance Bill.

The Portfolio Committee on Health (PCH) obtained public input on the National Health Insurance Bill from a wide array of individuals and organisations between May and September 2021. The record of these submissions collated by the Parliamentary Monitoring Group provided the source material for this article. The concerns, suggestions and other issues raised by respondents were analysed to determine what challenges and options the PCH needs to take seriously as they prepare the Bill for Parliament. Prominent issues raised included concerns about the proposed governance structure, flaws in the funding model, the risk of corruption, the constitutional and human rights at risk, limited access to care for several groups, and the unresolved nature of the medical benefits to be provided under the Bill. Future legal contestation of the Bill on several of these issues has the potential to stop or delay its implementation for a long time. The PCH has some hard decisions to make: whether to address these concerns with quite radical revisions of the bill, to omit problematic elements, or to leave it unchanged, and accept the contestation this will bring.

The role of the Minister of Health in the National Health Insurance Bill: Challenges and options for the Portfolio Committee on Health.

The Portfolio Committee on Health (PCH) is responsible for obtaining public input on the National Health Insurance Bill, reviewing the Bill based on these inputs, and presenting the final Bill to the National Assembly. More than 130 individuals, organisations and institutions requested to make oral presentations, which commenced on 18 May 2021. Drawing on Parliamentary Monitoring Group meeting summaries and the presentations and submissions made by 82 respondents between 18 May and 10 September 2021, we examine governance concerns, especially in relation to the role and powers of the Minister of Health, and respondents' proposals for addressing them, and outline the challenges and options for the PCH in responding to the proposals.

Microtubule disruption reduces metastasis more effectively than primary tumor growth.

Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.

Genomes of Novel Myxococcota Reveal Severely Curtailed Machineries for Predation and Cellular Differentiation.

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, nonsoil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring (Zodletone Spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of 13 distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g., FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine learning approaches based on a set of 634 genes informative of social lifestyle predicted a nonsocial behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities but carried genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 million years ago (Mya) in response to the rise of soil as a distinct habitat on Earth. IMPORTANCE The phylum Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcota are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota have been encountered in a wide range of nonsoil, predominantly anaerobic habitats, and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA, that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of 13 pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcota has occurred in response to soil formation as a distinct habitat on Earth.

Lipid tethering of breast tumor cells reduces cell aggregation during mammosphere formation.

Mammosphere assays are widely used in vitro to identify prospective cancer-initiating stem cells that can propagate clonally to form spheres in free-floating conditions. However, the traditional mammosphere assay inevitably introduces cell aggregation that interferes with the measurement of true mammosphere forming efficiency. We developed a method to reduce tumor cell aggregation and increase the probability that the observed mammospheres formed are clonal in origin. Tethering individual tumor cells to lipid anchors prevents cell drift while maintaining free-floating characteristics. This enables real-time monitoring of single tumor cells as they divide to form mammospheres. Monitoring tethered breast cancer cells provided detailed size information that correlates directly to previously published single cell tracking data. We observed that 71% of the Day 7 spheres in lipid-coated wells were between 50 and 150 µm compared to only 37% in traditional low attachment plates. When an equal mixture of MCF7-GFP and MCF7-mCherry cells were seeded, 65% of the mammospheres in lipid-coated wells demonstrated single color expression whereas only 32% were single-colored in low attachment wells. These results indicate that using lipid tethering for mammosphere growth assays can reduce the confounding factor of cell aggregation and increase the formation of clonal mammospheres.

Caesarean section rates in South Africa: A case study of the health systems challenges for the proposed National Health Insurance.

Broader policy research and debate on the issues related to the planning of National Health Insurance (NHI) in South Africa (SA) need to be complemented by case studies to examine and understand the issues that will have to be dealt with at micro and macro levels. The objective of this article is to use caesarean section (CS) as a case study to examine the health systems challenges that NHI would need to address in order to ensure sustainability. The specific objectives are to: (i) provide an overview of the key clinical considerations related to CS; (ii) assess the CS rates in the SA public and private sectors; and (iii) use a health systems framework to examine the drivers of the differences between the public and private sectors and to identify the challenges that the proposed NHI would need to address on the road to implementation.

Partial thermal imidization of polyelectrolyte multilayer cell tethering surfaces (TetherChip) enables efficient cell capture and microtentacle fixation for circulating tumor cell analysis.

The technical challenges of imaging non-adherent tumor cells pose a critical barrier to understanding tumor cell responses to the non-adherent microenvironments of metastasis, like the bloodstream or lymphatics. In this study, we optimized a microfluidic device (TetherChip) engineered to prevent cell adhesion with an optically-clear, thermal-crosslinked polyelectrolyte multilayer nanosurface and a terminal lipid layer that simultaneously tethers the cell membrane for improved spatial immobilization. Thermal imidization of the TetherChip nanosurface on commercially-available microfluidic slides allows up to 98% of tumor cell capture by the lipid tethers. Importantly, time-lapse microscopy demonstrates that unique microtentacles on non-adherent tumor cells are rapidly destroyed during chemical fixation, but tethering microtentacles to the TetherChip surface efficiently preserves microtentacle structure post-fixation and post-blood isolation. TetherChips remain stable for more than 6 months, enabling shipment to distant sites. The broad retention capability of TetherChips allows comparison of multiple tumor cell types, revealing for the first time that carcinomas beyond breast cancer form microtentacles in suspension. Direct integration of TetherChips into the Vortex VTX-1 CTC isolation instrument shows that live CTCs from blood samples are efficiently captured on TetherChips for rapid fixation and same-day immunofluorescence analysis. Highly efficient and unbiased label-free capture of CTCs on a surface that allows rapid chemical fixation also establishes a streamlined clinical workflow to stabilize patient tumor cell samples and minimize analytical variables. While current studies focus primarily on CTC enumeration, this microfluidic device provides a novel platform for functional phenotype testing in CTCs with the ultimate goal of identifying anti-metastatic, patient-specific therapies.

The Competition Commission Health Market Inquiry Report: An overview and key imperatives.

The Competition Commission's Health Market Inquiry (HMI) is the most systematic and comprehensive investigation carried out into the South African private health sector. The recommendations as set out in the HMI Final Report merit extensive discussion and debate, as they could - if implemented - have far-reaching consequences for the future of the healthcare system. The objective of this article is to contribute to this discussion by providing an overview of the key findings and recommendations of the HMI and highlighting the resultant key imperatives at this critical juncture of policy development.

Single-Cell Tracking of Breast Cancer Cells Enables Prediction of Sphere Formation from Early Cell Divisions.

The mammosphere assay has become widely employed to quantify stem-like cells in a population. However, the problem is there is no standard protocol employed by the field. Cell seeding densities of 1,000 to 100,000 cells/mL have been reported. These high densities lead to cellular aggregation. To address this, we have individually tracked 1,127 single MCF-7 and 696 single T47D human breast tumor cells by eye over the course of 14 days. This tracking has given us detailed information for the commonly used endpoints of 5, 7, and 14 days that is unclouded by cellular aggregation. This includes mean sphere sizes, sphere-forming efficiencies, and a well-defined minimum size for both lines. Importantly, we have correlated early cell division with eventual sphere formation. At 24 hr post seeding, we can predict the total spheres on day 14 with 98% accuracy in both lines. This approach removes cell aggregation and potentially shortens a 5- to 14-day assay to a 24 hours.

Real-time scratch assay reveals mechanisms of early calcium signaling in breast cancer cells in response to wounding.

Aggressive cellular phenotypes such as uncontrolled proliferation and increased migration capacity engender cellular transformation, malignancy and metastasis. While genetic mutations are undisputed drivers of cancer initiation and progression, it is increasingly accepted that external factors are also playing a major role. Two recently studied modulators of breast cancer are changes in the cellular mechanical microenvironment and alterations in calcium homeostasis. While many studies investigate these factors separately in breast cancer cells, very few do so in combination. This current work sets a foundation to explore mechano-calcium relationships driving malignant progression in breast cancer. Utilizing real-time imaging of an in vitro scratch assay, we were able to resolve mechanically-sensitive calcium signaling in human breast cancer cells. We observed rapid initiation of intracellular calcium elevations within seconds in cells at the immediate wound edge, followed by a time-dependent increase in calcium in cells at distances up to 500µm from the scratch wound. Calcium signaling to neighboring cells away from the wound edge returned to baseline within seconds. Calcium elevations at the wound edge however, persisted for up to 50 minutes. Rigorous quantification showed that extracellular calcium was necessary for persistent calcium elevation at the wound edge, but intercellular signal propagation was dependent on internal calcium stores. In addition, intercellular signaling required extracellular ATP and activation of P2Y2 receptors. Through comparison of scratch-induced signaling from multiple cell lines, we report drastic reductions in response from aggressively tumorigenic and metastatic cells. The real-time scratch assay established here provides quantitative data on the molecular mechanisms that support rapid scratch-induced calcium signaling in breast cancer cells. These mechanisms now provide a clear framework for investigating which short-term calcium signals promote long-term changes in cancer cell biology.

The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus.

A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (n = 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m(2), HbA(1c) = 7.7 ± 0.3%) and normal glucose-tolerant (NGT) subjects (n = 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m(2), HbA(1c) = 5.6 ± 0.1%) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function [disposition index (DI)] was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine [TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin] values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8; p < 0.001). IS positively correlated with fasting plasma glucose (r = 0.638, p < 0.001), 1-h plasma glucose (r = 0.483, p = 0.005), 2-h plasma glucose (r = 0.611, p < 0.001) and HbA1c (r = 0.469, p = 0.007). IS was inversely correlated with insulin sensitivity (r = -0.478, p = 0.006) and DI (r = -0.523, p = 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (M/I < 4). A state of subclinical inflammation defined and quantifiable by inflammatory score including TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin is associated with both hyperglycemia and whole-body insulin resistance in T2DM.

Fractional anisotropy of water diffusion in cerebral white matter across the lifespan.

Determining the time of peak of cerebral maturation is vital for our understanding of when cerebral maturation ceases and the cerebral degeneration in healthy aging begins. We carefully mapped changes in fractional anisotropy (FA) of water diffusion for eleven major cerebral white matter tracts in a large group (831) of healthy human subjects aged 11-90. FA is a neuroimaging index of micro-structural white matter integrity, sensitive to age-related changes in cerebral myelin levels, measured using diffusion tensor imaging. The average FA values of cerebral white matter (WM) reached peak at the age 32 ± 6 years. FA measurements for all but one major cortical white matter tract (cortico-spinal) reached peaks between 23 and 39 years of age. The maturation rates, prior to age-of-peak were significantly correlated (r=0.74; p=0.01) with the rates of decline, past age-of-peak. Regional analysis of corpus callosum (CC) showed that thinly-myelinated, densely packed fibers in the genu, that connect pre-frontal areas, maturated later and showed higher decline in aging than the more thickly myelinated motor and sensory areas in the body and splenium of CC. Our findings can be summarized as: associative, cerebral WM tracts that reach their peak FA values later in life also show progressively higher age-related decline than earlier maturing motor and sensory tracts. These findings carry multiple and diverse implications for both theoretical studies of the neurobiology of maturation and aging and for the clinical studies of neuropsychiatric disorders.

Latest developments at GANIL for stable and radioactive ion beam production.

In the frame of the SPIRAL II (Système de Production d'Ions Radioactifs Accélérés en Ligne Partie II) project, several developments of stable and radioactive ion production systems have been started up. In parallel, GANIL has the ambition to preserve the existing stable and radioactive beams and also to increase its range by offering new ones. In order to identify the best directions for this development, a new group called GANISOL has been formed. Its preliminary conclusions and the latest developments at GANIL are presented.

Status report of stable and radioactive ion beam production at GANIL.

GANIL has been producing many stable and radioactive ion beams for nearly 25 years. Constant progresses have been made in terms of intensity, stability, and reliability. The intensity for some stable metallic beams now exceeds or approaches the p microA level at an energy up to 95 MeV/u, e.g., 1.14 p microA for (36)S (65% enriched) at 77 MeV/u, 0.35 p microA for (58)Ni (63% enriched) at 74 MeV/u. Some recent results with Magnesocene using the metallic ions from volatile compounds method should also make possible the production of metallic beams with an intensity greater than 1 p microA. This has still to be measured. The ISOL facility SPIRAL I has been in operation for almost six years. Up to now, 17 exotic He experiments have been done with 14 target/ion-source (TIS) units; 19 other experiments (with O, Ne, Ar, and Kr) have been achieved with 14 TISs. Statistics show a fairly good ratio of available beam time to scheduled beam time. The radioactive beams and available intensities are compiled in this report. Future developments on radioactive ion beam production are briefly presented, while more details will be discussed elsewhere at this conference.

Development of a 1+/N+ setup for the production of multicharged radioactive alkali ions in SPIRAL.

In the framework of the production of radioactive ion beams by the isotope separator online method, a new system has been developed at GANIL/SPIRAL I to produce multicharged alkali ions. The principle, referred to as the "direct 1+/N+ method," consists of a surface ionization source associated with a multicharged electron-cyclotron-resonance ion source without an intermediate mass separator. This new system has been tested online using a (48)Ca primary beam at 60.3 A MeV. The experimental evidence of the direct 1+/N+ process has been obtained for a potential difference between the two sources of 11 V and with a 1+/N+ charge breeding efficiency of 0.04% for (47)K(5+). This value is significantly lower than the value of 6% obtained for stable K ions with the standard 1+/N+ method. A possible explanation is given in the text.

Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia.

Recent studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for some types of infections. The present study aimed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged >65 yrs and hospitalised with community-acquired pneumonia. A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged >/=65 yrs hospitalised with community-acquired pneumonia, and having >/=1 yr of prior Veterans Affairs outpatient care. In total, 8,652 subjects were identified with a mean age of 75 yrs, 98.6% were male, and 9.9% of subjects died within 30 days of presentation. In this cohort, 18.1% of subjects were using statins and 33.9% were using ACE inhibitors. After adjusting for potential confounders, current statin use (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.42-0.70) and ACE inhibitor use (OR 0.80, 95% CI 0.68-0.89) were significantly associated with decreased 30-day mortality. Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia. Randomised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial.

Exposure and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in tree swallows (Tachycineta bicolor) nesting along the Woonasquatucket River, Rhode Island, USA.

Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in tree swallows (Tachycineta bicolor) nesting along the Woonasquatucket River northwest of Providence (RI, USA) in 2000 and 2001 were some of the highest ever reported in avian tissues. Mean concentrations in eggs ranged from 300 to >1,000 pg/g wet weight at the two most contaminated ponds, Allendale and Lyman. Mean egg concentrations at Greystone, the upstream reference pond, were 12 and 29 pg/g. Positive accumulation rates and concentrations in diet samples from 12-day-old nestlings indicated that the contamination was accumulated locally. Concentrations in diet of between 71 and 219 pg/g wet weight were more than 6 and 18 times higher than concentrations considered safe for birds (10-12 pg/g). Hatching success was negatively associated with concentration of TCDD in eggs. Only about half the eggs hatched at Allendale compared with >77% at Greystone. The national average for hatching success in successful nests is 85%. No other contaminants, such as polychlorinated biphenyls and mercury, were present in any sample at concentrations known to affect avian reproduction. Three bioindicators, half-peak coefficient of geometric variation, ethoxyresorufin-O-dealkylase activity, and brain asymmetry were assessed relative to TCDD contamination.

Antibiotics for acute maxillary sinusitis.

BACKGROUND: For adults seeking care in ambulatory medical practices, sinusitis is the most common diagnosis treated with antibiotics. OBJECTIVES: We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in December 2001, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes, for acute maxillary sinusitis. Additional criteria for inclusion were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement, and a sample size of 30 or more adults. Of 2058 potentially relevant studies, two or more reviewers identified 49 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were: a) clinical cure, and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Forty-nine trials, involving 13,660 participants, evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic versus control (n of 5); newer, non-penicillin antibiotic versus penicillin class (n of 10); and amoxicillin-clavulanate versus other extended spectrum antibiotics (n of 17), where n is the number of trials. Most trials were conducted in otolaryngology settings. Only 8 trials described adequate allocation and concealment procedures; 20 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72; 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53) but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins versus penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins versus amoxicillin-clavulanate (RR for cure 1.03; 95% CI 0.96 to 1.11). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics (RR 0.47; 95% CI 0.30 to 0.73). Relapse rates within one month of successful therapy were 7.7%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports the use of penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.