A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Parental perspectives towards sugar-sweetened beverages and polices: a qualitative study.

PURPOSE: This qualitative study aimed to understand parental perception of (1) sugar-sweetened beverages (SSB) and implications of SSB on health; (2) their role in shaping their children's consumption of SSB; (3) the influences on SSB consumption of their children; and (4) potential government policies targeted at controlling SSB consumption. METHODS: English-speaking parents of pre-schoolers aged 2-6 years were recruited. Semi-structured interviews based on the knowledge, attitude, practice framework were conducted, and transcripts were subjected to thematic analysis based on inductive approaches. Recruitment continued until data saturation was reached. RESULTS: Twenty parents participated in the study and themes addressing the objectives identified. (1) There were misconceptions regarding the healthfulness of certain non-packaged SSB such as traditional remedies and juices. Some were unaware about the association between SSB and dental caries. (2) The need to reduce and restrict sugar consumption for overall and oral health reasons was well-recognised, but the extent of control varied. (3) Multiple stakeholders including pre-schools, grandparents and domestic helpers were involved in shaping children's diet. Children's sugar intake was also influenced by environmental factors, such as the ubiquitously available SSB, targeted marketing and high cost of healthy alternatives. (4) Participants were less accepting towards SSB taxation than the ban of SSB sales. CONCLUSION: Despite the awareness of the types of SSBs and the general/oral health implications of sugar consumption, misconceptions exist. Although most parents possessed the knowledge and attitude, this did not translate into the practice of reducing sugar consumption in their children. There was no SSB reduction policy that had overwhelming acceptability.

Guidelines for the management of asthma in adults and adolescents: Position statement of the South African Thoracic Society - 2021 update.

Asthma prevalence is increasing worldwide, and surveys indicate that most patients in developed and developing countries, including South Africa, do not receive optimal care and are therefore not well controlled. Standard management guidelines adapted to in-country realities are important to support optimal care. The South African Thoracic Society (SATS) first published a guideline for the management of chronic persistent asthma in 1992, which has subsequently been revised several times. The main aim of the present document was to revise and update SATS' statement on the suggested management of chronic asthma, based on the need to promote optimal care and control of asthma, together with the incorporation of new concepts and drug developments. This revised document reinforces optimal care and incorporates the following primary objectives to achieve the recent advances in asthma care: continued emphasis on the use of inhaled corticosteroids (ICS) as the foundation of asthma treatmentto reduce the reliance on short-acting beta-2 agonist (SABA) monotherapy for asthma symptomsto incorporate the evidence and strategy for the use of the combination of an ICS and formoterol for acute symptom relief (instead of a SABA)to incorporate the evidence and strategy for the use of as-needed ICS-long-acting beta agonists (LABA) for patients with infrequent symptoms or 'mild' asthmato incorporate the evidence and strategy for the use of a long-acting muscarinic antagonist (LAMA) in combination with ICS-LABA; andto incorporate the evidence and strategy for the use of and management with a biologic therapy in severe asthma.

Subgingival Microbiota during Healthy Pregnancy and Pregnancy Gingivitis.

INTRODUCTION: Previous studies have largely explored the microbial composition and pathogenesis of pregnancy gingivitis. However, the patterns of microbial colonization during pregnancy in the absence of pregnancy gingivitis have rarely been studied. Characterization of the oral microbiome in pregnant women with healthy gingiva is an important initial step in understanding the role of the microbiome in progression to pregnancy gingivitis. OBJECTIVES: In this study, we compared the oral microbiome of pregnant women without gingivitis (healthy pregnancy) with pregnant women having gingivitis and nonpregnant healthy women to understand how pregnancy modifies the oral microbiome and induces progression to pregnancy gingivitis. METHODS: Subgingival plaque samples were collected from Chinese pregnant women with gingivitis (n = 10), healthy pregnant women (n = 10), and nonpregnant healthy women (n = 10). The Illumina MiSeq platform was used to perform 16S rRNA gene sequencing targeting the V4 region. RESULTS: The alpha and beta diversity was significantly different between pregnant and nonpregnant women, but minimal differences were observed between pregnant women with and without gingivitis. Interestingly, the oral bacterial community showed higher abundance of pathogenic taxa during healthy pregnancy as compared with nonpregnant women despite similar gingival and plaque index scores. However, when compared with overt pregnancy gingivitis, pathogenic taxa were less abundant during healthy pregnancy. PICRUSt analysis (phylogenetic investigation of communities by reconstruction of unobserved states) also suggested no difference in the functional capabilities of the microbiome during pregnancy, irrespective of gingival disease status. However, metabolic pathways related to amino acid metabolism were significantly increased in healthy pregnant women as compared with nonpregnant women. CONCLUSION: The presence of pathogenic taxa in healthy pregnancy and pregnancy gingivitis suggests that bacteria may be necessary for initiating disease development but progression to gingivitis may be influenced by the host environmental factors. More efforts are required to plan interventions aimed at sustaining health before the appearance of overt gingivitis. KNOWLEDGE TRANSFER STATEMENT: The results of this study draw attention to the importance of oral health maintenance during pregnancy, as women without any prenatal oral conditions are predisposed to the risk of developing pregnancy gingivitis. Hence, it is important to incorporate comprehensive assessment of oral health in the prenatal health care schedules. Pregnant woman should be screened for oral risks, counseled on proper oral hygiene and expected oral changes, and referred for dental treatment, when necessary.

Spiking Neural P Systems With Learning Functions.

Spiking neural P systems (SN P systems) are a class of distributed and parallel neural-like computing models, inspired from the way neurons communicate by means of spikes. In this paper, a new variant of the systems, called SN P systems with learning functions, is introduced. Such systems can dynamically strengthen and weaken connections among neurons during the computation. A class of specific SN P systems with simple Hebbian learning function is constructed to recognize English letters. The experimental results show that the SN P systems achieve average accuracy rate 98.76% in the test case without noise. In the test cases with low, medium, and high noises, the SN P systems outperform back propagation neural networks and probabilistic neural networks. Moreover, comparing with spiking neural networks, SN P systems perform a little better in recognizing letters with noise. The result of this paper is promising in terms of the fact that it is the first attempt to use SN P systems in pattern recognition after many theoretical advancements of SN P systems, and SN P systems exhibit the feasibility for tackling pattern recognition problems.

Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats.

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.

Organophosphate poisoning at Chris Hani Baragwanath Academic Hospital 2012 - 2015.

BACKGROUND: Patients with acute organophosphate poisoning are frequently admitted to the Chris Hani Baragwanath Academic Hospital (CHBAH), and yet there is little literature assessing aspects of these admissions. OBJECTIVES: To determine the demographic profile, common clinical and biochemical findings, use of prognostic tools (APACHE II), management and outcome of adult patients admitted to the high care area (HCA) and intensive care unit (ICU) at CHBAH. METHODS: A retrospective data analysis of hospital records for 129 patients admitted to the HCA and ICU at CHBAH for the period 2012 - 2015 was undertaken. The demographic profiles and clinical and biochemical presentations of the patients were determined, together with their subsequent management and outcomes. Use of the APACHE II score as a prognostic tool was evaluated, and the average enzyme inhibition levels demonstrated by the patients was assessed. RESULTS: The median age of the group was 30 years, with 68.2% being male. The most common clinical finding was pinpoint pupils (96.1%) followed by a Glasgow Coma Score <13 (85.3%), fasciculations (60.5%), diarrhoea (37.2%) and seizures (10.1%). Admissions to the HCA (52.7%) predominated, with the majority of patients requiring ventilator support (99.2%). The mean (SD) duration of stay was 6.8 days for ICU (6.4) and 3.7 days for HCA (5.2). The overall mortality rate was 5.4%. Standard treatment was intravenous atropine. Blood results reflected low levels of acetylcholinesterase enzyme activity. The APACHE II score was underutilised. CONCLUSION: The findings of the study underscore the frequent use of organophosphate compounds in our area. Further studies across the country will help to highlight the magnitude of the consequences of organophosphate poisoning, as well as the burden imposed on limited healthcare resources.

Evaluation of the knowledge and correct use of metered-dose inhalers by healthcare professionals and medical students in Gauteng Province.

BACKGROUND: The Global Initiative for Asthma (GINA) estimates that South Africa (SA) has over 3.9 million asthma sufferers, of whom 1.5% die of the condition annually. SA has the world's fourth highest asthma death rate among 5 - 35-year-olds. Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death globally by 2030, and will surpass HIV/AIDS in Africa. Uncontrolled asthma and COPD are frequent causes of emergency department visits and hospital admissions. Poor metered-dose inhaler (MDI) technique is probably a major contributory cause. It is the responsibility of all treating doctors and healthcare professionals to educate patients on inhaled therapy with the correct MDI technique, as well as to routinely check and repeatedly demonstrate the technique to them. OBJECTIVES: This study evaluated study participants' knowledge of MDI technique, and their compliance in checking and demonstrating MDI use to patients prescribed inhaled therapy. The study participants included doctors, nurses and final-year medical students at Helen Joseph Hospital and Chris Hani Baragwanath Academic Hospital, in the Departments of Internal Medicine and Emergency Medicine, and the Division of Pulmonology. METHODS: A total of 195 study participants volunteered to take part in the study. A questionnaire was administered to participants to gauge their perceptions, level of knowledge and understanding of MDI technique. They were then requested to demonstrate correct inhaler technique via a placebo MDI. Participants' use of a placebo MDI was evaluated by a scoring system. RESULTS: The total sample of 195 comprised 130 (67%) female and 65 (33%) male participants. Of these, 133 (68%) were qualified medical staff, and 62 were final-year medical students. Only 32 (16%) could demonstrate correct MDI technique. Over 50% of participants did not demonstrate MDI technique to patients, or check their patients' technique at every hospital-related visit. CONCLUSION: Healthcare professionals and final-year medical students have poor knowledge of inhaler technique and are ill-prepared to teach patients. Also of concern is that the majority do not routinely demonstrate or observe patients' inhaler technique.

Current status of Plasmodium knowlesi vectors: a public health concern?

Plasmodium knowlesi a simian malaria parasite is currently affecting humans in Southeast Asia. Malaysia has reported the most number of cases and P. knowlesi is the predominant species occurring in humans. The vectors of P. knowlesi belong to the Leucosphyrus group of Anopheles mosquitoes. These are generally described as forest-dwelling mosquitoes. With deforestation and changes in land-use, some species have become predominant in farms and villages. However, knowledge on the distribution of these vectors in the country is sparse. From a public health point of view it is important to know the vectors, so that risk factors towards knowlesi malaria can be identified and control measures instituted where possible. Here, we review what is known about the knowlesi malaria vectors and ascertain the gaps in knowledge, so that future studies could concentrate on this paucity of data in-order to address this zoonotic problem.

Histopathological diagnoses on pleural biopsy specimens over a 15-year period at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective review.

BACKGROUND: Pleural effusions are a common reason for presentation to healthcare facilities. Blind closed pleural biopsy can be a useful tool to diagnose their cause, especially in resource-limited settings. OBJECTIVES: To determine the aetiology, frequency and change in profile of histopathological diagnoses made at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over the period 1 January 2001 - 31 December 2015. METHODS: Pleural biopsies performed at CHBAH and analysed by histopathologists from the National Health Laboratory Service at the hospital over the study period were retrospectively reviewed by accessing reports from two databases (DISA and TrakCare). The subjects' ages, genders, HIV status and histopathological diagnoses as well as adenosine deaminase and Ziehl-Neelsen results were recorded. RESULTS: A total of 1 013 samples were included in the study, with 780 considered adequate for assessment. The most common diagnosis was granulomatous inflammation (48.1%, n=375), with the most common type being necrotising granulomatous inflammation (73.6%, n=276). Ten percent of biopsies (n=78) showed malignancy, most commonly adenocarcinoma, with 46.2% (n=36) metastatic and 23.1% (n=18) primary lung adenocarcinoma. The odds of being diagnosed with malignancy showed increasing statistical significance above the age of 40 years: 40 - 49 years odds ratio (OR) 8.7, 95% confidence interval (CI) 1.1 - 66.9 (p=0.038); 50 - 59 years OR 12.4, 95% CI 1.6 - 95.0 (p=0.015); ≥60 years OR 23.0, 95% CI 3.1 - 171.3 (p=0.002). HIV seropositivity was associated with lower odds of being diagnosed with malignancy compared with HIV-negative patients (OR 0.5, 95% CI 0.2 - 0.9; p=0.040), with greater odds of a 'non-cancer' diagnosis in HIV-positive patients (including granulomatous inflammation and pleuritis (OR 2.16, 95% CI 1.03 - 4.51; p=0.040)). CONCLUSIONS: Blind closed pleural biopsy has a role to play in the diagnosis of exudative pleural effusions in resource-limited settings, particularly for patients suspected to have tuberculosis (TB) or malignancy. TB remains a common cause of exudative pleural effusions. Patients aged >40 years presenting with an exudative pleural effusion should routinely have pleural biopsy performed. However, this study showed a high frequency of inadequate specimens from closed pleural biopsy. Training in the performance of this procedure to increase diagnostic rates is recommended.

Urinary Lipidomics: evidence for multiple sources and sexual dimorphism in healthy individuals.

Urinary lipidomics may add new valuable biomarkers to the diagnostic armamentarium for early detection of metabolic and kidney diseases. Sources and composition of urinary lipids in healthy individuals, however, have not been investigated in detail. Shotgun lipidomics was used to quantify lipidomic profiles in native urine samples from 16 individuals (eight men, eight women) collected in five fractions over 24 h. All probands were comprehensively characterized by urinary and clinical indices. The mean total urinary lipid concentration per sample was 0.84 µM in men and 1.03 µM in women. We observed significant intra- and interindividual variations of lipid concentrations over time, but failed to detect a clear circadian pattern. Based on quantity and subclass composition it seems very unlikely that plasma serves as major source for the urinary lipidome. Considering lipid metabolites occurring in at least 20% of all samples 38 lipid species from 7 lipid classes were identified. Four phosphatidylserine and one phosphatidylethanolamine ether species (PE-O 36:5) were detectable in almost all urine samples. Sexual dimorphism has been found mainly for phosphatidylcholines and phosphatidylethanolamines. In men and in women urinary lipid species were highly correlated with urinary creatinine and albumin excretion, reflecting glomerular filtration and tubular transport processes. In women, however, lipid species deriving from urinary cells and cellular constituents of the lower genitourinary tract considerably contributed to the urinary lipidome. In conclusion, our study revealed the potential of urinary lipidomics but also the complexity of methodological challenges which have to be overcome for its implementation as a routine diagnostic tool for renal, urological and metabolic diseases.

A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

Identifying data-driven subtypes of major depressive disorder (MDD) is an important topic of psychiatric research. Currently, MDD subtypes are based on clinically defined depression symptom patterns. Although a few data-driven attempts have been made to identify more homogenous subgroups within MDD, other studies have not focused on using human genetic data for MDD subtyping. Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data from MDD cases and controls using Hamming distance and cluster analysis. We examined a cohort of Mexican-American participants from Los Angeles, including MDD patients (n=203) and healthy controls (n=196). The results in cluster trees indicate that a significant latent subtype exists in the Mexican-American MDD group. The individuals in this hidden subtype have increased common genetic substrates related to major depression and they also have more anxiety and less middle insomnia, depersonalization and derealisation, and paranoid symptoms. Advances in this line of research to validate this strategy in other patient groups of different ethnicities will have the potential to eventually be translated to clinical practice, with the tantalising possibility that in the future it may be possible to refine MDD diagnosis based on genetic data.

The PHF21B gene is associated with major depression and modulates the stress response.

Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.