The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.
BackgroundNovel biomarkers are needed to assess response to antituberculosis therapy in smear-negative patients.MethodsTo evaluate the utility of C-reactive protein (CRP) in monitoring response to antituberculosis therapy, we conducted a post hoc analysis on a cohort of adults with symptoms of tuberculosis and negative sputum smears in a high–tuberculosis and HIV prevalence setting in KwaZulu-Natal, South Africa. Serial changes in CRP, weight, and hemoglobin were evaluated over 8 weeks.ResultsFour hundred twenty-one participants being evaluated for smear-negative tuberculosis were enrolled, and 33 were excluded. Two hundred ninety-five were treated for tuberculosis (137 confirmed, 158 possible), and 93 did not have tuberculosis. One hundred and eighty-three of 213 (86%) participants who agreed to HIV testing were HIV positive. At week 8, the on-treatment median CRP reduction in the tuberculosis group (interquartile range [IQR]) was 79.5% (25.4% to 91.7%), the median weight gain was 2.3% (−1.0% to 5.6%), and the median hemoglobin increase was 7.0% (0.8% to 18.9%); P < .0001 for baseline to week 8 comparison of absolute median values. Only CRP changed significantly at week 2 (median reduction [IQR], 75.1% [46.9% to 89.2%]) in the group with confirmed tuberculosis and in the possible tuberculosis group (median reduction [IQR], 49.0% [−0.4% to 80.9%]). Failure of CRP to reduce to ≤55% of the baseline value at week 2 predicted hospitalization or death in both tuberculosis groups, with 99% negative predictive value.ConclusionsChange in CRP may have utility in early evaluation of response to antituberculosis treatment and to identify those at increased risk of adverse outcomes.
Congenital disorders (CDs), defined as abnormalities in structure or function present at birth, are an important contributor to the disease burden in developing countries. The size and extent of the problem in South Africa (SA) are unknown due to the lack of recent, reliable, observed data on CDs. To address this empirical data gap, this study aimed to measure the birth prevalence of congenital anomalies (a sub-set of CDs) and to describe the pattern of these anomalies at a regional hospital in KwaZulu Natal (KZN), SA. A retrospective, observational, descriptive review of congenital anomalies diagnosed within the neonatal service at Edendale Hospital (EDH), KZN was undertaken between January and December 2018. All EDH in-house live births diagnosed and notified with congenital anomalies by discharge were included. Stillbirths, other pregnancy losses and out-born neonates were excluded. Data were actively collected from the birth register, neonatal admission register, and the individual paper-based surveillance tool developed by the National Department of Health. The in-facility birth prevalence rate for congenital anomalies was 15.57 per 1 000 live births. The most observed system was musculoskeletal (32%) followed by circulatory system anomalies (19%). When the observed birth prevalence rates of key congenital anomalies were compared with previously published, modelled South African data, no significant difference was found. This study responds to the paucity of birth prevalence data on CDs overall and offers evidence that obvious, structural CDs (congenital anomalies) need to be addressed in the SA public health system.
The elongated sigmoid colon seen in Black Africans is present in utero and occurs more frequently in Black African males. A narrow shape is more common in male foetuses and the broad shape is more common in female foetuses. These anatomical features may be the cause of the predisposition to sigmoid volvulus in Black African adults.
IntroductionLinkages between carbohydrates, obesity and cancer continue to demonstrate conflicting results. Evidence suggests inconclusive direct linkages between carbohydrates and specific cancers. Conversely, obesity has been strongly linked to a wide range of cancers. The purpose of the study is to explore linkages between carbohydrate intake and cancer types using a two-step approach. First the study will evaluate the linkages between carbohydrate intake and obesity, potentially stratified by metabolic syndrome status. Second, the estimated attributable fraction of obesity ascribed to carbohydrate intake will be multiplied against obesity attributable fractions for cancer types to give estimated overall attributable fraction for carbohydrate versus cancer type.Methods and analysisWe will perform a comprehensive search to identify all possible published and unpublished studies that have assessed risk factors for obesity including dietary carbohydrate intake. Scientific databases, namely PubMed MEDLINE, EMBASE, EBSCOhost and ISI Web of Science will be searched. Following study selection, paper/data acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, as well as assess heterogeneity. Meta-weighted attributable fractions of obesity due to carbohydrate intake will be estimated after adjusting for other potential confounding factors (eg, physical inactivity, other dietary intake). Furthermore, previously published systematic reviews assessing the cancer-specific risk associated with obesity will also be drawn. These estimates will be linked with the attributability of carbohydrate intake in part 1 to estimate the cancer-specific burden that can be attributed to dietary carbohydrates. This systematic review protocol has been developed according to the ‘Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015’.Ethics and disseminationThe current study will be based on published literature and data, and, as such, ethics approval is not required. The final results of this two part systematic review (plus multiplicative calculations) will be published in a relevant international peer-reviewed journal.Trial registration numberPROSPERO CRD42015023257.
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