Allocation of scarce resources in Africa during COVID‐19: Utility and justice for the bottom of the pyramid?

The COVID‐19 pandemic has raised important universal public health challenges. Conceiving ethical responses to these challenges is a public health imperative but must take context into account. This is particularly important in sub‐Saharan Africa (SSA). In this paper, we examine how some of the ethical recommendations offered so far in high‐income countries might appear from a SSA perspective. We also reflect on some of the key ethical challenges raised by the COVID‐19 pandemic in low‐income countries suffering from chronic shortages in health care resources, and chronic high morbidity and mortality from non‐COVID‐19 causes. A parallel is drawn between the distribution of severity of COVID‐19 disease and the classic “Fortune at the bottom of the pyramid” model that is relevant in SSA. Focusing allocation of resources during COVID‐19 on the ‘thick’ part of the pyramid in Low‐to‐Middle Income Countries (LMICs) could be ethically justified on utilitarian and social justice grounds, since it prioritizes a large number of persons who have been economically and socially marginalized. During the pandemic, importing allocation frameworks focused on the apex of the pyramid from the global north may therefore not always be appropriate. In a post‐COVID‐19 world, we need to think strategically about how health care systems can be financed and structured to ensure broad access to adequate health care for all who need it. The root problems underlying health inequity, exposed by COVID‐19, must be addressed, not just to prepare for the next pandemic, but to care for people in resource poor settings in non‐pandemic times.     

Therapeutic potential of periodontal ligament stem cells

Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss. Due to the complexity of the periodontium, which is composed of several tissues, its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available. Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry, especially therapies using mesenchymal stem cells, as they can be isolated from a myriad of tissues. Periodontal ligament stem cells (PDLSCs) are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium. Biological insights have also highlighted PDLSCs as promising immunomodulator agents. In this review, we explore the state of knowledge regarding the properties of PDLSCs, as well as their therapeutic potential, describing current and future clinical applications based on tissue engineering techniques.     

A time course study on dose-response relationship between alcohol exposure and its effects on lipid profile and biomarkers of tissue damage

This present research investigated variations in lipid profiles and important biomarkers of tissue damage in response to graded concentrations of alcohol administration in male Wistar rats. Group A (control) received distilled water while group B, C and D received 30%, 40% and 50% (v/v) alcohol respectively. Five rats each from groups A-D were sacrificed after day(s) 1, 7, 14, 21 and 28 of administration. A significant increase was observed at day 28 for serum cholesterol by 79% (group B), 78% (group C) and 47% (group D) together with serum phospholipid 58% (group B), 50% (group C) and 92% (group D). Serum triacylglycerol increased by 71% (group B), 43% (group C) and 16% (group D) at day 21, while concentration of serum albumin decreased at day 28 by 40.9% (group B), 50.2% (group C), 53.3% (group D) respectively when compared with control (group A). Serum aminotransferases and alkaline phosphatase specific activities, as well as creatinine and uric acid concentration increased in a concentration-dependent manner, following alcohol administration. Though most of these effects induced by alcohol were time- and concentration-dependent, 40% alcohol appear to be more stable, giving results consistent with alcohol-induced damages, with minimal mortality. This study therefore further validated dyslipidemia and imbalance in clinical biomarkers as hallmarks of tissue damage induced by excessive alcohol consumption with an insight on the time- and concentration-response relationship between alcohol consumption and its toxicity.     

Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4

Background5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis.MethodsIL-4^+/+ or IL-4^?/? mice (25–30 g) were intraperitoneally injected with 5-FU (450 mg/Kg) or saline (C). After 3 days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration.Results5-FU induced significant damage in the intestinal epithelium of IL-4^+/+ mice (reduction in the villus/crypt ratio: control = 3.31 ± 0.21 μm, 5-FU = 0.99 ± 0.10 μm). However, the same treatment did not induce significant damage in IL-4^?/? mice (5-FU = 2.87 ± 0.19 μm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1β and CXCL-8) in the duodenum. These results were not observed in IL-4^?/? mice treated with 5-FU.ConclusionOur data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.     

Differential effects of cysteine and methionine residues in the antioxidant activity of human serum albumin

Antioxidant properties of human serum albumin (HSA) may explain part of its beneficial role in various diseases related to free radical attack. In the present study, the antioxidant role of Cys and Met was studied by copper-mediated oxidation of human low density lipoproteins and by free radical-induced blood hemolysis which essentially assessed metal-chelating and free radical scavenging activities, respectively. Mild conditions were set up to specifically modify Cys and Met residues by N-ethylmaleimide (NEM) and chloramine T treatments, respectively. We found that Met and Cys accounted for 40–80% of total antioxidant activity of HSA. Copper binding to HSA was decreased by about 50% with chloramine T treatment of Met whereas no change was observed after NEM treatment of Cys. Although other amino acid residues are likely to be involved in anti-/prooxidant properties of HSA, from our data, we propose that Cys chiefly works as a free radical scavenger whereas Met mainly acts as a metal chelator.     

Binding Interactions of Naringenin and Naringin with Calf Thymus DNA and the Role of β-Cyclodextrin in the Binding

The interaction of naringenin (Nar) and its neohesperidoside, naringin (Narn), with calf thymus deoxyribonucleic acid (ctDNA) in the absence and the presence of β-cyclodextrin (β-CD) was investigated. The interaction of Nar and Narn with β-CD/ctDNA was analyzed by using absorption, fluorescence, and molecular modeling techniques. Docking studies showed the existence of hydrogen bonding, electrostatic and phobic interaction of Nar and Narn with β-CD/DNA. 1:2 stoichiometric inclusion complexes were observed for Nar and Narn with β-CD. With the addition of ctDNA, Nar and Narn resulted into the fluorescence quenching phenomenon in the aqueous solution and β-CD solution. The binding constant K _b and the number of binding sites were found to be different for Nar and Narn bindings with DNA in aqueous and β-CD solution. The difference is attributed to the structural difference between Nar and Narn with neohesperidoside moiety present in Narn.     

Effects of bisphenol A on the microtubule arrays in root meristematic cells of Pisum sativum L.

Bisphenol A (BPA), a widely used chemical in the plastics industry that displays weak oestrogenic properties, is an emerging environmental pollutant, potentially harmful to living organisms. The presumed cytotoxicity of BPA to plant cells has been poorly studied. To understand how BPA might influence plant cell division and affect the underlying cytoskeleton, the effects of BPA on the microtubule (MT) arrays of meristematic root-tip cells of Pisum sativum L. were investigated. Root tips of young seedlings were exposed to 20, 50 and 100 mg/L BPA for 1, 3, 6, 12 and 24 h. The effects of each treatment were determined by means of confocal laser scanning microscopy after immunolabelling of tubulin and counterstaining of DNA, and by use of light and transmission electron microscopy. It was found that BPA affected normal chromosome segregation, hampered the completion of cytokinesis and deranged interphase and mitotic MT arrays. BPA effects were dependent on the stage of each cell at the time of BPA entrance. Moreover, BPA induced the formation of macrotubules with a mean diameter of 32 ± 0.14 nm, compared with 23 ± 0.70 nm for the MT arrays in untreated cells. Finally, all MT arrays and macrotubules were depolymerised upon longer treatment. Taken together, the data suggest that BPA exerts acute anti-mitotic effects on meristematic root-tip cells of P. sativum, MT arrays constitute a primary sub-cellular target of BPA toxicity, and the manifested chromosomal abnormalities could be attributed to the disruption of the MT cytoskeleton.     

Stability-Based Comparison of Class Discovery Methods for DNA Copy Number Profiles

Motivation

Array-CGH can be used to determine DNA copy number, imbalances in which are a fundamental factor in the genesis and progression of tumors. The discovery of classes with similar patterns of array-CGH profiles therefore adds to our understanding of cancer and the treatment of patients. Various input data representations for array-CGH, dissimilarity measures between tumor samples and clustering algorithms may be used for this purpose. The choice between procedures is often difficult. An evaluation procedure is therefore required to select the best class discovery method (combination of one input data representation, one dissimilarity measure and one clustering algorithm) for array-CGH. Robustness of the resulting classes is a common requirement, but no stability-based comparison of class discovery methods for array-CGH profiles has ever been reported.

Results

We applied several class discovery methods and evaluated the stability of their solutions, with a modified version of Bertoni''s -based test [1]. Our version relaxes the assumption of independency required by original Bertoni''s -based test. We conclude that Minimal Regions of alteration (a concept introduced by [2]) for input data representation, sim [3] or agree [4] for dissimilarity measure and the use of average group distance in the clustering algorithm produce the most robust classes of array-CGH profiles.

Availability

The software is available from http://bioinfo.curie.fr/projects/cgh-clustering. It has also been partly integrated into "Visualization and analysis of array-CGH"(VAMP)[5]. The data sets used are publicly available from ACTuDB [6].