A call to action: Temporal trends of COVID-19 deaths in the South African Muslim community

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Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa

Africa trails the rest of the world in COVID-19 cases and deaths. However, as the pandemic spreads through the continent, we expect increases in community infection in the months ahead. Patients with kidney infection, especially those with end-stage kidney disease and those with kidney transplants, are at high risk for acquiring the disease and dying from it. While there is limited evidence for the benefit of interventions, we have the advantage of learning from the experiences of those in China, Europe and the Americas. This document sets forth guidance for dealing with our patients who have acute and chronic kidney disease, including those on renal replacement therapy and the staff involved in their care. Emphasis is placed on preparedness and prevention strategies. As evidence and experience accumulate, it is likely that updated guidance will be needed.L’Afrique suit le reste du monde en termes de nombre de cas et de décès dus à COVID-19. Cependant, alors que la pandémie se propage à travers le continent, nous prévoyons une augmentation de l’infection communautaire dans les mois à venir. Les patients atteints d’une maladie rénale, en particulier ceux atteints d’une maladie rénale chronique en phase terminale et ceux ayant subi une transplantation rénale, courent un risque élevé de contracter la maladie et d’en mourir. Bien que les preuves d’interventions soient limitées, nous avons l’avantage de tirer des enseignements des expériences de ceux qui se trouvent en Chine, en Europe et dans les Amériques. Ce document présente des conseils pour traiter nos patients atteints d’insuffisance rénale aiguë et chronique, y compris ceux sous thérapie de suppléance rénale et le personnel impliqué dans leurs soins. L’accent est mis sur les stratégies de préparation et de prévention. Au fur et à mesure que les preuves et l’expérience s’accumulent, il est probable que des directives actualisées seront nécessaires

Correction: Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa

The authors of the article ‘Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa’ [1] wish to acknowledge the contribution of Professor Hussein El Fishawy. Our guidelines drew on various sources, including the Egyptian Ministry of Health guidelines, portions of which were adapted and reproduced with permission from the Egyptian Ministry of Health. Two of the authors of those guidelines, Professors Elsayed and Zaki, are also coauthors of our paper. Professor El Fishawy was the third author of the Egyptian guidelines and we would like to acknowledge his contribution to our review through this source, especially with respect to the treatment algorithms for patients with kidney transplants and those with acute kidney injury. Reference1. Elsayed HM, Wadee S, Zaki MS, Were AJO, Ashuntantang GE, Bamgboye EL, et al. Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa. Afr J Nephrol. 2020; 23(1):109-126

High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways

Neisseria gonorrhoeae Infection Induces Altered Amphiregulin Processing and Release

Adhesion of the human pathogen Neisseria gonorrhoeae has established effects on the host cell and evokes a variety of cellular events including growth factor activation. In the present study we report that infection with N. gonorrhoeae causes altered amphiregulin processing and release in human epithelial cells. Amphiregulin is a well-studied growth factor with functions in various cell processes and is upregulated in different forms cancer and proliferative diseases. The protein is prototypically cleaved on the cell surface in response to external stimuli. We demonstrate that upon infection, a massive upregulation of amphiregulin mRNA is seen. The protein changes its subcellular distribution and is also alternatively cleaved at the plasma membrane, which results in augmented release of an infection-specific 36 kDa amphiregulin product from the surface of human cervical epithelial cells. Further, using antibodies directed against different domains of the protein we could determine the impact of infection on pro-peptide processing. In summary, we present data showing that the infection of N. gonorrhoeae causes an alternative amphiregulin processing, subcellular distribution and release in human epithelial cervical cells that likely contribute to the predisposition cellular abnormalities and anti-apoptotic features of N. gonorrhoeae infections

The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin

Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses

The Kinetics of the Hydrogen/Deuterium Exchange of Epidermal Growth Factor Receptor Ligands

Five highly homologous epidermal growth factor receptor ligands were studied by mass spectral analysis, hydrogen/deuterium (H/D) exchange via attenuated total reflectance Fourier transform-infrared spectroscopy, and two-dimensional correlation analysis. These studies were performed to determine the order of events during the exchange process, the extent of H/D exchange, and associated kinetics of exchange for a comparative analysis of these ligands. Furthermore, the secondary structure composition of amphiregulin (AR) and heparin-binding-epidermal growth factor (HB-EGF) was determined. All ligands were found to have similar contributions of 310-helix and random coil with varying contributions of β-sheets and β-turns. The extent of exchange was 40%, 65%, 55%, 65%, and 98% for EGF, transforming growth factor-α (TGF-α), AR, HB-EGF, and epiregulin (ER), respectively. The rate constants were determined and classified as fast, intermediate, and slow: for EGF the 0.20 min−1 (Tyr), 0.09 min−1 (Arg, β-turns), and 1.88 × 10−3 min−1 (β-sheets and 310-helix); and for TGF-α 0.91 min−1 (Tyr), 0.27 min−1 (Arg, β-turns), and 1.41 × 10−4 min−1 (β-sheets). The time constants for AR 0.47 min−1 (Tyr), 0.04 min−1 (Arg), and 1.00 x 10−4 min−1 (buried 310-helix, β-turns, and β-sheets); for HB-EGF 0.89 min−1 (Tyr), 0.14 min−1 (Arg and 310-helix), and 1.00 x 10−3 min−1 (buried 310-helix, β-sheets, and β-turns); and for epiregulin 0.16 min−1 (Tyr), 0.03 min−1 (Arg), and 1.00 x 10−4 min−1 (310-helix and β-sheets). These results provide essential information toward understanding secondary structure, H/D exchange kinetics, and solvation of these epidermal growth factor receptor ligands in their unbound state

Platinum resistance in breast and ovarian cancer cell lines

Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade

Antidepressants and Breast and Ovarian Cancer Risk: A Review of the Literature and Researchers' Financial Associations with Industry

BACKGROUND: Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions. METHODS AND FINDINGS: We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03-1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012). CONCLUSIONS: Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the informed consent process