Co-Incidence of Epstein–Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis

Association between pre-existing conditions and hospitalization, intensive care services and mortality from COVID-19 - a cross sectional analysis of an international global health data repository

Objective: To investigate the association between pre-existing conditions and hospitalization, need for intensive care services (ICU) and mortality due to COVID-19. Methods: We used data on all cases recorded in the Global Health Data repository up to the 10th of March 2021 to carry out a cross-sectional analysis of associations between cardiovascular diseases (CVD), hypertension, diabetes, obesity, lung diseases and kidney disease and hospitalization, ICU and mortality due to COVID-19. We included data from Brazil, Mexico and Cuba only as they were the only countries where preexisting conditions were reported. We used multivariable logistic regression to compute adjusted and unadjusted odds ratios (OR) of the three outcomes for each pre-existing condition in ten-year age groups from 0-9 years and up to 110-120 years. Results: As of the 10th of March 2021, the Global Health repository held 25 900 000 records of confirmed cases of COVID-19, of which 2 900 000 cases from Brazil, Mexico and Cuba had data on preexisting conditions. The overall adjusted odds of hospitalization for each pre-existing condition were; CVD (OR 1.7, 95%CI 1.7-1.7), hypertension (OR 1.5, 95%CI 1.4-1.5), diabetes (OR 2.2, 95%CI 2.1-2.2), obesity (OR 1.7, 95%CI 1.6-1.7), kidney disease (OR 5.5, 95%CI 5.2-5.7) and lung disease (OR 1.9, 95%CI 1.8-1.9). The overall adjusted odds of ICU for each pre-existing condition were; CVD (OR 2.1, 95%CI 1.8-2.4), hypertension (OR 1.3, 95%CI 1.2-1.4), diabetes (OR 1.7, 95%CI 1.5-1.8), obesity (OR 2.2, 95%%CI 2.1-2.4), kidney disease (OR 1.4, 95%CI 1.2-1.7) and lung disease (OR 1.1, 95%CI 0.9-1.3). The overall adjusted odds of mortality for each pre-existing condition were; CVD (OR 1.7, 95%CI 1.6-1.7), hypertension (OR 1.3, 95%CI 1.3-1.4), diabetes (OR 2.0, 95%CI 1.9-2.0), obesity (OR 1.9, 95%CI 1.8-2.0), kidney disease (OR 2.7, 95%CI 2.6-2.9) and lung disease (OR 1.6, 95%CI 1.5-1.7). The odds of each outcome were considerably larger in children and young adults with these preexisting conditions than for adults, especially for kidney disease, CVD and diabetes. Conclusion: Individuals with CVD, hypertension, diabetes, obesity, lung diseases and kidney diseases have high odds of hospitalization, ICU and mortality from COVID-19. The odds of these outcomes are especially elevated in children and young adults with these preexisting condition

Mitotic Arrest-Deficient 2 Like 2 (MAD2L2) Interacts with Escherichia coli Effector Protein EspF

Enteropathogenic (EPEC) and Enterohemorrhagic (EHEC) Escherichia coli are considered emerging zoonotic pathogens of worldwide distribution. The pathogenicity of the bacteria is conferred by multiple virulence determinants, including the locus of enterocyte effacement (LEE) pathogenicity island, which encodes a type III secretion system (T3SS) and effector proteins, including the multifunctional secreted effector protein (EspF). EspF sequences differ between EPEC and EHEC serotypes in terms of the number and residues of SH3-binding polyproline-rich repeats and N-terminal localization sequence. The aim of this study was to discover additional cellular interactions of EspF that may play important roles in E. coli colonization using the Yeast two-hybrid screening system (Y2H). Y2H screening identified the anaphase-promoting complex inhibitor Mitotic Arrest-Deficient 2 Like 2 (MAD2L2) as a host protein that interacts with EspF. Using LUMIER assays, MAD2L2 was shown to interact with EspF variants from EHEC O157:H7 and O26:H11 as well as EPEC O127:H6. MAD2L2 is targeted by the non-homologous Shigella effector protein invasion plasmid antigen B (IpaB) to halt the cell cycle and limit epithelial cell turnover. Therefore, we postulate that interactions between EspF and MAD2L2 serve a similar function in promoting EPEC and EHEC colonization, since cellular turnover is a key method for bacteria removal from the epithelium. Future work should investigate the biological importance of this interaction that could promote the colonization of EPEC and EHEC E. coli in the host

Co-Incidence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women.

Epstein-Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.We would like to thank Mrs. A. Kassab for her critical reading of the manuscript. This work was supported by Qatar University grants # GCC-2017-002 QU/KU and QUCG-CMED-2018\2019-3

Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016)

La diseminación mundial de Staphylococcus aureus resistente a meticilina (SARM) está asociada a la aparición y el establecimiento de clones en zonas geográficas específicas. El clon chileno-cordobés (ChC) (ST5-SCCmecI) ha sido el clon de SARM predominante en Chile desde su primera descripción en 1998, a pesar del informe de otros clones de SARM emergentes en los últimos años. Aquí, caracterizamos la historia evolutiva de MRSA desde 2000 hasta 2016 en un centro de salud terciario chileno utilizando análisis filogenómicos. Secuenciamos 469 aislamientos de SARM recogidos entre 2000 y 2016. Evaluamos las tendencias temporales de los clones circulantes y realizamos una reconstrucción filogenómica para caracterizar la dinámica clonal. Encontramos un aumento significativo en la diversidad y riqueza de tipos de secuencia (STs; Spearman r = 0,8748, P , 0,0001) con un índice de diversidad de Shannon que aumentó de 0,221 en el año 2000 a 1,33 en 2016, y una diversidad efectiva (número de Hill; q = 2) que aumentó de 1,12 a 2,71. El análisis de la tendencia temporal reveló que en el periodo de 2000 a 2003 la mayoría de los aislados (94,2%; n = 98) pertenecían al clon ChC. Sin embargo, desde entonces, la frecuencia del clon ChC ha disminuido con el tiempo, representando el 52% de la colección en el período de 2013 a 2016. Este descenso estuvo acompañado por el aumento de dos linajes emergentes de SARM, ST105-SCCmecII y ST72-SCCmecVI. En conclusión, el clon ChC sigue siendo el linaje MRSA más frecuente, pero este linaje está siendo reemplazado gradualmente por varios clones emergentes, el más importante de los cuales es el clon ST105-SCCmecII. Hasta donde sabemos, éste es el mayor estudio de la dinámica clonal del SARM realizado en Sudamérica. © 2023 Martínez et al.The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P , 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. © 2023 Martínez et al

Dynamics of the Mrsa Population in a Chilean Hospital: a Phylogenomic analysis (2000-2016)

The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P \u3c 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. to the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCmecII and ST72-SCCmecVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America

Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe