Inhibition Effects and Mechanisms of Marine Compound Mycophenolic Acid Methyl Ester against Influenza A Virus.

Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.

Genomic characterization of SARS-CoV-2 in Guinea, West Africa.

SARS-CoV-2 has claimed several million lives since its emergence in late 2019. The ongoing evolution of the virus has resulted in the periodic emergence of new viral variants with distinct fitness advantages, including enhanced transmission and immune escape. While several SARS-CoV-2 variants of concern trace their origins back to the African continent-including Beta, Eta, and Omicron-most countries in Africa remain under-sampled in global genomic surveillance efforts. In an effort to begin filling these knowledge gaps, we conducted retrospective viral genomic surveillance in Guinea from October 2020 to August 2021. We found that SARS-CoV-2 clades 20A, 20B, and 20C dominated throughout 2020 until the coincident emergence of the Alpha and Eta variants of concern in January 2021. The Alpha variant remained dominant throughout early 2021 until the arrival of the Delta variant in July. Surprisingly, despite the small sample size of our study, we also found the persistence of the early SARS-CoV-2 clade 19B as late as April 2021. Together, these data help fill in our understanding of the SARS-CoV-2 population dynamics in West Africa early in the COVID-19 pandemic.

Spatial and Socioeconomic Inequalities in Cesarean Section Deliveries in Urban Settings in Dakar, Senegal.

As part of an initiative aimed at reducing maternal and child mortality, Senegal implemented a policy of free Cesarean section (C-section) since 2005. Despite the implementation, C-section rates have remained low and significant large disparities in access, particularly in major cities such as Dakar. This paper aims to assess C-section rates and examines socioeconomic inequalities in C-section use in the Dakar region between 2005 and 2019. This study incorporates data from various sources, including the health routine data within District Health Information Software 2 (DHIS2) platform, government statistics on slum areas, and data from Demographic and Health Surveys (DHS). A geospatial analysis was conducted to identify locations of Comprehensive emergency obstetric and Newborn Care (CEmONC) services using the Direction des Travaux Géographiques et Cartographiques (DTGC) databases and satellite imagery from the Google Earth platform. The analytical approach encompassed univariate, bivariate, and multivariate analyses. The C-section rate fluctuated over the years, increasing from 11.1% in 2005 to 16.4% in 2011, declined to 9.8% in 2014, and then raised to 13.3% in 2019. The wealth tertile demonstrated a positive correlation with C-sections in urban areas of the Dakar region. Geospatial analyses revealed that women residing in slum areas were less likely to undergo C-section deliveries. These findings underscore the importance of public health policies extending beyond merely providing free C-section delivery services. Strategies that improve equitable access to C-section delivery services for women across all socioeconomic strata are needed, particularly targeting the poor women and those in urban slums.

Genomic data integration tutorial, a plant case study.

BACKGROUND: The ongoing evolution of the Next Generation Sequencing (NGS) technologies has led to the production of genomic data on a massive scale. While tools for genomic data integration and analysis are becoming increasingly available, the conceptual and analytical complexities still represent a great challenge in many biological contexts. RESULTS: To address this issue, we describe a six-steps tutorial for the best practices in genomic data integration, consisting of (1) designing a data matrix; (2) formulating a specific biological question toward data description, selection and prediction; (3) selecting a tool adapted to the targeted questions; (4) preprocessing of the data; (5) conducting preliminary analysis, and finally (6) executing genomic data integration. CONCLUSION: The tutorial has been tested and demonstrated on publicly available genomic data generated from poplar (Populus L.), a woody plant model. We also developed a new graphical output for the unsupervised multi-block analysis, cimDiablo_v2, available at https://forgemia.inra.fr/umr-gdec/omics-integration-on-poplar , and allowing the selection of master drivers in genomic data variation and interplay.

Distribution and determinants of coronary artery calcium score in asymptomatic patients with Type-2 diabetes: The French-CAC100 score.

BACKGROUND: Coronary artery calcium score (CACS) refines the cardiovascular disease (CVD) risk prediction in patients with Type-2 diabetes (T2D). We aimed to identify the determinants for high CACS in CVD-free patients with T2D. METHODS: We studied 796 patients with T2D with CACS measured in three centers: two in continental France and a third in the Reunion Island. To predict a CACS ≥ 100, we derived a risk score in patients in continental France, and validated it in those in the Reunion Island. RESULTS: The distributions of CACS distributions were similar among patients in continental France and Reunion Island. The French-CAC100 score included 5 parameters (age, sex, diabetes duration, non-CV end-organ damage and presence of ≥ 2 other CVD risk factors), ranging from 0 to 22 points. Similar areas under the curves were found for the risk score in both settings (0.80 vs. 0.73, p = 0.10). A French-CAC100 score < 10 excluded the odds for CACS ≥ 100 and CACS ≥ 400 with negative predictive values of 90% and 97% respectively, avoiding 58% of CT-scans. CONCLUSION: Regardless of the geographic area, patients with T2D share similar risk factors for high CACS. The French-CAC100 score allows the identification of those at higher risk of elevated CACS.

Risk of amputation under diuretics in patients with or at risk of lower extremity arterial disease: A systematic review and meta-analysis.

BACKGROUND: Recently, increased risk of amputation under sodium glucose cotransporter-2 inhibitors has been debated. Similar concerns have been raised with other "traditional" diuretics, more particularly in patients with or at risk of lower extremity arterial disease (LEAD). AIM: To collect all available data on any potential risk of amputation associated with diuretics in patients with or at risk of LEAD. Additionally, we looked for other limb-related events in these patients. METHODS: We searched in PubMed, Embase and Scopus databases up to February 2021 for references, using peripheral or lower extremity arterial disease, diuretics and amputation keywords, excluding case reports, experimental animal studies and non-English reports. RESULTS: Among the 1376 hits identified in the databases, six studies were finally included in this review, including one cross-sectional and five longitudinal studies (total of 47,612 participants). One study was limited to thiazide diuretics, one focused on loop diuretics and the remainder mixed all diuretics. All studies reported a significant association between diuretic use and amputation risk in patients with or at high risk of LEAD. Despite some limitations in several studies, the meta-analysis showed an increased risk of amputation associated with diuretics (odds ratio: 1.75, 95% confidence interval: 1.53-1.99; P<0.001). Beyond amputation, patients with or at risk of LEAD under diuretics appeared to be at increased risk of other lower limb events, mostly in the presence of other comorbidities, including diabetes. CONCLUSIONS: Although the amount of data in the literature is scarce, this first systematic review and meta-analysis favours an increased risk of amputation in patients with or at risk of LEAD under diuretics. Further prospective studies must be conducted to provide a better understanding of the mechanisms. Meanwhile, the use of diuretics in these patients should be parsimonious, considering alternatives whenever possible.

Low impact of polyploidization on the transcriptome of synthetic allohexaploid wheat.

BACKGROUND: Bread wheat is a recent allohexaploid (genomic constitution AABBDD) that emerged through a hybridization between tetraploid Triticum turgidum (AABB) and diploid Aegilops tauschii (DD) less than 10,000 years ago. The hexaploidization can be re-created artificially, producing synthetic wheat that has been used to study immediate genomic responses to polyploidization. The scale of the consequences of polyploidization, and their mechanism of establishment, remain uncertain. RESULTS: Here we sampled several synthetic wheats from alternative parental genotypes and reciprocal crosses, and examined transcriptomes from two different tissues and successive generations. We did not detect any massive reprogramming in gene expression, with only around 1% of expressed genes showing significant differences compared to their lower-ploidy parents. Most of this differential expression is located on the D subgenome, without consistency in the direction of the expression change. Homoeolog expression bias in synthetic wheat is similar to the pattern observed in the parents. Both differential expression and homoeolog bias are tissue-specific. While up to three families of transposable elements became upregulated in wheat synthetics, their position and distance are not significantly associated with expression changes in proximal genes. DISCUSSION: While only a few genes change their expression pattern after polyploidization, they can be involved in agronomically important pathways. Alternative parental combinations can lead to opposite changes on the same subset of D-located genes, which is relevant for harnessing new diversity in wheat breeding. Tissue specificity of the polyploidization-triggered expression changes indicates the remodelling of transcriptomes in synthetic wheat is plastic and likely caused by regulome interactions rather than permanent changes. We discuss the pitfalls of transcriptomic comparisons across ploidy levels that can inflate the de-regulation signal. CONCLUSIONS: Transcriptomic response to polyploidization in synthetic AABBDD wheat is modest and much lower than some previous estimates. Homoeolog expression bias in wheat allohexaploids is mostly attributed to parental legacy, with polyploidy having a mild balancing effect.

Tracing 100 million years of grass genome evolutionary plasticity.

Grasses derive from a family of monocotyledonous plants that includes crops of major economic importance such as wheat, rice, sorghum and barley, sharing a common ancestor some 100 million years ago. The genomic attributes of plant adaptation remain obscure and the consequences of recurrent whole genome duplications (WGD) or polyploidization events, a major force in plant evolution, remain largely speculative. We conducted a comparative analysis of omics data from ten grass species to unveil structural (inversions, fusions, fissions, duplications, substitutions) and regulatory (expression and methylation) basis of genome plasticity, as possible attributes of plant long lasting evolution and adaptation. The present study demonstrates that diverged polyploid lineages sharing a common WGD event often present the same patterns of structural changes and evolutionary dynamics, but these patterns are difficult to generalize across independent WGD events as a result of non-WGD factors such as selection and domestication of crops. Polyploidy is unequivocally linked to the evolutionary success of grasses during the past 100 million years, although it remains difficult to attribute this success to particular genomic consequences of polyploidization, suggesting that polyploids harness the potential of genome duplication, at least partially, in lineage-specific ways. Overall, the present study clearly demonstrates that post-polyploidization reprogramming is more complex than traditionally reported in investigating single species and calls for a critical and comprehensive comparison across independently polyploidized lineages.

DNA hypomethylation of the host tree impairs interaction with mutualistic ectomycorrhizal fungus.

Ectomycorrhizas are an intrinsic component of tree nutrition and responses to environmental variations. How epigenetic mechanisms might regulate these mutualistic interactions is unknown. By manipulating the level of expression of the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1) and two demethylases DEMETER-LIKE (DML) in Populus tremula × Populus alba lines, we examined how host DNA methylation modulates multiple parameters of the responses to root colonization with the mutualistic fungus Laccaria bicolor. We compared the ectomycorrhizas formed between transgenic and wild-type (WT) trees and analyzed their methylomes and transcriptomes. The poplar lines displaying lower mycorrhiza formation rate corresponded to hypomethylated overexpressing DML or RNAi-ddm1 lines. We found 86 genes and 288 transposable elements (TEs) differentially methylated between WT and hypomethylated lines (common to both OX-dml and RNAi-ddm1) and 120 genes/1441 TEs in the fungal genome suggesting a host-induced remodeling of the fungal methylome. Hypomethylated poplar lines displayed 205 differentially expressed genes (cis and trans effects) in common with 17 being differentially methylated (cis). Our findings suggest a central role of host and fungal DNA methylation in the ability to form ectomycorrhizas including not only poplar genes involved in root initiation, ethylene and jasmonate-mediated pathways, and immune response but also terpenoid metabolism.

Perceptions of COVID-19 among communities of Conakry (Guinea): a qualitative study exploring the context of the ANRS COV33 Coverage-Africa therapeutic trial.

OBJECTIVES: To explore communities' perceptions about COVID-19 in the context of the ANRS COV33 Coverage-Africa clinical trial evaluating the efficacy of treatments in preventing clinical worsening of COVID-19. DESIGN: Descriptive qualitative study using semistructured in-depth individual interviews conducted by telephone in French and Soussou between May and September 2021. Data were transcribed, translated in French when applicable and analysed with the thematic analysis method. SETTING: The eight neighbourhoods most affected by COVID-19 in Conakry's urban context, capital of Guinea. PARTICIPANTS: 4 community leaders acting as key informants-providing insights regarding population's opinions-and six community members, who were exposed to an information session conducted as part of Coverage-Africa. RESULTS: According to participants, community members have heterogeneous viewpoints about COVID-19: it exists and is dangerous; it is benign ('bad cold'); or it is fictitious (eg, government conspiracy). The fear of stigmatisation and social isolation of those sick or cured of COVID-19 was largely reported by participants, with illustrations of distressing situations for the victims. To avoid stigma, many patients seem to adopt strategies of discretion (eg, lying/hiding about the disease). Although community attitudes were reported to have evolved since the beginning of the epidemic, stigma remained a pervasive concern for many people. CONCLUSIONS: Community perceptions about COVID-19 in Conakry may be partly explained by the Guinean context of Ebola history and of sociopolitical tensions. Stigmatisation of COVID+ people seems to be aimed at protecting others against contamination. However, social avoidance can greatly affect the morale of stigmatised people, especially in collectivist cultures like Guinea. Further investigating stigma, including its role on seeking COVID-19 screening and treatment services, and its consequences on mental health among affected/exposed people, would contribute to identifying improved prevention and care interventions in preparation for future health threats, and to promoting participation in health research. TRIAL REGISTRATION NUMBER: NCT04920838 (Pre-results stage).

Comparison of four equations for estimation of glomerular filtration rate in predicting cardiovascular events and subclinical vascular disease in patients with type-2 diabetes.

AIMS: Chronic kidney disease (CKD), defined by a low glomerular filtration rate (GFR), is a predictor of cardiovascular disease in patients with type-2 diabetes (T2D). We aimed to compare four GFR equations in predicting future cardiovascular events in T2D and the presence of subclinical vascular disease. METHODS: Four equations were used to estimate GFR in asymptomatic T2D patients consulting our centre for cardiovascular assessment. Follow-up was performed to collect cardiovascular events. Cox proportional hazard ratio (HR) was used to build and compare prediction models, and the incremental value of the addition of GFR with any of the 4 formulas was evaluated. The ability to triage patients with and without CVD events according to GFR were assessed by comparing the receiver operator characteristics (ROC) curves with the 4 models. RESULTS: Among 829 asymptomatic T2D patients, the CKD prevalence was 20.2% for Modification of Diet in Renal Disease (MDRD), 17.3% for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), 20.7% for Lund-Malmö Revised (LMR) and 21.4% for Full Age Spectrum (FAS). All the estimated GFRs were well correlated from one formula to another, with stronger agreement to define CKD (GFR <60 mL/min/1.73 m2) between MDRD and CKD-EPI, and between LMR and FAS. The 5-year incidence of cardiovascular events was 8% (n = 63). After adjustment on covariables, CKD was significantly associated with cardiovascular events when defined by MDRD (HR = 2.04; 1.15-3.60) and CKD-EPI (HR = 1.90; 1.05-3.41) but missed statistical significance when using LMR (HR = 1.74; 0.97-3.14) or FAS (HR = 1.71; 0.94-3.14). Only the prediction models including MDRD and CKD-EPI provided a significant incremental information to the predictive model without GFR, but the area under the ROC curves were similar with the 4 models: 0.60 [0.54-0.68] for MDRD, 0.61 [0.49-0.65] for CKD-EPI and 0.62 [0.55-0.69] for LMR and FAS, without any significant difference among formulas. CONCLUSION: In asymptomatic T2D patients, MDRD and CKD-EPI may be preferable when more specificity is desired (stronger association between GFR and CVD events), while LMR and FAS appear more sensitive by including a higher number of patients with GFR <60 mL/min/1.73 m2.

SARS-CoV-2 Circulation, Guinea, March 2020-July 2021.

This overview of severe acute respiratory syndrome coronavirus 2 circulation over 1.5 years in Guinea demonstrates that virus clades and variants of interest and concern were progressively introduced, mostly by travellers through Conakry, before spreading through the country. Sequencing is key to following virus evolution and establishing efficient control strategies.

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks.

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak-between 14 February and 19 June 2021-near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.

Rapid survey to determine the predictive factors of vaccination coverage in children aged 0 to 59 months in Guinea.

BACKGROUND: The Expanded Program on Immunisation has made it possible to prevent more than 3 million deaths in children under 5 years. The objectives of this study were to estimate the vaccination coverage of children from 0 to 59 months and identify factors associated with incomplete vaccination coverage. METHODS: A cross-sectional study was carried out in a dispensary in Conakry, Guinea between January and February 2020. Sociodemographic and vaccination information was collected from mothers of 380 randomly select children aged 0 to 59 months. Information on immunisation coverage was gathered from records vaccination cards and maternal reports. Logistic regression was used to identify factors independently associated with incomplete immunisation coverage. RESULTS: Most (66.5%) children aged < 12 months were up-to-date with their vaccinations. Factors associated with incomplete vaccination in this age group included: unavailability of vaccination cards (adjusted odds ratio [aOR] 7.58; 95% confidence interval [CI]: 2.56-22.44) and lack of prenatal consultation attendance (aOR 2.93; 95% CI: 1.15-7.48). In contrast only 19.8% (95% CI: 13.9-26.7) of children aged 12-59 months were fully immunised. Factors associated with incomplete vaccination coverage in children aged 12-59 months included high birth order (aOR 10.23; 95% CI: 2.06-19.43), and lack of prenatal consultation attendance (aOR 5.34; 95% CI: 1.48-19.23). CONCLUSION: Child immunisation coverage is low in Guinea. These results highlight the need to develop strategies based on an integrated approach to overcome obstacles to childhood immunisation in Guinea.

Peoples' attitude toward COVID-19 vaccine, acceptance, and social trust among African and Middle East countries.

Background: To end the COVID-19 pandemic, a large part of the world must be immune to the virus by vaccination. Therefore, this study aimed to gauge intent to be vaccinated against COVID-19 among ordinary people and to identify attitudes towards vaccines and barriers for vaccine acceptance. Methods: The study population comprises 1880 people residing in different countries that answer a prepared questionnaire. The questionnaire topics are demographics, historical issues, participants' attitudes and beliefs regarding vaccines, concerns, and vaccine hesitancy. Results: Attitudes and beliefs relating to vaccines in general, and the COVID-19 vaccine, were ascertained. Overall, 66.81% of the contributors would like to be vaccinated against COVID-19, while %33.19 did not intend to be vaccinated. Reasons for COVID-19 vaccine hesitancy included concern regarding vaccine side effects, fear of getting sick from the uptake of the vaccine, and the absence of accurate vaccine promotion news. Individuals with higher education believe that India (68.6%) produces the best vaccine (P <0.001), while healthcare workers think the Chinese vaccine (44.2%) is the best (P =0.020). Individuals with higher education have not been vaccinated, not be healthcare workers, and females were the most contributors to effective of the vaccine in reducing mortality from COVID-19 disease. Conclusion: Given the degree of hesitancy against COVID-19 vaccination, a multifaceted approach to facilitate vaccine uptake that includes vaccine education, behavioral change strategies, and health promotion, is paramount.

RNAi suppression of DNA methylation affects the drought stress response and genome integrity in transgenic poplar.

Trees are long-lived organisms that continuously adapt to their environments, a process in which epigenetic mechanisms are likely to play a key role. Via downregulation of the chromatin remodeler DECREASED IN DNA METHYLATION 1 (DDM1) in poplar (Populus tremula × Populus alba) RNAi lines, we examined how DNA methylation coordinates genomic and physiological responses to moderate water deficit. We compared the growth and drought response of two RNAi-ddm1 lines to wild-type (WT) trees under well-watered and water deficit/rewatering conditions, and analyzed their methylomes, transcriptomes, mobilomes and phytohormone contents in the shoot apical meristem. The RNAi-ddm1 lines were more tolerant to drought-induced cavitation but did not differ in height or stem diameter growth. About 5000 differentially methylated regions were consistently detected in both RNAi-ddm1 lines, colocalizing with 910 genes and 89 active transposable elements. Under water deficit conditions, 136 differentially expressed genes were found, including many involved in phytohormone pathways; changes in phytohormone concentrations were also detected. Finally, the combination of hypomethylation and drought led to the mobility of two transposable elements. Our findings suggest major roles for DNA methylation in regulation of genes involved in hormone-related stress responses, and the maintenance of genome integrity through repression of transposable elements.

Predictive factors of mortality in patients with COVID-19 in Guinea: analysis of the first 140 cases admitted to intensive care unit.

INTRODUCTION: the objective was to identify the predictive factors contributing to COVID-related deaths in Intensive Care Unit. METHODS: this was a 4-month (12th March to 12th July 2020) cross sectional study carried out in the intensive care unit of the COVID treatment center of Donka National Hospital, the only hospital with a COVID intensive care unit in Guinea. RESULTS: during our period of study 140 patients were hospitalized in the COVID intensive care unit and 35 patients died (25%). In univariate analysis, the occurrence of death was associated with: confusional syndrome (p<0.001), time to admission (p<0.001), use of an inotropic or vasopressor (p<0.001), Brescia score ≥ 2 (p=0.004), non-invasive ventilation (p=0.011), stroke (p=0.014), Acute Respiratory Distress Syndrome (ARDS) (p=0.015), male (p=0.021), provenance (p=0.021), acute renal failure (p=0.022), pulmonary embolism (p=0.022), invasive ventilation (p=0.022), and age > 60 years (p=0.047). In multivariate analysis, the factors predictive of mortality were: Acute Respiratory Distress Syndrome (ARDS) (OR= 6.33, 95% CI [1.66-29]; p=0.007), a Brescia score ≥ 2 (OR =5.8, 95% CI [1.7-19.2]; p=0.004) and admission delay (OR =5.6, 95% CI [1.8-17.5]; p=0.003). CONCLUSION: our study shows that the acute respiratory distress syndrome, then the Brescia score ≥ 2, and finally the time to admission to intensive care were all associated with an increased risk of death for patients. These results are different from those reported in Asia, Europe and North America.