Identification of phytochemical compounds of Fagopyrum dibotrys and their targets by metabolomics, network pharmacology and molecular docking studies.

Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.

Nonalcoholic Fatty Liver Disease Association with Intubation and Severity of Covid-19

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) and its hepatic manifestation, metabolic-associated fatty liver disease (MAFLD) have a rising prevalence worldwide in the background of the ongoing global pandemic. It is imperative to explore the relationship with COVID-19 to improve patient care and treatment protocols for better outcomes. This metaanalysis aims to investigate the association between NAFLD and MAFLD with the severity of COVID-19 infection and the need for mechanical ventilation. METHOD(S): A systematic review of literature across 5 databases was conducted from January 2019 to June 2022. Observational studies or clinical trials were included. Studies that evaluated NAFLD/ MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in Prospero and Prisma guidelines were followed (Figure 1). Meta-analysis was performed on studies with mechanical ventilation and severity of COVID-19 infection outcomes using Revman software. The Mantel- Haenszel odds ratio was generated to describe the overall effect size using random effect models. RESULT(S): Mechanical Ventilation A total of 36,817 patients from twelve studies were included in the qualitative analysis. There were 5615 patients in the NAFLD group and 31,202 patients in the Non-NAFLD group. A total of 3148 patients with COVID-19 required mechanical ventilation;778 (13.8%) in the NAFLD group and 782 (2.5%) in the Non-NAFLD group with high odds of need for mechanical ventilation (OR 2.03, 95%CI 1.06-3.88, p-value=0.03, I2=95%) (Figure 2). COVID-19 Severity A total of 5286 patients from fourteen studies were included in the qualitative analysis. 2716 patients were in the NAFLD group, while 2570 patients were in the Non-NAFLD group. A total of 1,623 patients had increased severity of COVID-19;901 (33.1%) in the NAFLD group and 722 (28.9%) in the Non-NAFLD group. COVID-19 patients with NAFLD had worse COVID-19 infection outcomes compared to those without NAFLD (OR 1.59, 95%CI 1.12-2.26, p-value=0.01, I2=81%) (Figure 4). CONCLUSION(S): Our meta-analysis suggests that NAFLD patients had higher odds of needing mechanical ventilation or ICU admission and developing more severe forms of COVID-19 than Non-NAFLD patients.

Clinical Manifestations and Disease Severity of Sars-Cov-2 Infection among Infants in Canada

BACKGROUND: There are limited data on outcomes of SARS-CoV-2 infection among infants (<1 year of age). In the absence of approved vaccines for infants, understanding characteristics associated with hospitalization and severe disease from COVID-19 in this age group will help inform clinical management and public health interventions. OBJECTIVE(S): The objective of this study was to describe the clinical manifestations, disease severity, and characteristics associated with hospitalization among infants infected with the initial strains of SARS-CoV-2. DESIGN/METHODS: This is a nationwide prospective observational study using the infrastructure of the Canadian Paediatric Surveillance Program. All cases of infants aged <1 year of age with microbiologically confirmed SARS-CoV-2 infection were reported from April 8th 2020 to May 31st 2021, and were classified by disease severity and primary cause of hospitalization. Multivariable logistic regression was performed to identify infants' characteristics associated with hospitalization. RESULT(S): A total of 531 cases were reported, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. Among hospitalized infants, 141 of 199 infants (70.9%) were admitted because of COVID-19-related illness, and 58 (29.1%) were admitted for reasons other than acute COVID-19. Amongst all cases with SARS-CoV-2 infection, the most common presenting symptoms included fever (66.5%), coryza (47.1%), cough (37.3%) and decreased oral intake (25.0%). In our main analysis, infants with a comorbid condition had higher odds of hospitalization compared to infants with no comorbid conditions, and infants <1 month had higher odds of hospitalization than infants aged 1-3 months (Table). In total, 20 infants (3.8%) met criteria for severe disease. CONCLUSION(S): We describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group is uncommon with most infants having mild disease. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants.

New-onset type 1 diabetes in children and adolescents before and during COVID-19 pandemic in Belgium

Introduction: Viral infections have been implicated in the development of type 1 diabetes. There have been reports of COVID-19 induced new-onset diabetes. Objective(s): In this context, this study aimed to describe and compare the characteristics at diagnosis of children who develop type 1 diabetes before and during the COVID-19 pandemic in Belgium. Method(s): This observational study compares two groups of children and adolescents who develop type 1 diabetes: the first includes newonset diabetes before the pandemic (1 March 2018 and 31 December 2019) and the second during the pandemic (1 March 2020 and 31 December 2021) in HUDERF, Brussels, Belgium. Result(s): In our center, the number of new-onset type 1 diabetes in the pre-pandemic period was 87 and in the pandemic period was 147 (p = 0.010). During the COVID-19 pandemic, patients with newonset diabetes were more often male (62% vs. 44%;p = 0.010) and had a slightly higher pH at admission [7.35 (7.22-7.41) vs. 7.34 (7.18- 7.38);p = 0.043] than before the pandemic. There was no difference in age, BMI SDS, HbA1c or severity of ketoacidosis at type 1 diabetes diagnosis. During the pandemic, 2 children (2%) had a positive SARSCoV2 PCR test on admission but were asymptomatic. Conclusion(s): The number of new cases of type 1 diabetes in our center during the COVID-19 pandemic was significantly higher than before the pandemic. These new patients were mainly male. Longerterm and national follow-up is needed to assess the role of COVID-19 in the development of type 1 diabetes.

Oleic acid-induced acute lung injury in Ob/Ob mice fed with high-fat-diet exacerbate bile acid uptake and liver injury that was reversed by antagonizing their entry

Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.

Creation and Implementation of Virtual Urogynecology Patient Cases for Medical Student Education.

Introduction: Urogynecologic disorders are highly prevalent, and many physicians across various specialties will encounter and care for patients with pelvic floor disorders. Yet most medical students have had limited to no experience in diagnosing and managing pelvic floor disorders, resulting in a gap in clinical education. Methods: Three virtual and interactive urogynecologic patient cases were developed on an e-learning platform with an overall goal of increasing clinical exposure to various pelvic floor disorders. The cases were integrated into the medical student obstetrics and gynecology clerkship during the 2020-2021 academic year (n = 40). Participants provided feedback regarding usability, acceptability, and educational value of the cases. Results: Twenty-one students (52%) completed the survey. Ninety percent (n = 19) agreed or strongly agreed that they were satisfied with the cases, and 71% (n = 15) agreed or strongly agreed that they would recommend the virtual patient cases to other students. All students (n = 21) felt that the format was easy to use and reported that the cases were appropriate for their level of learning. Most students felt that the cases increased or significantly increased their confidence regarding nonsurgical and surgical management options for pelvic floor disorders. Discussion: Our findings suggest that these interactive virtual patient cases are an acceptable, valuable, and effective tool for learners. Utilizing the cases can help mitigate existing disparities in exposure to pelvic floor disorders both highlighted by and preceding the COVID-19 pandemic.

Impact of the COVID-19 Pandemic on Obstetricians/Gynecologists.

OBJECTIVE: To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on obstetricians/gynecologists (OB/GYNs). PARTICIPANTS AND METHODS: A 49-item survey was distributed to OB/GYNs through the websites and electronic mailing lists of professional OB/GYN organizations. The survey was open from June 22, 2020, through November 22, 2020. Of the 122 initiated surveys, 89 were completed (73.0% completion rate); 72 respondents answered at least one open-ended question and were included for qualitative analysis. RESULTS: Respondents reported policy changes, limited personal protective equipment availability, patient compliance with safety protocols and personal protective equipment use, staff shortages, and concerns about COVID-19 exposure as primary stressors related to the pandemic. Respondents felt that the pandemic had a negative professional impact on their relationships with patients and colleagues. Workplace and pandemic stressors resulted in feelings of anxiety and frustration; physical effects were also reported. Some respondents indicated that they were considering early retirement or leaving the profession as a result of the pandemic, which suggests that OB/GYNs may be at increased risk for burnout. CONCLUSION: The COVID-19 pandemic will have important long-term effects on OB/GYN well-being and workforce retention. Proactive support for OB/GYNs is needed to combat burnout and counteract workforce attrition. Implementing peer support programs that promote healthy emotional processing following adverse events may mitigate these feelings and reduce OB/GYN burnout.

Artificial intelligence in clinical care amidst COVID-19 pandemic: A systematic review.

The worldwide health crisis caused by the SARS-Cov-2 virus has resulted in>3 million deaths so far. Improving early screening, diagnosis and prognosis of the disease are critical steps in assisting healthcare professionals to save lives during this pandemic. Since WHO declared the COVID-19 outbreak as a pandemic, several studies have been conducted using Artificial Intelligence techniques to optimize these steps on clinical settings in terms of quality, accuracy and most importantly time. The objective of this study is to conduct a systematic literature review on published and preprint reports of Artificial Intelligence models developed and validated for screening, diagnosis and prognosis of the coronavirus disease 2019. We included 101 studies, published from January 1st, 2020 to December 30th, 2020, that developed AI prediction models which can be applied in the clinical setting. We identified in total 14 models for screening, 38 diagnostic models for detecting COVID-19 and 50 prognostic models for predicting ICU need, ventilator need, mortality risk, severity assessment or hospital length stay. Moreover, 43 studies were based on medical imaging and 58 studies on the use of clinical parameters, laboratory results or demographic features. Several heterogeneous predictors derived from multimodal data were identified. Analysis of these multimodal data, captured from various sources, in terms of prominence for each category of the included studies, was performed. Finally, Risk of Bias (RoB) analysis was also conducted to examine the applicability of the included studies in the clinical setting and assist healthcare providers, guideline developers, and policymakers.

Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study.

BACKGROUND: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2. METHODS: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information. FINDINGS: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05). INTERPRETATION: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2. FUNDING: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.

Dataset of potential Rhizoma Polygonati compound-druggable targets and partial pharmacokinetics for treatment of COVID-19.

Rhizoma Polygonati (Chinese name as , pinyin as huangjing), as medicine and food homology of Traditional Chinese Medicine, has been recently applied for the complex prescriptions of alternative medicine for treatment of COVID-19 but the mechanisms are largely unclear. Here using public database search and filtering the potential chemical compound based drug targets with COVID-19 targets mapped, the list of data were provided and suggested pharmacokinetic tolerating dose of selected natural compounds were further collected from database. The data provided is the supplementary as a reference showing the intersections of Rhizoma Polygonati druggable targets of lists from current database and potentially related ones targeting COVID-19.

The COVID-19 pandemic and patients with endometriosis: A survey-based study conducted in Turkey.

OBJECTIVE: To apply rapid online surveying to determine the knowledge and perceptions of the COVID-19 pandemic on patients with endometriosis in Turkey. METHODS: An online survey was conducted by the Turkish Endometriosis & Adenomyosis Society and administered to patients with endometriosis who agreed to participate in the study. The survey included 25 questions prepared by an expert committee of four professionals (two gynecologists and two endometriosis specialists). RESULTS: Of the 290 questionnaires sent out, 261 (90%) were returned. A total of 213 (83.86%) patients reported that they were afraid of having endometriosis-related problems during the pandemic period. In addition, 133 (53.63%) patients thought the management of their endometriosis was affected because of the pandemic. CONCLUSION: Clinical studies clearly indicate that endometriosis is a condition associated with high levels of chronic stress. The COVID-19 pandemic has led the public to experience psychological problems such as post-traumatic stress disorder, psychological distress, depression, and anxiety. The majority of patients with endometriosis were afraid of having endometriosis-related problems during the pandemic period. The majority of elective endometriosis surgeries have not been postponed. Patients were highly aware of the pandemic and practiced social distancing and hygiene. Only 4 (1.59%) patients with endometriosis required hospitalization.

Managing an obstetrics and gynaecology department in time of COVID pandemic: safety and efficacy first at Foch hospital.

Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.

Effective Use of Virtual Gamification During COVID-19 to Deliver the OB-GYN Core Curriculum in an Emergency Medicine Resident Conference.

Introduction Coronavirus disease 2019 (COVID-19) has challenged medical educators on continuing to provide quality educational content in a virtual setting. The objective of this module was to create a gamified review of core obstetric and gynecology (OB-GYN) topics that residents would find educational and informative. Methods The game created was modeled after the TV show "So You Think You Can Dance?", with a warm-up and several rounds of rapid-fire OB-GYN questions and cases, eliminating teams to a final face-off. The residents were given a post-session survey to determine their attitudes and learning towards this virtual conference approach. Results Based on the post-session survey, the majority of the residents found this activity to be educational, entertaining, engaging, and better than the traditional lecture format. Conclusion This initial attempt at migrating gamification, a core component of our live conferences, into the new virtual arena, was well-received by learners as effective, educational, and engaging. This style of gamification can be incorporated into residency programs at other institutions currently limited to virtual platforms to boost resident education and engagement.