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BACKGROUND/AIM A study of patients in the Hubei Province, China, at the beginning of the pandemic demonstrated that among a group of 276 patients admitted to a hospital with laboratory-confirmed COVID-19, the proportion of patients who said they routinely wore eyeglasses more than 8 hours per day was lower than in the general population. Therefore, wearing eyeglasses more than 8 hours per day may be protective against SARS-CoV-2 infection, possibly because eyeglasses are a barrier that reduces the frequency with which people touch their eyes. The aim of the study was to determine if eyeglasses protect from COVID-19 infection. MATERIALS AND METHODS We used UK Biobank (UKB) data to corroborate findings of the Hubei study in the UK population. RESULTS Eyewear was associated with a reduced risk of infection, odds ratio (OR)=0.77. The effects of sex, age, and eyewear were independent and significant at the 95% level. Men are 1.24-times more likely to be infected than women; subjects' risk of infection is less (0.95) for every year of age. CONCLUSION The public at large may profit from wearing glasses, as well as wearing face masks and practicing social distancing.
Eyeglasses Reduce Risk of COVID-19 Infection.
Anxiety and uncertainty are common during pandemics. The present study extended previous pandemic research by investigating the role of two transdiagnostic risk factors anxiety sensitivity (AS: fear of physiological anxiety or fear of fear; Reiss & McNally, 1985) and intolerance of uncertainty (IU; Buhr & Dugas, 2009) in explaining relations between mental distress symptoms and behavioural responding during the COVID-19 pandemic. Student and community-based participants (N=457; 87.6% female) were recruited between May and July 2020 to complete measures of anxiety (health, panic, general), depression, and stress. Anxiety and related symptoms were found to be higher than in previous studies. Parallel mediation analyses showed that clinically meaningful levels of mental distress symptoms directly influenced safety behaviours and medical care utilization but also indirectly influenced the latter (vs. former) through AS-physical concerns (vs. IU). CBT interventions, targeting AS-physical concerns, may reduce mental distress symptoms during pandemic and prevent overuse of healthcare.
Anxiety Sensitivity Mediates Relations Between Mental Distress Symptoms and Medical Care Utilization During COVID-19 Pandemic
Over the last few years, dramatic increases in our knowledge about diffusely adhering Escherichia coli (DAEC) pathogenesis have taken place. The typical class of DAEC includes E. coli strains harboring AfaE-I, AfaE-II, AfaE-III, AfaE-V, Dr, Dr-II, F1845, and NFA-I adhesins (Afa/Dr DAEC); these strains (i) have an identical genetic organization and (ii) allow binding to human decay-accelerating factor (DAF) (Afa/Dr(DAF) subclass) or carcinoembryonic antigen (CEA) (Afa/Dr(CEA) subclass). The atypical class of DAEC includes two subclasses of strains; the atypical subclass 1 includes E. coli strains that express AfaE-VII, AfaE-VIII, AAF-I, AAF-II, and AAF-III adhesins, which (i) have an identical genetic organization and (ii) do not bind to human DAF, and the atypical subclass 2 includes E. coli strains that harbor Afa/Dr adhesins or others adhesins promoting diffuse adhesion, together with pathogenicity islands such as the LEE pathogenicity island (DA-EPEC). In this review, the focus is on Afa/Dr DAEC strains that have been found to be associated with urinary tract infections and with enteric infection. The review aims to provide a broad overview and update of the virulence aspects of these intriguing pathogens. Epidemiological studies, diagnostic techniques, characteristic molecular features of Afa/Dr operons, and the respective role of Afa/Dr adhesins and invasins in pathogenesis are described. Following the recognition of membrane-bound receptors, including type IV collagen, DAF, CEACAM1, CEA, and CEACAM6, by Afa/Dr adhesins, activation of signal transduction pathways leads to structural and functional injuries at brush border and junctional domains and to proinflammatory responses in polarized intestinal cells. In addition, uropathogenic Afa/Dr DAEC strains, following recognition of beta(1) integrin as a receptor, enter epithelial cells by a zipper-like, raft- and microtubule-dependent mechanism. Finally, the presence of other, unknown virulence factors and the way that an Afa/Dr DAEC strain emerges from the human intestinal microbiota as a "silent pathogen" are discussed.
Pathogenesis of Afa/Dr diffusely adhering Escherichia coli.
The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.
BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy
BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.
Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19
In this study, the antibiotic residue was used as a raw material to catalyze hydrothermal liquefaction (HTL) in an ethanol-water system to prepare bio-oil. The study explored the effects of ethanol-water ratio and three kinds of molecular sieve catalysts (HZSM-5, MCM-41, and ?3-Al2O3) on the yield and characterization of bio-oil. The experimental results showed that the highest bio-oil yield was obtained at the ethanol-water ratio of 1 : 1 and the three kinds of molecular sieve catalysts of 15%. GC-MS, 1H NMR, TGA, and CHNS were used for the characterization of bio-oil. Higher carbon (up to 71.44%), hydrogen (up to 9.376%), and a high heating value (HHV, 34.714 MJ kg-1) were observed for catalytically liquefied bio-oil compared to non-catalytically liquefied bio-oil. The analysis of aqueous phase products indicated the existence of valuable nutrients. Besides, the reusability of three kinds of molecular sieve catalysts indicated that catalysts could be successfully reused several times and continuously exhibited the catalyst effect.
Study on the hydrothermal liquefaction of antibiotic residues with molecular sieve catalysts in the ethanol-water system: focus on product distribution and characterization
OBJECTIVE: The global pandemic called COVID-19 has dragged the world into a healthcare crisis, and favipiravir is one of the most prescribed agents against the virus so far. Favipiravir is a repurposed antiviral agent in treatment of SARS-CoV-2 infection, and to meet the current need, pharmaceutical companies are working for manufacturing licensed generic favipiravir. For getting the marketing authorization, the bioequivalence of the generic product must be proven first. The aim of this study is to demonstrate the bioequivalence of a new favipiravir tablet formulation as compared to the reference tablet formulation in healthy male subjects under fasting conditions. MATERIALS AND METHODS: To prove the bioequivalence, a randomized, single oral dose, cross-over, two-period study was carried out in 30 healthy subjects under fasting conditions. Plasma favipiravir levels were quantified by using an in-house-developed high performance liquid chromatography with mass spectrometry detector (LC-MSD) method. RESULTS: The 90% CIs for the test/reference geometric mean ratios of the Cmax and AUC0-tlast were 88.02 - 103.11% and 98.19 - 102.06%, respectively. CONCLUSION: This single-dose study has shown that the test and reference favipiravir products met the required bioequivalence criteria. Besides, both products were well tolerated and safe.
Bioequivalence study of two favipiravir tablet formulations in healthy male subjects
From 11 March to 6 July 2020, a total of 268 imported cases of COVID-19 from abroad were confirmed in Guangzhou. 74% of the imported cases were detected during customs inspection and 19% under centralized quarantine. We advocate for legally enforced quarantine and monitoring of quarantined persons.
Countries of origin of imported COVID-19 cases into China and measures to prevent onward transmission?
BACKGROUND The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively. RESULTS We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers' and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV). CONCLUSIONS AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.
AutoCNV: a semiautomatic CNV interpretation system based on the 2019 ACMG/ClinGen Technical Standards for CNVs.
Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the En Balance-PLUS diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping. Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (?11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 10(?4), z-score = ?1.96), peroxidation of lipids (p = 2.24 10(?5), z-score = ?1.944), Ca(2+) transport (p = 1.55 10(?4), z-score = ?1.969), excitation of neurons (p = 1.07 10(?4), z-score = ?1.091), and concentration of glutathione (p = 3.06 10(?4), z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.
Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy
Coordinating humanitarian organizations in the procurement of urgently needed relief items is complex and characterized by decentralization and isolated decision-making The decentralized coordination of associated tasks often results in the duplication of efforts and redundant/incorrect relief items supplies into single disaster regions, having negative impacts on the most vulnerable ones This paper devotes attention to the challenges that exist in the coordination of procurement activities in relief supply chains and asks for improvement approaches to facilitate more efficient demand satisfaction in disaster situations Therefore, the authors apply multiple case study research including expert interviews with procurement agents and heads of logistics from international non-governmental organizations (NGOs), humanitarian start-ups and military logistics centers Results indicate that a lack of incentives to cooperate, poor communication, unclear division of competences and noncompliance to standards and regulations constitute substantial challenges in procurement coordination Moreover, expert interview results show that social media integration, procurement flexibility, cluster and collaborative coordination have potential to support improving the coordination of NGOs procurement activities By presenting several theoretical propositions, this paper complements already existing literature and provides a reference point for future research Practitioners can benefit from findings as they are provided with a guide that allows redesigning certain processes in procurement coordination
Identifying Challenges and Improvement Approaches for More Efficient Procurement Coordination in Relief Supply Chains
Time perception and prediction errors are essential for everyday life. We hypothesized that their putative shared circuitry in the striatum might enable these two functions to interact. We show that positive and negative prediction errors bias time perception by increasing and decreasing perceived time, respectively. Imaging and behavioral modeling identify this interaction to occur in the putamen. Depending on context, this interaction may have beneficial or adverse effects.
Prediction errors bidirectionally bias time perception.
We performed a time series analysis in Vienna, Austria, investigating the temporal association between daily air pollution (nitrogen dioxide, NO(2) and particulate matter smaller than 10 m, PM10) concentration and risk of coronavirus disease 2019 (COVID-19) infection and death. Data covering about 2 months (MarchCApril 2020) were retrieved from public databases. Infection risk was defined as the ratio between infected and infectious. In a separate sensitivity analysis different models were applied to estimate the number of infectious people per day. The impact of air pollution was assessed through a linear regression on the natural logarithm of infection risk. Risk of COVID-19 mortality was estimated by Poisson regression. Both pollutants were positively correlated with the risk of infection with the coefficient for NO(2) being 0.032 and for PM10 0.014. That association was significant for the irritant gas (p = 0.012) but not for particles (p = 0.22). Pollutants did not affect COVID-19-related mortality. The study findings might have wider implications on an interaction between air pollution and infectious agents.
COVID-19 and air pollution in Viennaa time series approach
As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.
A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration
Rutin (R), a representative flavonoid found in various biomasses, can be used to prepare different fluorescent sensors for environmental, biological and medical fields. In this work, the natural R in Sophora japonica was extracted and purified to prepare fluorescent-responding sensor systems intended to recognize copper ions with both strong selectivity as well as appropriate sensitivity. Results showed that neat R had no obvious fluorescent emission peak in PBS buffer solution. However, when R and (2-hydroxypropyl)--cyclodextrin (CD) were introduced within buffer solution, fluorescent emission intensity was significantly increased due to the resultant R-CD inclusion complex. In addition, the formed R-CD inclusion complex was shown to behave as the aforementioned fluorescent sensor for copper ions through a mechanism of quenched fluorescent emission intensity when R-CD became bound with copper ions. The binding constant value for R-CD with copper ions was 1.33 10(6), allowing for quantification of copper ions between the concentration range of 1.0 10(C7)C4.2 10(C6)mol?L(C1). Furthermore, the minimum detection limit was found to be 3.5 10(C8)mol?L(C1). This work showed the prepared R-CD inclusion complex was both highly selective and strongly sensitive toward copper ions, indicating that this system could be applied into various fields where copper ions are of concern.
Extraction and Application of Natural Rutin From Sophora japonica to Prepare the Novel Fluorescent Sensor for Detection of Copper Ions
We previously showed that infection of rat oligodendrocytes by ultraviolet light-inactivated mouse hepatitis virus (MHV) resulted in apoptosis, suggesting that the apoptosis is triggered during cell entry. To further characterize the earliest apoptotic signaling events, here we treated cells with an antibody specific to the MHV receptor prior to and during virus infection or with an antibody specific to MHV spike protein following virus binding. Both treatments blocked virus infection and apoptosis, indicating that virusCreceptor binding is necessary but not sufficient for the apoptosis induction. Furthermore, virus infection significantly increased the formation of the deathCreceptor complexes consisting of Fas, Fas-associated death domain and procaspase-8, but did not induce the complexes involving the tumor necrosis factor receptor and its associated death domain, demonstrating the specific activation of the Fas signaling pathway. Moreover, virus infection did not alter the abundance of the individual proteins of the complexes, suggesting that the activation of the Fas signaling pathway was at the post-translational level. Treatment with a Fas/Fc chimera, which blocks Fas-Fas ligand-mediated apoptosis, inhibited the formation of the complexes and blocked the activation of caspase-8 and apoptosis in MHV-infected cells. It also inhibited the release of cytochrome c from mitochondria and the activation of caspase-9. These results demonstrate that oligodendrocyte apoptosis is triggered by MHV infection during cell entry through the activation of the Fas signaling pathway.
Murine coronavirus-induced oligodendrocyte apoptosis is mediated through the activation of the Fas signaling pathway
[Figure: see text].
Web Exclusive. Annals Graphic Medicine - COVID Cataclysms: Coronavirus Through a Medical Student's Microscope
INTRODUCTION AND HYPOTHESIS: The use of new lightweight meshes in pelvic organ prolapse (POP) surgery may reduce complications related to mesh retraction (chronic pain, dyspareunia, and mesh exposure). The aim of this study was to investigate changes in the area and position of Uphold Lite™ mesh 6 weeks and 12 months after anterior and/or apical prolapse repair. METHODS: This observational prospective multicenter study included patients who had undergone transvaginal surgery for symptomatic POP-Q stage ≥ II anterior and/or apical compartment prolapse with placement of Uphold Lite mesh. The dimensions and position of the mesh were evaluated at 6 weeks and 12 months by ultrasonography. Correlations between ultrasonographic mesh characteristics and POP recurrence were analyzed. RESULTS: Fifty evaluable women with an average age of 66.8 years were included. No statistically significant difference in mesh area was found between week 6 and month 12 postoperatively, either at rest (1746.92 vs. 1574.48 mm2; p = 0.15) or on Valsalva (1568.81 vs. 1542.98 mm2; p = 0.65). The ROC-AUC of the distance between the mesh and the bladder neck (M-BN) at 6 weeks for predicting cystocele recurrence at 12 months was 0.764 (95% CI 0.573-0.955) at rest and 0.724 (95% CI 0.533-0.916) on Valsalva. An M-BN distance > 12.5 mm could predict cystocele recurrence at month 12 with a sensitivity of 80% and a specificity of 69%. CONCLUSIONS: Ultrasonographic measurements of the Uphold Lite™ mesh appear to remain stable between 6 weeks and 12 months postoperatively. M-BN distance correlates with cystocele recurrence. These results appear to confirm the value of ultrasound in mesh evaluation.
Prospective ultrasonographic follow-up of transvaginal lightweight meshes: a 1-year multicenter study
Rapidly growing evidence has now shown a high incidence of venous thrombosis in patients with severe acute respiratory syndrome secondary to novel coronavirus 2, a disease now named COVID-19. Accumulating case reports and series have also shown a higher prevalence of arterial thrombosis in these patients as well. Although the pathophysiology remains unknown but likely multifactorial C including endotheliitis from direct viral damage and an underlying hyper-inflammatory state, arterial and venous thrombosis occurrence does not appear to be linked with underlying classic risk factors for venous thromboembolism and may present in healthy patients without significant comorbidities. We present a case of a 22-year-old healthy patient with COVID-19 who developed a pulmonary embolism with a pulmonary infarction, a complication that results from arterial and venous thrombosis of the pulmonary vascular supply resulting in tissue necrosis.
A 22-year-old COVID-19 positive male with no prior medical history presented to the emergency department with pulmonary infarction
Background: The purpose of this paper was to describe the diagnosis, treatment and follow-up of patients diagnosed with congenital hypothyroidism (CH) by the Neonatal Screening Program in the Autonomous Community of Madrid during the state of alarm due to the COVID-19 health crisis Methods: The data were extracted from the retrospective analysis of patients diagnosed with CH and treated at the Clinical Diagnosis and Follow-up Center of CH located in the Pediatric Endocrinology Unit of the General University Hospital Gregorio Maranon Results: During the period between March 14 and June 21, 2020, 7 neonates were diagnosed with congenital hypothyroidism The Screening Center contacted the Clinical Diagnosis and Follow-up Center urgently, with the location and clinical assessment of the patient on the same day, performing the usual complementary examinations in all of them according to clinical pathway The median age of diagnosis was 15 5 days (range 7 00-24 00) The subsequent clinical and analytical follow-up was carried out in all cases according to the recommended times All patients presented normalization of the thyroid function after two weeks of treatment Conclusions: All patients seen at the Congenital Hypothyroidism Clinical Diagnosis and Follow-up Center during the alarm state period were diagnosed, treated and reevaluated following the usual clinical pathways without incidents The current epidemiological situation of the COVID-19 pandemic has revealed the correct functioning of the circuit of the Congenital Hypothyroidism Screening Program in less favorable circumstances
Impact of the COVID-19 pandemic on Neonatal Screening for Congenital Hypothyroidism

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