title: Bracing for impact: operational upshots from the National Centre for Infectious Diseases Screening Centre (Singapore) during the COVID‐19 outbreak

text: To combat the ongoing COVID‐19 pandemic, Singapore has adopted a rigorous screening approach that involves aggressive contact tracing, rapid isolation of confirmed or suspect cases, and immediate ring‐fencing of emerging local clusters and hotspots. Our screening centre team has been involved in running Singapore's designated screening centre since the end of January this year. With a well‐defined blueprint and substantial pre‐outbreak preparatory work, initial operations at our screening centre commenced within a day on activation and full operational status was attained in 3 days. As of 8 April 2020, the screening centre had screened more than 14,000 patients. We have adopted a “whole‐of‐hospital” approach, enlisting the help from other departments and subspecialties to augment manpower. Meticulous infrastructure planning to facilitate patient flow and strict measures to prevent nosocomial transmission and occupational exposure were instituted to safeguard both the staff and patients. This paper aims to describe our key takeaways in the course of operations and discuss the challenges encountered.


docid: zxrgkhmr

title: Interleukin-35 as an Emerging Player in Tumor Microenvironment

text: IL-35 is the newest member of IL-12 family. A dimeric protein consisting of two separate subunits has manifested suppressive actions on immune system, which is counterproductive in the context of cancers. Various reports have confirmed its inhibitory role on immune system which is carried out via formation of IL-35-producing regulatory T cells (iTr35), increased Treg development and suppressive Th17 cells growth. Although last decade has seen a great deal of scientific interest on this subject, the exact role, precise signal transduction and elaborative functions of IL-35 in tumor microenvironment (TME) remained elusive. Search for anti-IL-35 therapies have exhibited limited success in animal models. Contrarily, few studies have denied the idea that IL-35 plays a role in cancer. The purpose of this review is to analyze the reported scientific data on continuous symphony of IL-35 in cancers since the inception of former.


docid: jsrykwnf

title: Q & A

text: Victorian corpse displays sparked John Troyer's interest in how humans use technology around dead bodies. He explores our fascination with death and its impact on life


title: Microbiologic Methods in the Diagnostics of Upper Respiratory Tract Pathogens

text: Upper respiratory tract infection (URI) is a nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx above the vocal cords. The aim of this study was to provide a summary of the most common pathogens of URI and to compare advantages and disadvantages of traditional and new rapid microbiological tests used to identify them. Blood samples were simultaneously examined by the enzyme-linked immunosorbent assay (ELISA) and by the FilmArray Respiratory Panel for eight different pathogens in a total of 15 tests performed in nasopharyngeal swabs. The ELISA method is unable to identify the pathologic agent until the host’s immune system elicits a response. The method is readily available in many laboratories at a low cost, which puts less strain on economic resources. The FilmArray(®) Panel, on the other hand, is more expensive, but it is fast and exact in the identification of a broad spectrum etiologic agents. Nonetheless, since most repiratory tract infections are viral in origin and there is no treatment available, the diagnosis provided by the FilmArray Panel does not provide any additional clinical benefit and thus should be used only whenever necessary on the individual basis.


title: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy

text: Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.


title: Effects of forced air warming systems on the airflow and sanitation quality of operating rooms with non-laminar airflow systems

text: BACKGROUND: : Previous studies have demonstrated that forced air warming (FAW) can be used safely in operating rooms with laminar airflow (LAF) ventilation systems. However, the effects of FAW on the airflow at surgical sites under non-LAF (nLAF) ventilation systems remain unclear, as nLAF systems generate outlet-to-inlet multidirectional airflows of the air conditioning system. Here, we evaluate the effects of FAW on the airflow and sanitation quality in surgical fields with nLAF ventilation systems. METHODS: : The airflow speed and direction were measured using a three-dimensional ultrasonic anemometer. Sanitation quality was evaluated by measuring the amount of dust particles after the activation of air conditioning. RESULTS: : FAW caused no meaningful airflow (> 10 cm/sec) and did not diminish the sanitation quality in the surgical field separated by the anesthesia screen. Above the head area, the upward FAW airflow was not counteracted by nLAF, which caused an upward airflow at the edges of the operating table, originating from outside of the operating table and the floor. CONCLUSIONS: : Sanitation quality was kept under FAW working even in an nLAF-equipped OR. According to the inlet/outlet layouts of nLAF, the upward FAW-induced airflow in the head area was not counteracted, and the upward airflow from the floor induced by the air conditioner outlet could be detected.


title: Recombinant nucleocapsid protein-based IgG enzyme-linked immunosorbent assay for the serological diagnosis of SARS

text: Abstract The recombinant nucleocapsid protein (rNP) of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) was expressed in a baculovirus system. The purified SARS-CoV rNP was used as an antigen for detection of SARS-CoV antibodies in IgG enzyme-linked immunosorbent assay (ELISA). The ELISA was evaluated in comparison with neutralizing antibody assay and the authentic SARS-CoV antigen-based IgG ELISA. Two-hundred and seventy-six serum samples were collected from health care workers in a hospital in which a nosocomial SARS outbreak took place and used for evaluation. The SARS-CoV rNP-based IgG ELISA has 92% of sensitivity and specificity compared with the neutralizing antibody assay and 94% sensitivity and specificity compared with the authentic SARS-CoV antigen-based IgG ELISA. The results suggest that the newly developed SARS-CoV rNP-based IgG ELISA is a valuable tool for the diagnosis and seroepidemiological study of SARS. The SARS-CoV rNP-based IgG ELISA has an advantage over the conventional IgG ELISA in that the antigen can be prepared by laboratory workers without the risk of infection.


Leukoerythroblastic reaction in a patient with COVID‐19 infection


title: Imported and locally transmitted mild SARS-CoV-2 pneumonia cases in Japan

text: Abstract Here, we describe two mild SARS-CoV-2 pneumonia cases. One was imported from Wuhan, and the other was locally transmitted in Japan without recent travel to China. In both cases, lower respiratory tract symptoms were observed first, and high fever progressed in about one week. The laboratory findings revealed normal WBC and CRP despite apparent lung infiltrations, and typical observations on CT imaging were important diagnostic clues. In the domestic endemic situation, a comprehensive evaluation of the clinical course, and laboratory and radiological findings was required for diagnosis.


Measures to Prevent Healtcare Workers from Contracting Severe Acute Respiratory Syndrome During High-Risk Surgical Procedures


title: Abnormal liver tests in patients hospitalized with Coronavirus disease 2019: should we worry?

text: While several studies from China have reported COVID‐19‐related liver injury, there are currently no data on liver dysfunction in hospitalized COVID‐19 patients in Europe. The aim of this study was to describe the prevalence and predictive value of abnormal liver function in patients hospitalized with COVID‐19. This was a retrospective cohort study of confirmed COVID‐19 patients hospitalized in two referral hospitals in France. Clinical, biological, and radiological data were collected and analyzed. Two hundred and thirty‐four patients confirmed to have COVID‐19 by RT‐PCR were included. Liver function was abnormal in 66.6% of patients on admission. In multivariate logistic regression, abnormal liver test on admission were associated with in‐hospital aggravation (OR=4.1, 95%CI 1.5‐10.8; p=0.004) and mortality (OR 3.3; 95% CI=1.04‐10.5; p=0.04). This study of liver tests in a European COVID‐19 population confirms a high prevalence of abnormal liver tests on admission that are predictive of severe disease course and higher in‐hospital mortality.


Risk of coronavirus infections among medical personnel


title: Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

text: The new porcine epidemic diarrhea (PED) has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV) infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.


title: Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

text: BACKGROUND: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. METHODS: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. FINDINGS: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. INTERPRETATION: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. FUNDING: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.


title: Zoonoses in the Emergence of Human Viral Diseases

text: Viral zoonoses have represented a significant public health problem throughout history, affecting all continents. Furthermore, many viral zoonoses have emerged or reemerged in recent years, highlighting the importance of such diseases. Emerging viral zoonoses encompass a vast number of different viruses and many different transmission modes. There are many factors influencing the epidemiology of the various zoonoses, such as ecological changes, changes in agriculture and food production, the movement of pathogens, including via travel and trade, human behavior and demographical factors, and microbial changes and adaptation. Cost-effective prevention and control of emerging viral zoonoses necessitates an interdisciplinary and holistic approach and international cooperation. Surveillance, laboratory capability, research, training and education, and last but not least, information and communication are key elements.


title: Viral etiology of respiratory infections in children in southwestern Saudi Arabia using multiplex reverse-transcriptase polymerase chain reaction

text: OBJECTIVES: To investigate 15 respiratory viruses in children with acute respiratory tract infections (ARTIs) using multiplex reverse-transcriptase polymerase chain reaction (RT-PCR), and to analyze the clinical and epidemiological features of these viruses. METHODS: In a cross-sectional study, 135 children, ≤5 years of age who presented with ARTIs in Najran Maternity and Children Hospital, Najran, Saudi Arabia between October 2012 and July 2013 were included. The clinical and sociodemographic data, and the laboratory results were recorded using a standardized questionnaire. Two nasopharyngeal swabs were collected from each child: one for bacteriological examination, and the second for viral detection using multiplex RT-PCR. RESULTS: A single viral pathogen was detected in 76 patients, viral coinfections in 9, and mixed viral and bacterial pathogens in 15. Respiratory syncytial virus was isolated in 33 patients, human rhinovirus (hRV) in 22, adenovirus (AdV) in 19, human metapneumovirus in 13, influenza virus in 10, parainfluenza virus in 7, human corona virus (hCoV) in 4, and human bocavirus in one. CONCLUSION: Respiratory syncytial virus, hRV, and AdV were the most frequent viruses, accounting for more than two-thirds of the cases. Other viruses, such as MPV, hCoV NL63, and hCoV OC43, may play a role in pediatric ARTIs. Of significance is the potential use of multiplex RT-PCR to provide epidemiological and virological data for early detection of the emergence of novel respiratory viruses in the era of the Middle East respiratory syndrome coronavirus.


title: Eliminating Visual Acuity and Dilated Fundus Exams Improves Cost Efficiency of Performing OCT-Guided Intravitreal Injections

text: PURPOSE: The clinic efficiency and cost savings achieved by eliminating formal visual acuity (VA) and dilated fundus exams (DFEs) were assessed for established patients receiving OCT-guided intravitreal injections. DESIGN: Comparative cost analysis METHODS: Two different treatment models were evaluated. The first model included patients undergoing routine VA assessment, DFEs, OCT imaging, and intravitreal injections. The second model eliminated the routine VA assessment and DFE, while utilizing OCT imaging through an undilated pupil followed by the intravitreal injection. The two models incorporated both bevacizumab and aflibercept. The number of patients per clinic day, the cost per visit, and the daily revenues were compared between the two models. RESULTS: Optimized schedules with and without VA assessments and DFEs allowed for 48 and 96 patients to be injected per day, respectively. Excluding drug costs, the cost per encounter for the visits with and without a DFE were $39.33 and $22.63, respectively. Including the drug costs, the costs per encounter for the visits with and without a DFE were $85.55 and $68.85 for bevacizumab and $1,787.58 and $1,7770.88 for aflibercept, respectively. Once the reimbursements for each visit type were included, the clinics that eliminated the VA and DFEs were more cost efficient. CONCLUSIONS: Eliminating both VA assessments and DFEs for patients undergoing OCT-guided retreatment with intravitreal injections resulted in decreased exposure times between patients and clinic staff, decreased cost per encounter, and increased patient volumes per clinic day, resulting in improved clinic efficiency and safety while seeing more patients in a clinic day.


title: Risks of ACE Inhibitor and ARB Usage in COVID‐19: Evaluating the Evidence

text: Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID‐19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID‐19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.


title: Indications and Findings on Transthoracic Echocardiogram in COVID-19

text: ABSTRACT Background Despite growing evidence of cardiovascular complications associated with novel 2019 coronavirus disease (COVID-19), there is little data regarding the performance of transthoracic echocardiography (TTE) and spectrum of echocardiographic findings in this disease. Methods We performed a retrospective analysis of adult patients admitted to a quaternary care center in New York City between March 1st and April 3rd, 2020. Patients were included if they had a TTE performed during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. Results Of 749 patients, 72 (9.6%) had a TTE following a positive SARS-CoV-2 PCR test. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). While most patients had preserved biventricular function, 34.7% were found to have a left ventricular ejection fraction (LVEF) ≤ 50% and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation there was an inverse relationship between high sensitivity Troponin T and LVEF (rho = -0.34, p=0.006). Among 20 patients with prior echocardiograms, only two (10%) patients had a new reduction in LVEF of more than 10%. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. Conclusions This study describes the clinical indications for usage and diagnostic performance, as well as findings seen on TTE in hospitalized patients with COVID-19. In appropriately selected patients TTE can be an invaluable tool for guiding COVID-19 clinical management.


Plagues, Public Health, and Politics


title: Prevalence and Seasonal Distribution of Respiratory Viruses During the 2014 - 2015 Season in Istanbul

text: BACKGROUND: Acute respiratory tract infection (ARTI) is one of the most common infections worldwide, causing significant morbidity and mortality. OBJECTIVES: This study was conducted to determine the prevalence and seasonal distribution of respiratory viruses in our region, in children and adults with a pre-diagnosis of ARTI. METHODS: A total of 845 nasopharyngeal swab specimens were analyzed with the RespiFinder Smart 22 kit (PathoFinder BV, Netherlands) and the Rotor-Gene 6000 real-time PCR system. RESULTS: At least one pathogen was detected in 612 (72.4%) of the specimens. Overall, 902 pathogens were detected; 821 (91%) were viruses and 81 (9%) were bacteria. The most commonly detected pathogens were influenza A virus (IFV-A) (n = 219), influenza B virus (IFV-B) (n=157), rhinovirus/enterovirus (n = 107), human bocavirus (HBoV) (n = 91), respiratory syncytial virus (RSV) A/B (n = 64), adenovirus (n = 56), human coronaviruses (n = 51), Mycoplasma pneumoniae (n = 49), parainfluenza viruses (n = 40), human metapneumovirus (n = 36), Bordetella pertussis (n = 15), Legionella pneumophila (n = 11), and Chlamydophila pneumoniae (n = 6), respectively. Among the 215 (25.4%) co-infected cases, IFV-A/HBoV and IFV-A/IFV-B were the most common co-infections. IFV-A was the most prevalent agent in all age groups except for children under 5 years of age, in whom RSV A/B was the most common pathogen. Approximately two thirds of the respiratory viruses were detected in early spring and winter, with peaks in January, March, and April. CONCLUSIONS: With regard to the prevalence and seasonal distribution of respiratory viruses, our epidemiological data for the 2014 - 2015 season in Istanbul showed a predominance of IFV-A infections with a peak activity in early spring. Enhanced surveillance and early detection of respiratory viral pathogens can be useful in the diagnosis, treatment, and prevention of ARTIs, and for guiding the development of appropriate public health strategies.


title: Shedding of Neospora caninum oocysts by dogs fed different tissues from naturally infected cattle

text: Abstract Neospora caninum is one of the most important causes of abortion in dairy cattle worldwide. The distribution of N. caninum in tissues of adult cattle is unknown and the parasite has not been demonstrated histologically in tissues of cows. In the present study the distribution of N. caninum in different tissues of adult cattle was evaluated by bioassays in dogs. Seventeen dogs (2–3 month-old) were fed different tissues of 4 naturally exposed adult cattle (indirect fluorescent antibody test N. caninum titer ≥400): 5 were fed with masseter; 5 with heart, 3 with liver, 4 with brain, and 3 pups were used as non-infected control. Two dogs fed masseter, 2 fed heart, 1 fed liver, and 3 fed brain shed oocysts, and all dogs presented no seroconvertion to N. caninum during the observation period of 4 weeks. The oocysts were confirmed as N. caninum based on the detection of N. caninum-specific DNA by PCR and sequencing. The results indicate that dogs can be infected by N. caninum with different tissues of infected cattle.


Group C Betacoronavirus in Bat Guano Fertilizer, Thailand


title: Bluetongue virus – 23 stimulates inducible nitric oxide synthase expression and nitric oxide production in mononuclear cells of blood and/or regional lymphoid organs

text: Mononuclear leukocytes of peripheral blood mononuclear cells (PBMCs) and regional lymphoid organs (RLOs) play a critical role in primary BTV replication and subsequent viral dissemination to distant systemic organs. The lesions in animals develop primarily as a result of vascular insult, presumably induced by the activity of viral and/or proinflammatory vasoactive mediators. Hence, the current study was designed in sheep to investigate the responses of potent vasoactivators, inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) in mononuclear leukocytes of PBMCs and RLOs. The results show that BTV infection of sheep led to enhanced transcription of iNOS in PBMCs and in particular RLOs. The BTV RNAs and/or antigens were readily demonstrable in these mononuclear leukocytes, suggesting the possible role of BTV in iNOS induction. Moreover, upon in vitro infection of PBMCs with BTV-23, iNOS was up-regulated in time-dependent fashion and correlated with increased NO production. The results from these in vivo and in vitro studies thus suggest iNOS and NO produced by mononuclear leukocytes may potentially contribute to vascular-related pathology of BT.


title: Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation

text: Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating ribosome recruitment. Our data uncovers a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifies the first host factor with pan-norovirus pro-viral activity.


title: The role of electron microscopy in the rapid diagnosis of viral infections — review

text: Electron microscopy (EM) allows fast visualization of viruses in a wide range of clinical specimens. Viruses are grouped into families based on their morphology. Viruses from various families look distinctly and these morphological variances are the basis for identification of viruses by EM. The identification to the family level is often sufficient for the clinician or recognition of an unknown infectious agent. Diagnostic EM has two advantages over enzyme-linked immunosorbent assay and nucleic acid amplification tests. After a simple and fast negative staining, EM allows fast morphological identification and differential diagnosis of infectious agents contained in the specimen without the need for special considerations and/or reagents. Nevertheless, EM has the disadvantage of being unsuitable as a screening method.


title: Aligning the “Manifesto for a European Research Network into Problematic Usage of the Internet” with the Diverse Needs of the Professional and Consumer Communities Affected by Problematic Usage of Pornography

text: The Manifesto for a European research network into Problematic Usage of the Internet was published in May 2018. It was written from the perspective of the COST Action Network, a programme of the European Cooperation in Science and Technology CA16207 and is expected to have significant influence on research funding priorities over the next decade. The Manifesto identified nine key research priorities to advance understanding in the field. Our analysis shows that while at the most general level it identified problematic usage of pornography (PUP) as a key research priority, it then barely mentioned it again within the body of the report. This paper uses the Manifesto’s framework to suggest research areas into the problematic usage of pornography which are of particular relevance to clinicians and other professionals working in the field who want to develop approaches to assist individuals and target groups affected by PUP. It also looks at potential research opportunities inspired by the lived-experience of users withdrawing from PUP. A large number of opportunities are identified for new work on PUP across all nine key research areas of the Manifesto.


title: Two outbreaks of SARS-CoV-2 in department of surgery in a Wuhan hospital

text: Summary The outbreak of SARS-CoV-2 in China, attracted a large number of medical staff to help in the city's hospitals and this put them at a high risk of infection. We describe twenty medical staff who were diagnosed with COVID-19 within one week in the department of surgery in a Wuhan hospital. Epidemiological investigation of these cases identified misdiagnosed patients (source of infection), an inappropriate clinical meeting and working without wearing face masks to be the causes of the outbreaks. This report emphasizes the importance of wearing a facemask and applying other standard infection control precautions to protect medical personnel from infection with the virus.


title: Vector competence of anthropophilic mosquitoes for a new mesonivirus in Senegal

text: The mesoniviruses (MESOVs) belong to the newly described Mesoniviridae family (Order: Nidovirales). They have never been reported in Senegal until recently during a study in arbovirus emergence with the detection of a new species of MESOV named Dianke virus (DKV) from common mosquitoes from eastern Senegal. Actually, their vector competence for this newly described DKV is unknown. We, therefore, estimated the vector competence of Culex tritaeniorhynchus, Culex quinquefasciatus, Aedes aegypti, and Anopheles gambiae mosquitoes collected in Senegal for DKV using oral infection. Whole bodies, legs/wings, and saliva samples were tested for DKV by RT–PCR to estimate infection, dissemination, and transmission rates. The infectivity of virus particles in the saliva was confirmed by infecting C6/36 cells. Virus transmission rates were up to 95.45% in Culex tritaeniorhynchus, 28% in Cx. quinquefasciatus and 9.09% in Aedes aegypti. Viral particles in the saliva were confirmed infectious by C6/36 cell culture. An. gambiae was able to disseminate DKV only at 20 days post-infection. This study shows that Culex mosquitoes are more competent than Ae. aegypti for DKV, while Anopheles gambiae is not likely a competent vector.


title: The care of patients with Duchenne, Becker, and other muscular dystrophies in the COVID‐19 pandemic

text: The coronavirus disease 2019 (COVID‐19) pandemic has resulted in the reorganization of health‐care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID‐19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic. We address issues surrounding corticosteroid and exon‐skipping treatments, cardiac medications, hydroxychloroquine use, emergency/respiratory care, rehabilitation management, and the conduct of clinical trials. We highlight the importance of collaborative treatment decisions between the patient, family, and health‐care provider, considering any geographic or institution‐specific policies and precautions for COVID‐19. We advocate for continuing multidisciplinary care for these patients using telehealth.


Coinfections in Hospitalized Children With Community-Acquired Pneumonia: What Does This Mean for the Clinician?


title: V Repiratory Tract

text: Publisher Summary This chapter discusses respiratory tract. This chapter illustrates that a complex array of defensive mechanisms protect the lungs against the adverse effects of airborne substances and pathogenic organisms. In contrast to the adverse pulmonary effects of cigarette smoke and industrial pollutants, therapeutic agents remain a relatively minor cause of pulmonary toxicity in man although, actual incidence is difficult to ascertain. However, drug-induced pulmonary disease appears to be an increasingly frequent clinical problem and the drugs associated with parenchymal pulmonary injury in humans continue to increase. The development of drugs to be administered by inhalation or intranasal routes is particularly difficult because of the perceived risks of high local drug concentration in respiratory tissues, alterations to drug disposition and a potentially vulnerable patient population, often with pulmonary disease. Finally, the nasal chambers are the structures, which are first to be subjected to the effects of inhaled substances, whether microorganisms or chemical substances. Moreover, infectious agents cause inflammation in the nose and nasal sinuses, and this may be associated with inflammation in the conjunctiva, middle ear and oral cavity.


title: Covid‐19 and neurodegeneration. What can we learn from the past?

text: Coronaviridae (CoVs) are single stranded RNA viruses. βeta‐CoVs encompasses Bat coronavirus (BCoV), the human Severe Acute Respiratory Syndrome (SARS) virus and the Middle Eastern Respiratory Syndrome (MERS) virus. In December 2019, a new βeta‐CoVs was identified in Wuhan, China, SARS‐CoV‐2. The genome sequencing demonstrated a 79.5% and 96.2% identity to SARS‐CoV and a bat CoV genome, respectively, supporting the interspecies transmission and the origin of this new pandemia.


docid: lobhurai

title: Vitamin D(3) and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial

text: BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D(3) supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. METHODS: We randomized 600 students into 4 treatment arms: 1) vitamin D(3) and gargling, 2) placebo and gargling, 3) vitamin D(3) and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D(3) reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI(95):0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI(95):0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D(3) treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI(95):0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log(10) viral copies/mL (mean difference: -0.89, CI(95:) -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI(95):0.53-1.26, p = 0.36). CONCLUSIONS: These results suggest that vitamin D(3) is a promising intervention for the prevention of URTI. Vitamin D(3) significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. TRIAL REGISTRATION: Clinical Trials Registration: NCT01158560.


title: COVID-19 Worries and Behavior Changes in Older and Younger Men and Women

text: OBJECTIVES: The case fatality rate of coronavirus disease 2019 (COVID-19) is higher among older adults than younger adults and is also higher among men than women. However, worry, which is a key motivator of behavioral health changes, occurs less frequently for older than younger adults, and less frequently for men than women. Building on this, we tested whether older adults–and particularly older men—would report the least amount of COVID-19 worry and also fewer COVID-19 behavior changes. METHOD: From March 23–31, 2020, we administered an online questionnaire assessing COVID-19 perceptions, worries, and behavior changes. Participants were a convenience sample of U.S. residents, who were community-dwelling younger adults (18–35) or older adults (65–81). Analyses included 146 younger adults (68 men, 78 women) and 156 older adults (82 men, 74 women). Participants were predominately white, living in suburban/urban areas, and had completed some college. RESULTS: During the early phase of the outbreak in the United States, older adults perceived the risks of COVID-19 to be higher than did younger adults. Despite this, older men were comparatively less worried about COVID-19 than their younger counterparts. Compared with the other participants, older men had also implemented the fewest behavior changes. DISCUSSION: Interventions are needed to increase COVID-19 behavior changes in older men. These results also highlight the importance of understanding emotional responses to COVID-19, as these are predictive of their behavioral responses.


title: Algal Lectins as Potential HIV Microbicide Candidates

text: The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are endowed with potent anti-HIV activity. In fact, a number of algal lectins such as cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria agardhii agglutinin and griffithsin are considered as potential microbicide candidates to prevent the sexual transmission of HIV through topical applications. They not only inhibit infection of cells by cell-free virus but they can also efficiently prevent virus transmission from virus-infected cells to uninfected CD4(+) target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and transmission to CD4(+) T lymphocytes. This review focuses on the structural properties and carbohydrate specificity of these algal lectins, their antiviral activity against HIV and several other enveloped viruses, their safety profile and viral resistance patterns.


docid: vtgdqart

title: Effect of Pullet Vaccination on Development and Longevity of Immunity

text: Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent.


title: T-01: Taux élevé d’infections respiratoires virales chez les patients hospitalisés et le personnel soignant, hiver 2014

text: Introduction – objectifs Déterminer la prévalence des infections respiratoires virales symptomatiques ou non parmi les patients et les soignants d’un service de maladies infectieuses. Rechercher les facteurs associés à la transmission nosocomiale. Matériels et méthodes Les patients hospitalisés entre le 15/01 (S1) et le 30/03/14 (S10) sont inclus prospectivement, avec recueil de données cliniques, prélèvement nasopharyngé tous les 2 à 5 jours pour PCR multiplex à la recherche de 22 pathogènes. Les soignants ont un prélèvement à S5 et en cas de symptôme. Une sérologie est faite chez les patients symptomatiques et le personnel, avec contrôle à S4. Résultats Après 7 semaines sur 10 de l’étude toujours en cours, il y a eu 35 infections respiratoires chez 44 % (28/64) du personnel. Un virus était présent dans 25 des 35 prélèvements (71 %) : 12 coronavirus (48 % : 7 OC43, 3 NL63, 2 HKU1), 6 PIV4 (24 %), 5 influenza A (20 %, dont 3 H1N1pdm09), 5 rhinovirus (20 %) et 1 VRS. Dans 4 prélèvements (11 %) plus d’un virus était identifié. Sur 105 patients inclus, 45 avaient des signes d’infection respiratoire (44 %), parmi lesquels 27 prélèvements étaient positifs (60 %) pour 34 virus : 5 coronavirus (12 % : 2 OC43, 2 NL63, 1 229E), 2 PIV (1 PIV1 et 1 PIV2), 16 influenza A (47 %, dont 8 H1N1pdm09), 10 rhinovirus (29 %) et 1 hMPV. Dans 7 prélèvements (26 %) plus d’un virus était identifié. Les taux de vaccination anti-grippale étaient de 70 % (45/64) chez les soignants (mais 42 %, 8/19, chez les étudiants hospitaliers). Quelques cas de potentielle transmission dans le service sur des critères chronologiques et virologiques ont été identifiés. Conclusion Les infections virales respiratoires sont fréquentes chez les soignants en période hivernale, avec un risque de transmission aux patients et aux autres soignants.


title: Clinical Implications of Chloroquine and Hydroxychloroquine Ototoxicity for COVID-19 Treatment: A Mini-Review

text: At this time of the COVID-19 pandemic, potentially effective treatments are currently under urgent investigation. Benefits of chloroquine and hydroxychloroquine for the treatment of COVID-19 infection have been proposed and clinical trials are underway. Chloroquine and hydroxychloroquine, typically used for the treatment of malaria and autoimmune diseases, have been considered for off-label use in several countries. In the literature, there are reports of ototoxic effects of the drugs causing damage to the inner ear structures, which then result in hearing loss, tinnitus, and/or imbalance. This mini-review represents a summary of the findings from a systematic search regarding ototoxicity of chloroquine and hydroxychloroquine in the published literature. The characteristics of sensorineural hearing loss and/or tinnitus after chloroquine or hydroxychloroquine treatment can be temporary but reports of persistent auditory and vestibular dysfunction exist. These are not frequent, but the impact can be substantial. Additionally, abnormal cochleovestibular development in the newborn was also reported after chloroquine treatment in pregnant women. The suggested dose of chloroquine for COVID-19 infection is considerably higher than the usual dosage for malaria treatment; therefore, it is plausible that the ototoxic effects will be greater. There are potential implications from this review for survivors of COVID-19 treated with chloroquine or hydroxychloroquine. Patient reports of hearing loss, tinnitus, or imbalance should be noted. Those with troublesome hearing loss, tinnitus and/or imbalance are encouraged to be referred for hearing evaluation and interventions once they are stable. Clinical trials of chloroquine or hydroxychloroquine should also consider including audiological monitoring in the protocol.


title: The Emergence of Ebola as a Global Health Security Threat: From ‘Lessons Learned’ to Coordinated Multilateral Containment Efforts

text: First reported in remote villages of Africa in the 1970s, the Ebolavirus was originally believed to be transmitted to people from wild animals. Ebolavirus (EBOV) causes a severe, frequently fatal hemorrhagic syndrome in humans. Each outbreak of the Ebolavirus over the last three decades has perpetuated fear and economic turmoil among the local and regional populations in Africa. Until now it has been considered a tragic malady confined largely to the isolated regions of the African continent, but it is no longer so. The frequency of outbreaks has increased since the 1970s. The 2014 Ebola outbreak in Western Africa has been the most severe in history and was declared a public health emergency by the World Health Organization. Given the widespread use of modern transportation and global travel, the EBOV is now a risk to the entire Global Village, with intercontinental transmission only an airplane flight away. Clinically, symptoms typically appear after an incubation period of approximately 11 days. A flu-like syndrome can progress to full hemorrhagic fever with multiorgan failure, and frequently, death. Diagnosis is confirmed by detection of viral antigens or Ribonucleic acid (RNA) in the blood or other body fluids. Although historically the mortality of this infection exceeded 80%, modern medicine and public health measures have been able to lower this figure and reduce the impact of EBOV on individuals and communities. The treatment involves early, aggressive supportive care with rehydration. Core interventions, including contact tracing, preventive initiatives, active surveillance, effective isolation and quarantine procedures, and timely response to patients, are essential for a successful outbreak control. These measures, combined with public health education, point-of-care diagnostics, promising new vaccine and pharmaceutical efforts, and coordinated efforts of the international community, give new hope to the Global effort to eliminate Ebola as a public health threat. Here we present a review of EBOV infection in an effort to further educate medical and political communities on what the Ebolavirus disease entails, and what efforts are recommended to treat, isolate, and eventually eliminate it.


Serosurveys and convalescent plasma in COVID-19


title: Factors Affecting the Effectiveness of Hospital Incident Command System; Findings from a Systematic Review

text: OBJECTIVE: To examine all aspects affecting the functioning of the system and the most important factors in its assessment through a systematic review during 1990 to 2017. METHODS: This systematic review of the current literature study was conducted during July 2017, and all articles, books, guidelines, manuals and dissertations pertaining to the Incident Command System were analyzed. A total of articles and relevant documents were identified and finally these articles, which we found, were analyzed based on the specified indicators. RESULTS: In this research 992 articles and relevant documents were identified and eventually, 48 articles were included and analyzed. The results were categorized into 6 main groups including 65 subgroups and 221 variables: features of hospital incident command system (14 subgroups and 53 variables), strengths of the system (15 subgroups and 70 variables), weaknesses of the system (10 subgroups and 15 variables), factors influencing the system's performance improvement (12 subgroups and 42 variables), factors that reduce the effectiveness of system include 11 subgroups (10 internal factors and 1 external factor) and 22 variables and important factors in assessing system performance (2 sub-groups and 19 variables). CONCLUSION: According to the results, Evaluating the effectiveness of a hospital accident command system (HICS) in a valid method can improve the efficiency of this system. In this appraisal, hospital managers and health decision-makers should consider principles, characteristics, strengths and weakness of it.


docid: hbnoeugb

title: Multivesicular Bodies (MVB) Mimicking SARS-CoV-2 in patients without COVID-19


title: Mouse hepatitis virus strain — Related patterns of tissue tropism in suckling mice

text: The pattern of tissue tropism for several prototype and uncharacterized strains of mouse hepatitis virus (MHV) was studied by intranasal inoculation of each virus strain into groups of neonatal Swiss mice under otherwise identical conditions. Mice were killed at intervals up to 18 days after inoculation, and their tissues were examined for the presence of MHV antigen by indirect immunofluorescence. Two patterns of infection were apparent. Prototype MHV strains 1, 3, A59, JHM, S and uncharacterized MHV strains Tettnang and wt-1 produced a respiratory pattern, in which nose and lung were consistently involved with dissemination to other organs in a vascular distribution. Pulmonary vascular endothelium and alveolar septal cells, but not airway epithelium, were infected. An enteric pattern was observed with MHV-Y and wt-2 in which MHV antigen was largely restricted to the nose and bowel, with limited dissemination to other abdominal organs but not lung. Intestinal lesions in these mice were severe compared to those manifesting the respiratory pattern of infection. These results indicate that, like coronaviruses of other species, different strains of MHV possess different primary and secondary organotropisms following a natural route of inoculation in a susceptible host.


title: Viral and bacterial etiology of severe acute respiratory illness among children < 5 years of age without influenza in Niger

text: BACKGROUND: Globally, pneumonia is the leading cause of morbidity and mortality in children, with the highest burden experienced in sub-Saharan Africa and Asia. However, there is a dearth of information on the etiology of severe acute respiratory illness (SARI) in Africa, including Niger. METHODS: We implemented a retrospective study as part of national influenza sentinel surveillance in Niger. We randomly selected a sample of nasopharyngeal specimens collected from children <5 years of age hospitalized with SARI from January 2010 through December 2012 in Niger. The samples were selected from individuals that tested negative by real-time reverse transcription polymerase chain reaction (rRT-PCR) for influenza A and B virus. The samples were analyzed using the Fast Track Diagnostic Respiratory Pathogens 21plus Kit (BioMérieux, Luxemburg), which detects 23 respiratory pathogens including 18 viral and 5 bacterial agents. RESULTS: Among the 160 samples tested, 138 (86 %) tested positive for at least one viral or bacterial pathogen; in 22 (16 %) sample, only one pathogen was detected. We detected at least one respiratory virus in 126 (78 %) samples and at least one bacterium in 102 (64 %) samples. Respiratory syncytial virus (56/160; 35 %), rhinovirus (47/160; 29 %) and parainfluenza virus (39/160; 24 %) were the most common viral pathogens detected. Among bacterial pathogens, Streptococcus pneumoniae (90/160; 56 %) and Haemophilus influenzae type b (20/160; 12 %) predominated. CONCLUSIONS: The high prevalence of certain viral and bacterial pathogens among children <5 years of age with SARI highlights the need for continued and expanded surveillance in Niger.


title: Newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV), a member of the Coronaviridae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome (ARDS), as well as extrapulmonary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here, we generated recombinant nonvirulent Newcastle disease virus (NDV) LaSota strain expressing MERS-CoV S protein (designated as rLa-MERS-S), and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa-MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.


title: Redefining Pathways into Acute Rehabilitation during the COVID‐19 Crisis

text: The coronavirus disease 2019 (COVID‐19) pandemic has necessitated drastic changes across the spectrum of health care, all of which have occurred with unprecedented rapidity. The need to accommodate change on such a large scale has required ingenuity and decisive thinking. The field of physical medicine and rehabilitation has been faced with many of these challenges. Healthcare practitioners in New York City, the epicenter of the pandemic in the United States, were among the first to encounter many of these challenges. One of the largest lessons included learning how to streamline admissions and transfer process into an acute rehabilitation hospital as part of a concerted effort to make acute care hospital beds available as quickly as possible.


title: Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19

text: Abstract Background A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), outbroke in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stays, progression and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. Methods 83 confirmed COVID-19 patients were divided into the CVD (n=42) and non-CVD (n=41) group according to their medical history. Medical records information including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT) as well as treatment measures were collected, analyzed and compared between two groups. Results COVID-19 patients with CVD showed: (1) more severe pathological changes in the lung, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK) and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. Conclusions Our data indicated that CVD is a strong risk factor for a rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.


title: Plans to Reactivate Gastroenterology Practices Following the COVID-19 Pandemic: A Survey of North American Centers

text: Abstract: Background and Aims Practices dramatically reduced endoscopy services due to the COVID-19 pandemic. As practices are now considering reintroduction of elective endoscopy, we conducted a survey of North American practices to identify reactivation barriers and strategies. Methods We designed and electronically distributed a web-based survey to North American gastroenterologists consisting of seven domains: institutional demographics, impact of COVID-19 on endoscopy practice, elective endoscopy resumption plans, anesthesia modifications, personal protective equipment (PPE) policies, fellowship training and telemedicine use. Responses were stratified by practice type: ambulatory surgery center (ASC) or hospital-based. Results In total, 123 practices (55% ASC-based and 45% hospital-based) responded. At the pandemic’s peak (as reported by the respondent), practices saw a 90% drop in endoscopy volume with most centers planning to resume elective endoscopy a median of 55 days after initial restrictions. Declining community prevalence of COVID-19, PPE availability, and pre-procedure SARS-CoV-2 testing availability were ranked as the three primary factors influencing reactivation timing. ASC-based practices were more likely to identify pre-procedure testing availability as a major factor limiting elective endoscopy resumption (p=0.001). Pre-procedure SARS-CoV-2 testing was planned by only 49.2% of practices overall; when testing is performed and negative, 52.9% of practices will continue to utilize N95 masks. Conclusion This survey highlights barriers and variable strategies for reactivation of elective endoscopy services following the COVID-19 pandemic. Our results suggest that more widespread access to pre-procedure SARS-CoV-2 tests with superior performance characteristics is needed to increase provider and patient comfort in proceeding with elective endoscopy.


Decisions in HCT and wine-making


title: A Downward Trend of the Ratio of Influenza RNA Copy Number to Infectious Viral Titer in Hospitalized Influenza A-Infected Patients

text: Background. Efficacy endpoints in influenza clinical trials may include clinical symptoms and virological measurements, although virology cannot serve as the primary endpoint. We investigated the relationship between influenza A RNA copy number and quantity of infectious viruses in hospitalized influenza patients. Methods. One hundred fifty influenza-infected, hospitalized patients were included in this prospective cohort study spanning the 2012–2013 influenza season. Daily nasopharyngeal samples were collected during hospitalization, and influenza A RNA copy number and infectious viral titer were monitored. Results. The decay rate for 50% tissue culture infectious dose (TCID(50)) was 0.51 ± 0.14 log(10) TCID(50)/mL per day, whereas the RNA copy number decreased at a rate of 0.41 ± 0.04 log(10) copies/mL per day (n = 433). The log ratio of the RNA copy number to the infectious viral titer within patient changes significantly with −0.25 ± 0.09 units per day (P = .0069). For a 12-day observation period, the decay corresponds to a decline of this ratio of 3 log influenza RNA copies. Conclusions. Influenza RNA copy number in nasal swabs is co-linear with culture, although the rate of decay of cell culture-based viral titers was faster than that observed with molecular methods. The study documented a clear decreasing log ratio of the RNA copy number to the infectious viral titer of the patients over time.


title: Applicability of time fractional derivative models for simulating the dynamics and mitigation scenarios of COVID-19

text: Fractional calculus provides a promising tool for modeling fractional dynamics in computational biology, and this study tests the applicability of fractional-derivative equations (FDEs) for modeling the dynamics and mitigation scenarios of the novel coronavirus for the first time. The coronavirus disease 2019 (COVID-19) pandemic radically impacts our lives, while the evolution dynamics of COVID-19 remain obscure. A time-dependent Susceptible, Exposed, Infectious, and Recovered (SEIR) model was proposed and applied to fit and then predict the time series of COVID-19 evolution observed over the last three months (up to 3/22/2020) in China. The model results revealed that 1) the transmission, infection and recovery dynamics follow the integral-order SEIR model with significant spatiotemporal variations in the recovery rate, likely due to the continuous improvement of screening techniques and public hospital systems, as well as full city lockdowns in China, and 2) the evolution of number of deaths follows the time FDE, likely due to the time memory in the death toll. The validated SEIR model was then applied to predict COVID-19 evolution in the United States, Italy, Japan, and South Korea. In addition, a time FDE model based on the random walk particle tracking scheme, analogous to a mixing-limited bimolecular reaction model, was developed to evaluate non-pharmaceutical strategies to mitigate COVID-19 spread. Preliminary tests using the FDE model showed that self-quarantine may not be as efficient as strict social distancing in slowing COVID-19 spread. Therefore, caution is needed when applying FDEs to model the coronavirus outbreak, since specific COVID-19 kinetics may not exhibit nonlocal behavior. Particularly, the spread of COVID-19 may be affected by the rapid improvement of health care systems which may remove the memory impact in COVID-19 dynamics (resulting in a short-tailed recovery curve), while the death toll and mitigation of COVID-19 can be captured by the time FDEs due to the nonlocal, memory impact in fatality and human activities.


docid: uwchiawn

title: Elektronenmikroskopischer Direktnachweis von Viruspartikeln bei Gastroenteritis im Säuglings- und Kleinkindesalter

text: In 72 faecal extracts examined from babies and infants with an acute gastroenteritis, virus particles were found in 29 cases. These particles could be classified as reovirus-like in 16 cases, coronaviruses in 11 cases and adenoviruses in 2 cases. The electron microscopic investigation of 11 faecal extracts from healthy babies did not show any of these particles. Comparative studies on the concentration methods were performed.


title: Human rhinovirus infection in young African children with acute wheezing

text: BACKGROUND: Infections caused by human rhinoviruses (HRVs) are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. METHODS: Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. RESULTS: HRV was detected in 128 (58.2%) of children, most (72%) of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35%) were hospitalized for treatment and 3 (2%) were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52%) followed by HRV-A (37%) and HRV-B (11%). Infection with other respiratory viruses occurred in 20/128 (16%) of HRV-positive children and in 26/92 (28%) of HRV-negative samples. CONCLUSION: HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.


title: Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures

text: BACKGROUND: Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model. METHODS: Well-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air–liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays. RESULTS: H7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed. CONCLUSIONS: Both rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.


title: Long-term Institutional Experience with Telemedicine Services for Radiation Oncology: A Potential Model for Long-term Utilization

text: Abstract With the development of the COVID-19 pandemic, healthcare practices and radiation oncology departments have begun to incorporate telemedicine services to practice social distancing and minimize the chances of disease spread. Given the severity of this pandemic, it will likely fundamentally impact the use of these services for years to come. Our institution and radiation oncology department have used telemedicine services for many years; we would like to report on our departmental experience to guide other radiation oncology practices on its long-term use for clinical evaluation and patient care. Our institution’s telemedicine program provides clinical services for a number of remote locations and represents the largest telehealth network in the world, with over 300 sites and 60,000 patient encounters a year. Specifically for our radiation oncology department, over 200 patient encounters occur via telemedicine a year. Patients report great appreciation and satisfaction with these encounters, as they eliminate the time and energy needed for travel from long distances. It has resulted in improved efficiency and cost-effectiveness as well. Based on our institutional experience, our long-term vision for telemedicine (after the COVID-19 pandemic has hopefully subsided) is as an excellent and cost-efficient tool to provide long-term follow-up for patients, especially for those who live far away in rural or underserved areas.


title: Genomic and proteomic approaches for studying human cancer: Prospects for true patient-tailored therapy

text: Global gene expression analysis is beginning to move from the laboratories of basic investigators to large-scale clinical trials. The potential of this technology to improve diagnosis and tailored treatment of human disease may soon be realised, now that several comprehensive studies have demonstrated the utility of gene expression profiles for the classification of tumours into distinct, clinically relevant subtypes and the prediction of clinical outcomes. In addition, new data from the emerging proteomics platforms add another layer of molecular information to the study of human disease, as scientists attempt to catalogue a complete inventory of the proteins encoded by the genome and to establish a 'biosignature' profile of human health and disease. As a result, it is anticipated that, together, these technologies will facilitate the comprehensive study of genes, gene products and signalling pathways so that the objective of personalised molecular medicine can be achieved. This paper will review the studies that best demonstrate how genomics and proteomics technologies can be used to improve cancer diagnosis and treatment it will specifically highlight the important work being incorporated into clinical trials.


docid: vpqzjkhn

title: Polymorphisms in the S1 spike glycoprotein of Arkansas-type infectious bronchitis virus (IBV) show differential binding to host tissues and altered antigenicity

text: Abstract Sequencing avian infectious bronchitis virus spike genes re-isolated from vaccinated chicks revealed that many sequence changes are found on the S1 spike gene. In the ArkDPI strain, Y43H and ∆344 are the two most common changes observed. This study aims to examine the roles of Y43H and ∆344 in selection in vivo. Using recombinant ArkDPI S1 proteins, we conducted binding assays on chicken tracheas and embryonic chorioallantoic membrane (CAM). Protein histochemistry showed that the Y43H change allows for enhanced binding to trachea, whereas the ArkDPI S1 spike with H43 alone was able to bind CAM. Using Western blot under denaturing conditions, ArkDPI serotype-specific sera did not bind to S1 proteins with ∆344, suggesting that ∆344 alters antigenicity of S1. These findings are important because they propose that specific changes in S1 enhances virus fitness by more effective binding to host tissues (Y43H) and by evading a vaccine-induced antibody response (∆344).


title: Spatial approximations of network-based individual level infectious disease models

text: Abstract Often, when modeling infectious disease spread, the complex network through which the disease propagates is approximated by simplified spatial information. Here, we simulate epidemic spread through various contact networks and fit spatial-based models in a Bayesian framework using Markov chain Monte Carlo methods. These spatial models are individual-level models which account for the spatio-temporal dynamics of infectious disease. The focus here is on choosing a spatial model which best predicts the true probabilities of infection, as well as determining under which conditions such spatial models fail. Spatial models tend to predict infection probability reasonably well when disease spread is propagated through contact networks in which contacts are only within a certain distance of each other. If contacts exist over long distances, the spatial models tend to perform worse when compared to the network model.


title: Endoplasmic reticulum: a focal point of Zika virus infection

text: Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family. It is an arbovirus that can cause congenital abnormalities and is sexually transmissible. A series of outbreaks accompanied by unexpected severe clinical complications have captured medical attention to further characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. Endoplasmic reticulum (ER) and ER-related proteins are essential in ZIKV genome replication. This review highlights the subcellular localization of ZIKV to the ER and ZIKV modulation on the architecture of the ER. This review also discusses ZIKV interaction with ER proteins such as signal peptidase complex subunit 1 (SPCS1), ER membrane complex (EMC) subunits, and ER translocon for viral replication. Furthermore, the review covers several important resulting effects of ZIKV infection to the ER and cellular processes including ER stress, reticulophagy, and paraptosis-like death. Pharmacological targeting of ZIKV-affected ER-resident proteins and ER-associated components demonstrate promising signs of combating ZIKV infection and rescuing host organisms from severe neurologic sequelae.


title: Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions

text: Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics.


title: Severe COVID-19: A Review of Recent Progress With a Look Toward the Future

text: The novel coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the World Health Organization has confirmed that COVID-19 is a global infectious disease pandemic. This is the third acute infectious disease caused by coronavirus infection in this century, after sudden acute respirator syndrome and Middle East respiratory syndrome. The damage mechanism of SARS-CoV-2 is still unclear. It is possible that protein S binds to angiotensin-converting enzyme 2 receptors and invades alveolar epithelial cells, causing direct toxic effects and an excessive immune response. This stimulates a systemic inflammatory response, thus forming a cytokine storm, which leads to lung tissue injury. In severe cases, the disease can lead to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Patients with severe COVID-19 have a relatively high mortality rate. Currently, there are no specific antiviral drugs for the treatment of COVID-19. Most patients need to be admitted to the intensive care unit for intensive monitoring and supportive organ function treatments. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment methods of severe COVID-19 and puts forward some tentative ideas, aiming to provide some guidance for the diagnosis and treatment of severe COVID-19.


title: Prospective Evaluation for Respiratory Pathogens in Children With Sickle Cell Disease and Acute Respiratory Illness

text: BACKGROUND: Human rhinovirus (HRV), human coronavirus (hCoV), human bocavirus (hBoV), and human metapneumovirus (hMPV) infections in children with sickle cell disease have not been well studied. PROCEDURE: Nasopharyngeal wash specimens were prospectively collected from 60 children with sickle cell disease and acute respiratory illness, over a 1-year period. Samples were tested with multiplexed-PCR, using an automated system for nine respiratory viruses, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Clinical characteristics and distribution of respiratory viruses in patients with and without acute chest syndrome (ACS) were evaluated. RESULTS: A respiratory virus was detected in 47 (78%) patients. Nine (15%) patients had ACS; a respiratory virus was detected in all of them. The demographic characteristics of patients with and without ACS were similar. HRV was the most common virus, detected in 29 of 47 (62%) patients. Logistic regression showed no association between ACS and detection of HRV, hCoV, hBoV, hMPV, and other respiratory pathogens. Co-infection with at least one additional respiratory virus was seen in 14 (30%) infected patients, and was not significantly higher in patients with ACS (P=0.10). Co-infections with more than two respiratory viruses were seen in seven patients, all in patients without ACS. Bacterial pathogens were not detected. CONCLUSION: HRV was the most common virus detected in children with sickle cell disease and acute respiratory illness, and was not associated with increased morbidity. Larger prospective studies with asymptomatic controls are needed to study the association of these emerging respiratory viruses with ACS in children with sickle cell disease.


title: Chapter 26 Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes

text: Abstract The infraclass Palaeognathae includes the flightless ratites (ostrich, emu, rhea, cassowary, kiwi) and the tinamous, a group of related, flighted birds. This chapter focuses on unique anatomy and important non-infectious and infectious diseases of these groups of birds. Notable among these are management-related diseases such as gastrointestinal tract impactions, OIE reportable viral diseases including those cause by the avian influenza and eastern equine encephalitis viruses, and a range of species-specific endo- and ectoparasites virus infections.


docid: qaeygzns

title: Coinfection with SARS‐CoV‐2 and other respiratory pathogens in COVID‐19 patients in Guangzhou, China

text: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; previously provisionally named 2019 novel coronavirus or 2019‐nCoV) disease (COVID‐19) in China at the end of 2019 has caused a global pandemic and remains as a major public health issue This article is protected by copyright. All rights reserved.


title: Impacts of epidemic outbreaks on supply chains: mapping a research agenda amid the COVID-19 pandemic through a structured literature review

text: The coronavirus (COVID-19) outbreak shows that pandemics and epidemics can seriously wreak havoc on supply chains (SC) around the globe. Humanitarian logistics literature has extensively studied epidemic impacts; however, there exists a research gap in understanding of pandemic impacts in commercial SCs. To progress in this direction, we present a systematic analysis of the impacts of epidemic outbreaks on SCs guided by a structured literature review that collated a unique set of publications. The literature review findings suggest that influenza was the most visible epidemic outbreak reported, and that optimization of resource allocation and distribution emerged as the most popular topic. The streamlining of the literature helps us to reveal several new research tensions and novel categorizations/classifications. Most centrally, we propose a framework for operations and supply chain management at the times of COVID-19 pandemic spanning six perspectives, i.e., adaptation, digitalization, preparedness, recovery, ripple effect, and sustainability. Utilizing the outcomes of our analysis, we tease out a series of open research questions that would not be observed otherwise. Our study also emphasizes the need and offers directions to advance the literature on the impacts of the epidemic outbreaks on SCs framing a research agenda for scholars and practitioners working on this emerging research stream.


title: Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong

text: BACKGROUND: Enterovirus 71 (EV71) is a common etiological agent of hand, foot and mouth disease (HFMD) in children. EV71 epidemics have been reported in Hong Kong in recent years, and yet the genetic information of EV71 strains circulating in our locality is limited. The objective of this study was to investigate the genetic evolution of these EV71 isolates in Hong Kong over a 7-year period. METHODS: Twenty-two EV71 isolates from Hong Kong during 2004–2010 were included for phylogenetic analysis using partial VP2-VP3, 2C and 3D regions. Eight EV71 strains were selected for complete genome sequencing and recombination analysis. RESULTS: Among the 22 EV71 isolates, 20 belonged to subgenotype C4 and 2 belonged to subgenotype C2 based on the phylogenetic analysis of partial VP2-VP3, 2C and 3D gene regions. Phylogenetic, similarity plot and bootscan analyses using complete genome sequences of seven EV71 isolates of subgenotype C4 supported that the “double-recombinant” strains of subgenotype C4 persistently circulating in Hong Kong should belong to a newly proposed genotype D. Further analysis revealed two clusters, subgenotypes C4b and C4a (proposed genotypes D1a and D1b respectively), with “genotype D1b” strains being predominant in recent years in Hong Kong. A distinct lineage of EV71 subgenotype C2 has emerged in Hong Kong in 2008. The evolutionary rate of EV71 was 3.1 × 10(-3) nucleotide substitutions per site per year similar to that of other enterovirus, such as EV68, but was relatively lower than those of echovirus 30 and poliovirus. Molecular clock analysis using VP1 gene dated the time to the most recent common ancestor of all EV71 genotypes to 1900s, while the EV71 “double-recombinant” strains of “genotype D” were detected as early as 1998. CONCLUSIONS: This study provides the molecular basis for proposing a new “genotype D” of EV71 and assigning a discrete lineage of subgenotype C2. EV71 strains of “genotype D” have been circulating in Hong Kong for over 7 years, with “genotype D1b” being predominant.


title: Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia

text: The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.


title: Contribution of traditional Chinese medicine to the treatment of COVID-19

text: COVID-19 as an epidemic disease has spread across the planet since December 2019. The somber situation reminds each country to take actions in preventing the spreading of the virus. China as one of the early affected countries has been fighting against the novel coronavirus with the achievements of nearly 80,000 cured confirmed patients. Traditional Chinese medicine (TCM) has made contributions to the treatment of COVID-19 because of its efficacy and comprehensive therapeutic theory. In this commentary, the advantage, aetiology and mechanism of TCM therapy were discussed in the aspect of its functions in reducing the harms brought by COVID-19 to human beings.


title: Broad reception for coronavirus

text: The discovery that a new coronavirus associated with lethal respiratory infections binds to an evolutionarily conserved receptor on airway cells suggests that direct transmission from bats to humans may occur. See Letter p.251


title: Generation of Complete Multi−Cell Type Lung Organoids From Human Embryonic and Patient‐Specific Induced Pluripotent Stem Cells for Infectious Disease Modeling and Therapeutics Validation

text: The normal development of the pulmonary system is critical to transitioning from placental‐dependent fetal life to alveolar‐dependent newborn life. Human lung development and disease have been difficult to study due to the lack of an in vitro model system containing cells from the large airways and distal alveolus. This article describes a system that allows human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to differentiate and form three‐dimensional (3D) structures that emulate the development, cytoarchitecture, and function of the lung (“organoids”), containing epithelial and mesenchymal cell populations, and including the production of surfactant and presence of ciliated cells. The organoids can also be invested with mesoderm derivatives, differentiated from the same human pluripotent stem cells, such as alveolar macrophages and vasculature. Such lung organoids may be used to study the impact of environmental modifiers and perturbagens (toxins, microbial or viral pathogens, alterations in microbiome) or the efficacy and safety of drugs, biologics, and gene transfer. © 2020 Wiley Periodicals LLC. Basic Protocol: hESC/hiPSC dissection, definitive endoderm formation, and lung progenitor cell induction


title: COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?

text: Ibuprofen is an over-the-counter medication that is used widely for the treatment of pain and fever during COVID-19 pandemic. A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin–Angiotensin–Aldosterone system. ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease. At this time, there is no supporting evidence to discourage the use of ibuprofen.


docid: pejwnpmp

title: Pharmacists reinventing their roles to effectively respond to COVID-19: a global report from the international pharmacists for anticoagulation care taskforce (iPACT)

text: SARS-CoV2 is dramatically impacting the global population. Worldwide, pharmacists are changing their roles and being increasingly recognized for their role as essential service providers. This commentary provides some examples collected from Asia, Europe, the Americas and Africa, ranging from essential services to meet human rights basic needs, extended generalist services developed to ensure continuity of care and supply of essential medicines to the development of differentiated extended responsibilities in emergency care. All examples were collected using a network of pharmacists from 27 countries, representing various areas of pharmacy practice, education and research and outreaching to include patient advocates. Selected services illustrate good practice, capability to adapt and contribution to universal health coverage. Above all, it demonstrates the commitment and innovation of the pharmaceutical workforce in the fight against COVID-19.


title: Initial Real-Life Experience from a Designated COVID-19 Centre in Athens, Greece: a Proposed Therapeutic Algorithm

text: We report our initial experience with the management of a mixed group of patients with COVID-19 infection, admitted and treated in a designated COVID-19 centre in the Athens Metropolitan area over a 4-week period. The SARS-CoV-2 pandemic presented a huge challenge to the Greek National Healthcare System and healthcare workers. Their response so far has been miraculously effective. Since there are essentially no therapeutic guidelines yet for this disease, we relied mainly on our medical intuition, our empathy for our patients and team work to do the best possible for 49 people with this infection. We present the therapeutic algorithm we gradually developed (on the job) and applied in our patients, based on continuous creative brainstorming and monitoring of the literature.


title: COVID 19 and mask in sports

text: ABSTRACT Introduction: Due to the mandatory use of a mask, and the authorization to do outdoor sports in Catalonia, we try to assess the physiological impact of the hypercapnia hypoxia generated by the masks during aerobic sports practice. Methods: Eight subjects (2 women) were assessed at baseline with and without a mask, and then a 21-flex test was performed following the Ruffier protocol with a mask. Control of HR (heart rate), concentration of O2 and CO2 inside the mask and SatO2. The test was carried out in ambient air in squares in the city of Barcelona. Results: A decrease in O2 was recorded comparing the three conditions, baseline 20.9%, baseline mask 18.3%, post-exercise 17.8% (p <0.001). An increase in CO2 in the three preconditions (464, 14162, 17000 ppm; p <0.001). Basal saturation O2 was 97.6 ± 1.5% and post exercise 92.1 ± 4.12% (p 0.02). Conclusions: The use of masks in athletes causes hypoxic and hypercapnic breathing, being more evident in effort. The use of masks during a short exercise with an intensity around 6-8 METS, decreases O2 by 3.7% and increases the CO2 concentration by 20%.


title: Late histopathologic characteristics of critically ill COVID-19 patients: Different phenotypes without evidence of invasive aspergillosis, a case series

text: PURPOSE: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options. MATERIAL AND METHODS: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings. MEASUREMENT AND MAIN RESULTS: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis. CONCLUSIONS: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.


title: Chapter 11 Manufacturing Vaccines for an Emerging Viral Infection–Specific Issues Associated with the Development of a Prototype SARS Vaccine

text: Abstract The world was struck by surprise when a Severe Acute Respiratory Syndrome (SARS) epidemic started in 2003 in China. This disease had never been observed in man before; the SARS-Coronavirus causing the disease was unknown. With the uncertainty about the future impact of this epidemic, an important international collaboration started spontaneously sharing scientific knowledge and reagents. Resources became quickly available, and public and private efforts were undertaken to develop rapidly a vaccine. We will discuss here the importance of the international collaboration and the availability of funding. Moreover, we will review the most important and challenging steps during the industrial development of the SARS vaccine highlighting the difficulties in terms of safety working with such a highly pathogenic, unknown virus. We will emphasize the industrial perspectives on inactivation and decontamination experiments, the selection of the most promising vaccine candidate, the production process and the choice and use of animal models in such a pressing and difficult situation. Finally, we will briefly review the unique regulatory environment created during this period for the development of a SARS vaccine.


title: A New Bat-HKU2–like Coronavirus in Swine, China, 2017

text: We identified from suckling piglets with diarrhea in China a new bat-HKU2–like porcine coronavirus (porcine enteric alphacoronavirus). The GDS04 strain of this coronavirus shares high aa identities (>90%) with the reported bat-HKU2 strains in Coronaviridae-wide conserved domains, suggesting that the GDS04 strain belongs to the same species as HKU2.


title: A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism

text: BACKGROUND: SARS coronavirus main proteinase (SARS CoVMpro) is an important enzyme for the replication of Severe Acute Respiratory Syndrome virus. The active site region of SARS CoVMpro is divided into 8 subsites. Understanding the binding mode of SARS CoVMpro with a specific substrate is useful and contributes to structural-based drug design. The purpose of this research is to investigate the binding mode between the SARS CoVMpro and two octapeptides, especially in the region of the S3 subsite, through a molecular docking and molecular dynamics (MD) simulation approach. RESULTS: The one turn α-helix chain (residues 47–54) of the SARS CoVMpro was directly involved in the induced-fit model of the enzyme-substrate complex. The S3 subsite of the enzyme had a negatively charged region due to the presence of Glu47. During MD simulations, Glu47 of the enzyme was shown to play a key role in electrostatic bonding with the P3Lys of the octapeptide. CONCLUSION: MD simulations were carried out on the SARS CoVMpro-octapeptide complex. The hypothesis proposed that Glu47 of SARS CoVMpro is an important residue in the S3 subsite and is involved in binding with P3Lys of the octapeptide.