title: Sources of Information and Health Beliefs Related to SARS and Avian Influenza among Chinese Communities in the United Kingdom and The Netherlands, Compared to the General Population in these Countries

text: BACKGROUND: Ethnic minorities in Europe such as the Chinese may need a special strategy with regard to risk communication about emerging infectious diseases. To engage them in precautionary actions, it is important to know their information sources, knowledge, and health beliefs. PURPOSE: This study’s purpose is to study the use of information sources, knowledge, and health beliefs related to SARS and avian flu of Chinese people in the UK and The Netherlands, and to make comparisons with the general population in these countries. METHOD: Results of a self-administered questionnaire among 300 British/Dutch Chinese were compared to data obtained from a computer-assisted phone survey among the general population (n = 800). RESULTS: British/Dutch Chinese got most information about emerging diseases from family and friends, followed by Chinese media and British/Dutch TV. They had less confidence than general groups in their doctor, government agencies, and consumer/patient interest groups. Their knowledge of SARS was high. They had a lower perceived threat than general populations with regard to SARS and avian flu due to a lower perceived severity. They had higher self-efficacy beliefs regarding SARS and avian flu. CONCLUSION: In case of new outbreaks of SARS/avian flu in China, local authorities in the UK and The Netherlands can best reach Chinese people through informal networks and British/Dutch TV, while trying to improve confidence in information from the government. In communications, the severity of the disease rather than the susceptibility appears to need most attention.


title: OT-1 Mice Display Minimal Upper Genital Tract Pathology Following Primary Intravaginal Chlamydia muridarum Infection

text: Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide and leads to serious pathological sequelae in the upper genital tract (UGT) including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several components of the host immune responses have been shown to contribute to the UGT pathology following genital chlamydial infection. We have shown recently that CD8(+) T cells induce the chlamydial UGT pathology via the production of TNF-α. However, those studies did not determine whether the pathology is mediated by bystander or antigen-specific CD8(+) T cells. In this study, we compared chlamydial clearance and UGT pathology in OT-1 transgenic mice and the corresponding C57BL/6J wild type mice following primary intravaginal C. muridarum infection. All CD8(+) T cells in the OT-1 mice respond only to the Ova 257–264 peptide and are incapable of responding to other antigenic epitopes including those of Chlamydia. OT-1 mice displayed vaginal chlamydial clearance comparable to the wild type animals. However, both oviduct and uterine horn pathology were minimal in the OT-1 mice compared to the high degree of pathology observed in the wild type animals. These results strongly suggest that Chlamydia-specific, not bystander, CD8(+) T cells mediate the UGT pathological sequelae following genital chlamydial infection.


Extensión y cuantificación de la carga inflamatoria en COVID-19 mediante tomografía computarizada


title: Central statistical monitoring of investigator-led clinical trials in oncology

text: Investigator-led clinical trials are pragmatic trials that aim to investigate the benefits and harms of treatments in routine clinical practice. These much-needed trials represent the majority of all trials currently conducted. They are however threatened by the rising costs of clinical research, which are in part due to extensive trial monitoring processes that focus on unimportant details. Risk-based quality management focuses, instead, on “things that really matter”. We discuss the role of central statistical monitoring as part of risk-based quality management. We describe the principles of central statistical monitoring, provide examples of its use, and argue that it could help drive down the cost of randomized clinical trials, especially investigator-led trials, whilst improving their quality.


title: Comparison of the prevalence of respiratory viruses in patients with acute respiratory infections at different hospital settings in North China, 2012–2015

text: BACKGROUND: Acute respiratory infections (ARIs) are a great public health challenge globally. The prevalence of respiratory viruses in patients with ARIs attending at different hospital settings is fully undetermined. METHODS: Laboratory-based surveillance for ARIs was conducted at inpatient and outpatient settings of 11 hospitals in North China. The first 2–5 patients with ARIs were recruited in each hospital weekly from 2012 through 2015. The presence of respiratory viruses was screened by PCR assays. The prevalence of respiratory viruses was determined and compared between patients at different hospital settings. RESULTS: A total of 3487 hospitalized cases and 6437 outpatients/Emergency Department (ED) patients were enrolled. The most commonly detected viruses in the hospitalized cases were respiratory syncytial virus (RSV, 33.3%) in children less than two years old, adenoviruses (13.0%) in patients 15–34 years old, and influenza viruses (IFVs, 9.6%) in patients ≥65 years. IFVs were the most common virus in outpatient/ED patients across all age groups (22.7%). After controlling for the confounders caused by other viruses and covariates, adenoviruses (adjusted odds ratio [aOR]: 3.97, 99% confidence interval [99% CI]: 2.19–7.20) and RSV (aOR: 2.04, 99% CI: 1.34–3.11) were independently associated with increased hospitalization in children, as well as adenoviruses in adults (aOR: 2.14, 99% CI: 1.19–3.85). Additionally, co-infection of RSV with IFVs was associated with increased hospitalization in children (aOR: 12.20, 99% CI: 2.65–56.18). CONCLUSIONS: A substantial proportion of ARIs was associated with respiratory viruses in North China. RSV, adenoviruses, and co-infection of RSV and IFVs were more frequent in hospitalized children (or adenoviruses in adults), which might predict the severity of ARIs. Attending clinicians should be more vigilant of these infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-2982-3) contains supplementary material, which is available to authorized users.


title: Antiviral activity of Rheum palmatum methanol extract and chrysophanol against Japanese encephalitis virus

text: Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC(50) = 15.04 μg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC(50) = 51.41 μg/ml). Meanwhile, IC(50) values determined by plaque reduction assay were 15.82 μg/ml for chrysophanol and 17.39 μg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC(50) values were 7.58 μg/ml for methanol extract, 17.36 μg/ml for water extract, 0.75 μg/ml for chrysophanol and 0.46 μg/ml for aloe-emodin, respectively. In addition, 10 μg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.


title: ‘Reflections on frontline medical work during Covid‐19, and the embodiment of risk’

text: Drawing on the voice of a woman NHS frontline Doctor during the current Covid‐19 pandemic, we explore her lived experience of the embodiment of risk in the crisis. We explore her struggles and difficulties, giving her voice, and mobilising our writing to listen to these experiences, reflecting on them as a way of living our own feminist lives. Her story illustrates that the current crisis is not only a crisis of health, but a crisis for feminism. Through telling her story, we cast light upon the embodied amplification of inequalities, paternalistic discourses around risk, and lived experience of exposure to risk of contracting a deadly virus. We explore her work on the NHS frontline, providing a conceptual framework of the multi‐level facets of the embodiment of risk, through lived experiences of risk, and observations of the inequality of risk in the context of the Covid‐19 pandemic in the UK.


title: Estimation of incubation period and generation time based on observed length‐biased epidemic cohort with censoring for COVID‐19 outbreak in China

text: The incubation period and generation time are key characteristics in the analysis of infectious diseases. The commonly used contact‐tracing based estimation of incubation distribution is highly influenced by the individuals' judgment on the possible date of exposure, and might lead to significant errors. On the other hand, interval censoring based methods are able to utilize a much larger set of traveling data but may encounter biased sampling problems. The distribution of generation time is usually approximated by observed serial intervals. However, it may result in a biased estimation of generation time, especially when the disease is infectious during incubation. In this paper, the theory from renewal process is partially adopted by considering the incubation period as the inter‐arrival time, and the duration between departure from Wuhan and onset of symptoms as the mixture of forward time and inter‐arrival time with censored intervals. In addition, a consistent estimator for the distribution of generation time based on incubation period and serial interval is proposed for incubation‐infectious diseases. A real case application to the current outbreak of COVID‐19 is implemented. We find that the incubation period has a median of 8.50 days (95% CI: 7.22, 9.15). The basic reproduction number in the early phase of COVID‐19 outbreak based on the proposed generation time estimation is estimated to be 2.96 (95% CI: 2.15, 3.86). This article is protected by copyright. All rights reserved


docid: bkyxpffu

title: Early network properties of the COVID-19 pandemic – the Chinese scenario

text: OBJECTIVES: To control epidemics, sites more affected by mortality should be identified. METHODS: Defining epidemic nodes as areas that included both most fatalities per time unit and connections, such as highways, geo-temporal Chinese data on the COVID-19 epidemic were investigated with linear, logarithmic, power, growth, exponential, and logistic regression models. A z-test compared the slopes observed. RESULTS: Twenty provinces suspected to act as epidemic nodes were empirically investigated. Five provinces displayed synchronicity, long-distance connections, directionality and assortativity – network properties that helped discriminate epidemic nodes. The rank I node included most fatalities and was activated first. Fewer deaths were reported, later, by rank II and III nodes While the data from rank I-III nodes exhibited slopes, the data from the remaining provinces did not. The power curve was the best fitting model for all slopes. Because all pairs (rank I vs. rank II, rank I vs. rank III, and rank II vs. rank III) of epidemic nodes differed statistically, rank I-III epidemic nodes were geo-temporally and statistically distinguishable. CONCLUSIONS: The geo-temporal progression of epidemics seems to be highly structured. Epidemic network properties can distinguish regions that differ in mortality. This real-time geo-referenced analysis can inform both decision-makers and clinicians.


docid: ueuemeil

title: Hidden Costs of Biodefense Research


title: Fc receptors in antibody‐dependent enhancement of viral infections

text: Sensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody‐dependent enhancement (ADE) of infection, the phenomenon occurs when virus‐antibody immunocomplexes interact with cells bearing complement or Fc receptors, promoting internalization of the virus and increasing infection. Frequently associated with exacerbation of viral disease, ADE of infection presents a major obstacle to the prevention of viral disease by vaccination and is thought to be partly responsible for the adverse effects of novel antiviral therapeutics such as intravenous immunoglobulins. There is a growing body of work examining the intracellular signaling pathways and epitopes responsible for mediating ADE, with a view to aiding rational design of antiviral strategies. With in vitro studies also confirming ADE as a feature of infection for a growing number of viruses, challenges remain in understanding the multilayered molecular mechanisms of ADE and its effect on viral pathogenesis.


title: Obstetrics Risk Assessment: Evaluation of Selection Criteria for Vaccine Research Studies in Pregnant Women

text: Vaccines designed for use in pregnancy and vaccine trials specifically involving pregnant women are rapidly expanding. One of the key challenges in designing maternal immunization trials is that developing exclusion criteria requires understanding and quantifying the background risk for adverse pregnancy outcomes in the pregnancy being studied, which can occur independent of any intervention and be unrelated to vaccine administration. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed and published case definitions and guidelines for data collection, analysis, and evaluation of maternal immunization safety in trials involving pregnant women. Complementing this work, we sought to understand how to best assess obstetric risk of adverse outcomes and differentiate it from the assessment of vaccine safety. Quantification of obstetric risk is based on prior and current obstetric, and maternal medical history. We developed a step-wise approach to evaluate and quantify obstetric and maternal risk factors in pregnancy based on review of published literature and guidelines, and critically assessed these factors in the context of designing inclusion and exclusion criteria for maternal vaccine studies. We anticipate this risk assessment evaluation may assist clinical trialists with study design decisions, including selection of exclusion criteria for vaccine trials involving pregnant women, consideration of sub-group classification, such as high or low risk subjects, or schedule considerations, such as preferred trimester of gestation for an intervention during pregnancy. Additionally, this tool may be utilized in data stratification at time of study analyses.


title: Low-level contamination of deoxynivalenol: A threat from environmental toxins to porcine epidemic diarrhea virus infection

text: Mycotoxins are toxic metabolites produced by fungal species that commonly present in the global environment, especially in cereals and animal forages. The changing global environment may further increase the exposure to these toxins, posing a serious threat to humans and animals. Recently, coronavirus has become one of the most important pathogens threatening human and animal health. It is not clear whether environmental toxins, such as mycotoxins, will affect coronavirus infection. Given that pigs are among the animals most affected by coronavirus and highly homologous to humans, weaned piglets and IPEC-J2 cells were respectively chosen as in vivo and in vitro model to explore the impacts of deoxynivalenol (DON), the most abundant trichothecene mycotoxin in feed, on porcine epidemic diarrhea virus (PEDV) infection and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 μg/kg DON, respectively. Significant increases in the diarrhea rates, gut barrier injury and PEDV proliferation of piglets’ small intestine were observed in experimental groups compared with the control. Additionally, the autophagosome-like vesicles and the autophagy-related proteins expression were also increased in experimental groups. In vitro, we observed that 0.1, 0.5 and 1.0 μM DON significantly promoted the entry and replication of PEDV in IPEC-J2 cells, along with the induction of a complete autophagy. CRISPR‐Cas9‐mediated knockout of LC3B indicated a vital role of autophagy in the promotion. Pretreatment with p38 signaling inhibitor could significantly block the induction of autophagy, indicating that DON could promote the PEDV infection by triggering p38-mediated autophagy. Our findings suggest that mycotoxin could influence the prevalence of coronavirus and provide new ideas for the prevention and control of coronavirus.


title: Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting

text: A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.


title: 7 Antisense Oligonucleotides and RNA Interference

text: Antisense technology presents an opportunity to manipulate gene expression within the cells to treat various diseases, and acts as a powerful tool for studying gene function utilizing antisense agents to manage the diseases by regulating the expression of the specific factor that actually causes the particular disease. Highly specific and effective gene silencing of any disease can be achieved by an accurate knowledge of the target mRNA sequence and rational design of its complementary antisense agents for the downregulation of its protein message. This technology has been successfully used for the treatment of cancer, HIV, and other mutating viral diseases. The technology uses agents like antisense oligonucleotides, ribozymes, short interfering RNA (siRNA), microRNA (miRNA), apatamers, and others. The purpose of this chapter is to survey different antisense technologies and the various mechanisms of gene silencing. The chapter also highlights therapeutic limitations, benefits, clinical applications, and various advances to meet delivery challenges of these agents, and gives due consideration to the regulatory and patent aspects.


title: Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era

text: AIMS: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). METHODS AND RESULTS: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). CONCLUSION: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.


title: Genome replication/expression strategies of positive-strand RNA viruses: A simple version of a combinatorial classification and prediction of new strategies

text: A combinatorial approach to the classification of replication/expression strategies of positive-strand RNA virus genomes is suggested. Eighteen genome strategies defined as combinations of distinct modes of expression and replication are briefly characterized, 10 of which have been actually found in diverse virus groups. The chances for realization of the remaining eight strategies are evaluated. It is demonstrated that positive-strand RNA virus genome strategies are not necessarily monophyletic characters and could, in some cases, evolve convergently.


docid: gjctfjub

title: Neurological manifestations and complications of COVID-19: A Literature Review

text: Abstract The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2109 and rapidly spread to more than 200 countries as a global health pandemic. There are more than 2.3 million confirmed cases and around 165,000 fatalities. The primary manifestation is respiratory and cardiac but neurological features are also being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.


title: You're only as young as your immune system

text: There has never been a more important time to keep your immune system fit and healthy. And as Graham Lawton discovers, there are now ways to keep it younger than you are


Etymologia: Coronavirus


title: Early Experience With COVID-19 and Solid Organ Transplantation at a US High-volume Transplant Center

text: The novel coronavirus SARS-CoV-2 [coronavirus disease 2019 (COVID-19)] poses unique challenges for immunosuppressed patients. Solid organ transplant (SOT) recipients comprise a large proportion of this group, yet there is limited knowledge about the presentation, clinical course, and immunosuppression management of this novel infection among heart, lung, liver, pancreas, and kidney transplant recipients. METHODS. We present 21 SOT recipients diagnosed with COVID-19 between January 1, 2020 and April 22, 2020 at a US high-volume transplant center. Diagnostic workup, clinical course, immunosuppression/antiviral management, and immediate outcomes are described. RESULTS. Twenty-one (15.9%) of 132 symptomatic patients tested were positive. Mean age at diagnosis was 54.8 ± 10.9 years. Median time from transplant was 5.58 years (interquartile range 2.25, 7.33). Median follow-up was 18 days (interquartile range 13, 30). Fourteen patients required inpatient management, with 7 (50%) placed in the intensive care unit (ICU). All transplant types were represented. Nearly 43% exhibited GI symptoms. Over half (56.2%) presented with elevated serum creatinine suggestive of acute kidney injury. The majority of patients (5/7) with concomitant infections at baseline required the ICU. Eighty percent received hydroxychloroquine ± azithromycin. Ten received toclizumab and/or ribavirin; 1 received remdesivir. Antimetabolites ± calcineurin inhibitors were held or reduced. Over half of hospitalized patients (8/14) were discharged home. Only 1 mortality (4.8%) to date, in a critically ill heart/kidney patient who had been in the ICU before diagnosis. CONCLUSION. COVID-19 positive SOT at our institution had favorable short-term outcomes. Those with concomitant infections had more severe illness. More data will be available to evaluate long-term outcomes and disease impact on graft function.


title: The COVID-19 Catalyst: Analysis of a Tertiary Academic Institution’s Rapid Assimilation of Telemedicine

text: INTRODUCTION: The COVID-19 pandemic forced all urology practices to reconsider the necessity of face-to-face office encounters. Seeking to reduce patient exposure, our urologic oncology office made an immediate transition to telemedicine and this study reports our experience. METHODS: Beginning March 17, 2020 the urologic oncology department committed to see all patients via telemedicine, unless they needed a cystoscopy for high grade urothelial cell carcinoma or recent gross hematuria, or required removal of a Foley catheter or surgical drain. March 17 was assigned day 1, and for the next 14 days rates of face-to-face, audio and audiovisual encounters were recorded. A telephone survey was conducted with all patients who participated in an audiovisual encounter. RESULTS: In analyzing the numbers of face-to-face, audio and audiovisual encounters, after day 5 more patients participated in audiovisual encounters than any other modality. By day 10 no nonessential face-to-face encounter occurred. There was an 80.4% response rate to our survey. Average patient account setup time was 10.5 minutes and 35.1% required assistance from our office to set up their account, averaging 7.1 minutes. No-show rates of face-to-face encounters were significantly higher than for audiovisual encounters (face-to-face 67%, audiovisual 17%, p <0.001). Overall 82% of patients surveyed were likely to elect for a telemedicine encounter over a face-to-face encounter for a routine visit during future flu seasons. CONCLUSIONS: The current study describes the initial adoption, early clinical experience and patient impressions of rapid implementation of telemedicine during the COVID-19 pandemic.


title: Host Tissue and Glycan Binding Specificities of Avian Viral Attachment Proteins Using Novel Avian Tissue Microarrays

text: The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.


title: Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments

text: Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.


docid: bipaceqy

title: Medical issues associated with commercial flights

text: Summary Almost 2 billion people travel aboard commercial airlines every year. Health-care providers and travellers need to be aware of the potential health risks associated with air travel. Environmental and physiological changes that occur during routine commercial flights lead to mild hypoxia and gas expansion, which can exacerbate chronic medical conditions or incite acute in-flight medical events. The association between venous thromboembolism and long-haul flights, cosmic-radiation exposure, jet lag, and cabin-air quality are growing health-care issues associated with air travel. In-flight medical events are increasingly frequent because a growing number of individuals with pre-existing medical conditions travel by air. Resources including basic and advanced medical kits, automated external defibrillators, and telemedical ground support are available onboard to assist flight crew and volunteering physicians in the management of in-flight medical emergencies.


title: Optimal professional development ICT training initiatives at flagship universities

text: This study explores best practices and roles of information and communication technology (ICT) in select professional development centers at 16 flagship universities. Through adopting a qualitative case study design, this study explores the strengths and weaknesses of current technology training initiatives in the selected professional development centers. As part of the research and teaching programs at flagship universities, professional development center leaders shared about the current ICT practices as well as the strengths and limitations of their own centers. The analysis section includes a critical look at ICT practices among flagship universities from a human resource theory lens. Findings indicate common successes that facilitate the ICT practices of these centers including delivery mediums, services, ideas, and goals, as well as various barriers of implementing ICT training initiatives. The paper concludes with suggestions on how professional development center leaders, senior administrators, and educational policy makers can help improve professional development processes with the assistance of optimal ICT initiatives.


Lamp for tadpoles


title: COVID‐19 and gastrointestinal endoscopies: current insights and emergent strategies

text: A new coronavirus emerged in December 2019 in Wuhan city of China, named as the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), and disease was called as coronavirus disease‐2019 (COVID‐19). The infection due to this virus spread exponentially throughout China and then spread across >205 nations, including the United States (US). Gastrointestinal (GI) endoscopies are routinely performed in the US and globally. Previous reports of isolated infection outbreaks were reported with endoscopes acting as potential vectors. While multidrug‐resistant organisms have been reported to be spread by endoscopes, few cases of viruses such as Hepatitis B and C are noted in the literature. COVID‐19 predominately spread by droplet transmission, although recent evidence showed that shedding in feces and feco‐oral transmission could also be possible. It is unclear if COVID‐19 could be transmitted by endoscopes, but it could theoretically happen due to contact with mucous membranes and body fluids. GI endoscopies involve close contact with oral and colonic contents exposing endoscopy staff to respiratory and oropharyngeal secretions. This can increase the risk of contamination and contribute to virus transmission. Given these risks, all major GI societies have called for rescheduling elective non‐urgent procedures and perform only emergent or urgent based on the clinical need. Furthermore, pre‐screening of all individuals prior to endoscopy is recommended. This article focuses on the risk of COVID‐19 transmission by GI shedding, the potential role of endoscopes as a vector of this novel virus including transmission during endoscopies and prevention strategies including deferral of elective non‐urgent endoscopy procedures.


title: New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study

text: Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID‐19). This multicenter retrospective study enrolled people with COVID‐19 from January 18 to February 18, 2020 at 42 government‐designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizurelike symptoms during hospitalization due to acute stress reaction and hypocalcemia, and 84 (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures. There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID‐19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID‐19.


Industrial seafood systems in the immobilizing COVID-19 moment


title: Cyclophilins and cyclophilin inhibitors in nidovirus replication

text: Abstract Cyclophilins (Cyps) belong to the family of peptidyl-prolyl isomerases (PPIases). The PPIase activity of most Cyps is inhibited by the immunosuppressive drug cyclosporin A and several of its non-immunosuppressive analogs, which can also block the replication of nidoviruses (arteriviruses and coronaviruses). Cyclophilins have been reported to play an essential role in the replication of several other RNA viruses, including human immunodeficiency virus-1, hepatitis C virus, and influenza A virus. Likewise, the replication of various nidoviruses was reported to depend on Cyps or other PPIases. This review summarizes our current understanding of this class of nidovirus-host interactions, including the potential function of in particular CypA and the inhibitory effect of Cyp inhibitors. Also the involvement of the FK-506-binding proteins and parvulins is discussed. The nidovirus data are placed in a broader perspective by summarizing the most relevant data on Cyp interactions and Cyp inhibitors for other RNA viruses.


Analysis of Gastrointestinal and Hepatic Manifestations of SARS-CoV-2 Infection in 892 patients in Queens, NY


docid: jjluocxz

title: Virus-like particle-based vaccines for animal viral infections

text: Vaccination is considered one of the most effective ways to control pathogens and prevent diseases in humans as well as in the veterinary field. Traditional vaccines against animal viral diseases are based on inactivated or attenuated viruses, but new subunit vaccines are gaining attention from researchers in animal vaccinology. Among these, virus-like particles (VLPs) represent one of the most appealing approaches opening up interesting frontiers in animal vaccines. VLPs are robust protein scaffolds exhibiting well-defined geometry and uniformity that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines; nevertheless, only one veterinary VLP-base vaccine is licensed. Here, we review and examine in detail the current status of VLPs as a vaccine strategy in the veterinary field, and discuss the potential advantages and challenges of this technology.


P.062 Human coronavirus NL63 and 229E seroconversion in children


title: Can a toilet promote virus transmission? From a fluid dynamics perspective

text: Currently, a novel coronavirus named “SARS-CoV-2” is spreading rapidly across the world, causing a public health crisis, economic losses, and panic. Fecal–oral transmission is a common transmission route for many viruses, including SARS-CoV-2. Blocking the path of fecal–oral transmission, which occurs commonly in toilet usage, is of fundamental importance in suppressing the spread of viruses. However, to date, efforts at improving sanitary safety in toilet use have been insufficient. It is clear from daily experience that flushing a toilet generates strong turbulence within the bowl. Will this flushing-induced turbulent flow expel aerosol particles containing viruses out of the bowl? This paper adopts computational fluid dynamics to explore and visualize the characteristics of fluid flow during toilet flushing and the influence of flushing on the spread of virus aerosol particles. The volume-of-fluid (VOF) model is used to simulate two common flushing processes (single-inlet flushing and annular flushing), and the VOF–discrete phase model (DPM) method is used to model the trajectories of aerosol particles during flushing. The simulation results are alarming in that massive upward transport of virus particles is observed, with 40%–60% of particles reaching above the toilet seat, leading to large-scale virus spread. Suggestions concerning safer toilet use and recommendations for a better toilet design are also provided.


title: Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia

text: STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels. METHODS: This prospective, multicenter study was carried out in the most important children’s hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease. RESULTS: CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%). CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard.


title: Human adenovirus in nasopharyngeal and blood samples from children with and without respiratory tract infections

text: Abstract Background Human adenovirus (HAdV) is a double-stranded DNA virus associated with respiratory tract infections (RTI) in children. Using polymerase chain reaction (PCR) tests, HAdV often is detected together with other virus species, even in healthy controls. Objectives The aim of this study was to compare molecular detection of HAdV with culture, and to examine the associations of various methods to RTI. Study design Nasopharyngeal aspirates (NPA) were collected from 4319 children admitted with RTI and from 361 controls. The NPAs were examined for 23 viral and bacterial pathogens, using inhouse real-time PCR-assays based on TaqMan probes, in addition to bacterial and viral culture. HAdV concentration was evaluated semi-quantitatively from the Ct-value and quantitatively by use of ADENOVIRUS R-gene®. Results HAdV-DNA was detected in 6.1% patient samples and in 10.5% controls (p< 0.001). Compared to controls, patients had an OR of 3.8 (95% CI 1.4–10.3) for mono-detection of HAdV DNA, and an OR of 5.1 (95% CI 2.0–13.4) for HAdV-positive samples grew adenovirus by culture. HAdV DNA loads from children with RTI consisted of two clusters: one cluster with high viral loads (Ct < 30 and >106 copies/ml) and one cluster with low viral loads, whereas among the controls, nearly all had low viral loads (OR 7.8, 95% CI 2.2–27.1). In 61 available plasma samples, 16.4% were positive for HAdV DNA, all were from patients. Conclusion The detection of HAdV DNA per se by qualitative PCR is not useful as a diagnostic test. Detection of HAdV by use of viral culture and a high viral HAdV DNA load are the two methods most strongly associated with RTI in children.


title: What are the main patient safety concerns of healthcare stakeholders: a mixed-method study of Web-based text

text: Abstract Objectives Various healthcare stakeholders define quality of care in different ways. Public policy could advocate all these concerns. This study was conducted to identify the main themes on patient safety of stakeholders expressed before and after the Patient Safety Act was enacted in Korea in 2015. Design Longitudinal observational study of the interests of healthcare stakeholders generated between January 2014 and September 2018. Materials and methods Text data were collected from 2,487 documents on 18 websites that were identified as representative healthcare stakeholder groups of consumers, providers, government, and researchers. A Korean natural language processing (NLP) package, manual review, and synonym dictionary were used for data preprocessing, and we adopted the unsupervised NLP method of probabilistic topic modeling and latent Dirichlet allocation. A linear trend analysis over time, a qualitative step involving two external experts, and original text reviews were performed to validate the identified topics. Results Forty-one topics were identified, and the most common concerns of stakeholders were institutional infection control as triggered by the Middle East respiratory syndrome outbreak in early 2015, and infusion-related infection from late 2017 until the middle of 2018. The other top-three concerns of the stakeholder groups were highly similar, while research topics were limited to the perceptions of providers and the activities and culture of hospitals. Five topics showed statistically significant increasing trends over time, while another five showed decreasing trends (both P < 0.05). In the qualitative step, we confirmed 35 themes and revised the other 6. Conclusions A common concern among stakeholders was hospital infection control, ranging from nosocomial infections to those brought in by family visiting patients. Government policies and systemic approaches to patient safety were highlighted by different stakeholders. Researchers were focused on hospital sociocultural factors at both the organizational and clinician levels. These identified concerns all should be advocated by the public health policy.


title: Increase in COVID‐19 cases and case‐fatality and case‐recovery rates in Europe: A cross‐temporal meta‐analysis

text: The new coronavirus (COVID‐19) infection reported in China in December 2019 has become a pandemic in a few weeks, affecting the entire world. In this respect, it is crucial to determine the case‐increase, case‐fatality, and case‐recovery rates to control COVID‐19. In this study, the case‐increase, case‐fatality, and case‐recovery rates of COVID‐19 in 36 European countries were analyzed with the meta‐analysis method using data released by the health organizations and WHO. The data were obtained from the website of health organizations of 36 European countries and the website of WHO until 11 May 2020. The analyses were carried out on 1 744 704 COVID‐19‐diagnosed cases in 36 European countries. The case‐increase, case‐fatality and case‐recovery rates of COVID‐19 were calculated using 95% confidence intervals (95% CI), single‐arm meta‐analysis, cross‐temporal meta‐analysis, and meta‐regression random‐effects model. The standardized case‐increase rate of COVID‐19 is 5% (95% CI [0.040, 0.063]) and the average case‐increase rate in European countries has started to decline by around 3% (95% CI [0.047, 0.083]) weekly. The countries with the highest rate of case increase are Belgium, Sweden, Russia, the Netherlands and the United Kingdom. Although the case‐fatality rate of COVID‐19 patients was 4.5% as of May 11 (95% CI [0.037‐0.055]), this rate is 6.3% (95% CI [0.047, 0.083]) in standardized time (6th week). The case‐recovery rates of patients are 46% (95% CI [0.376‐0.547]). This study presents important results regarding the COVID‐19 pandemic in Europe. Although the rate of increase in new COVID‐19 cases has dropped, there is not much decline in the case‐fatality rates and no increase in case‐recovery rates. The case‐fatality rate of COVID‐19 in Europe was estimated to be in the range of 4% to 4.5% and a minimum of 4 weeks (as of 11 May) is expected to have the figure below 1% in a country with an average case‐increase rate. Monitoring case fatalities in Belgium, the Netherlands and Sweden, and treatment successes in Germany and Austria play a role of utmost importance.


Correction to Lancet Respir Med 2020; 8: 506–17


docid: ubwkklvx

title: Severe acute respiratory syndrome coronavirus infection in children


title: Strategies for vaccine design for corona virus using Immunoinformatics techniques

text: The cutting-edge technology vaccinomics is the combination of two topics immunogenetics and immunogenomics with the knowledge of systems biology and immune profiling for designing vaccine against infectious disease. In our present study, an epitope-based peptide vaccine against nonstructural protein 4 of beta coronavirus, using a combination of B cell and T cell epitope predictions, followed by molecular docking methods are performed. Here, protein sequences of homologous nonstructural protein 4 of beta coronavirus are collected and conserved regions present in them are investigated via phylogenetic study to determine the most immunogenic part of protein. From the identified region of the target protein, the peptide sequence IRNTTNPSAR from the region ranging from 38-47 and the sequence PTDTYTSVYLGKFRG from the positions of 76-90 are considered as the most potential B cell and T cell epitopes respectively. Furthermore, this predicted T cell epitopes PTDTYTSVY and PTDTYTSVYLGKFRG interacted with MHC allelic proteins HLA-A*01:01 and HLA-DRB5*01:01 respectively with the low IC50 values. These epitopes are perfectly fitted into the epitope binding grooves of alpha helix of MHC I molecule and MHC II molecule with binding energy scores −725.0 Kcal/mole and −786.0 Kcal/mole respectively, showing stability in MHC molecules binding. This MHC restricted epitope PTDTYTSVY also showed a good conservancy of 50.16% in world population coverage. This MHC I HLA-A*01:01 allele is present among 58.87% of Chinese population also. Therefore, the epitopes IRNTTNPSAR and PTDTYTSVYLGKFRG may be considered as potential peptides for peptide-based vaccine for coronavirus after further experimental study.


title: A letter of solidarity during the COVID‐19 Pandemic

text: The coronavirus disease (COVID‐19) pandemic has had a substantial impact on the lives of most of the worlds’ population. We are aware that for liver disease patients this has been especially concerning. The editorial from Sun and colleagues [1] provides an overview of the major challenges facing liver specialists as they strive to deliver essential services, and highlights some of the critical research gaps around COVID‐19 and liver disease.


title: Ratcheting down the virulence of SARS‐CoV‐2 in the COVID‐19 pandemic

text: Muller's Ratchet predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms. This article is protected by copyright. All rights reserved.


title: Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats

text: This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi‐institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment.


title: Cellular Interactions of Liposomes and PISA Nanoparticles during Human Blood Flow in a Microvascular Network

text: A key concept in nanomedicine is encapsulating therapeutic or diagnostic agents inside nanoparticles to prolong blood circulation time and to enhance interactions with targeted cells. During circulation and depending on the selected application (e.g., cancer drug delivery or immune modulators), nanoparticles are required to possess low or high interactions with cells in human blood and blood vessels to minimize side effects or maximize delivery efficiency. However, analysis of cellular interactions in blood vessels is challenging and is not yet realized due to the diverse components of human blood and hemodynamic flow in blood vessels. Here, the first comprehensive method to analyze cellular interactions of both synthetic and commercially available nanoparticles under human blood flow conditions in a microvascular network is developed. Importantly, this method allows to unravel the complex interplay of size, charge, and type of nanoparticles on their cellular associations under the dynamic flow of human blood. This method offers a unique platform to study complex interactions of any type of nanoparticles in human blood flow conditions and serves as a useful guideline for the rational design of liposomes and polymer nanoparticles for diverse applications in nanomedicine.


title: Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse

text: The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.


title: A fractionally integrated autoregressive moving average approach to forecasting tourism demand

text: The primary aim of this paper is to incorporate fractionally integrated ARMA (p, d, q) (ARFIMA) models into tourism forecasting, and to compare the accuracy of forecasts with those obtained by previous studies. The models are estimated using the volume of monthly international tourist arrivals in Singapore. Empirical findings demonstrate the evidence that the approach we propose generates relatively lower sample mean absolute percentage errors (MAPEs). This study also deals with the volatile data faced by a forecaster. We use the Asian financial crisis and the September 11 event as examples of economic and political shocks. With respect to the objective of shaving the coefficient MAPE, forecasts based on the selected ARFIMA models dominate convincingly.


The COVID‐19 pandemic: Is it a “Black Swan”? Some risk management challenges in common with chemical process safety


title: Epidemiology and causes of preterm birth

text: Summary This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.


Nosology expansion: not always for health’s sake


docid: rjglqmfd

title: Protective roles of Cordyceps on lung fibrosis in cellular and rat models

text: Abstract Ethnopharmacological relevance Cordyceps sinensis is a fungus used in traditional Chinese medicine as a tonic to soothe the lung for the treatment of fatigue and respiratory diseases. Idiopathic pulmonary fibrosis is a chronic, irreversible and debilitating lung disease showing fibroblast/myofibroblast expansion and excessive deposition of extracellular matrix in the interstitium leading to breathing difficulty. Our previous observation revealed a partial relief of lung fibrosis in patients suffering from severe acute respiratory syndrome (SARS). We hypothesize that Cordyceps has beneficial effects on lung fibrosis and the objective of this study is to explore the target(s) of Cordyceps in the relief of lung fibrosis in animal and cell models and to gain insight into its underlying mechanisms. Material and methods A rat model of bleomycin (BLM)-induced lung fibrosis and a fibrotic cell model with transforming growth factor beta-1 induction were employed in the studies. Results Reduction of infiltration of inflammatory cells, deposition of fibroblastic loci and collagen, formation of reactive oxygen species, and production of cytokines, as well as recovery from imbalance of MMP-9/TIMP-1, were observed in fibrotic rats after treatment with Cordyceps in preventive (from the day of BLM administration) and therapeutic (from 14 days after BLM) regimens. In a fibrotic cell model with transforming growth factor beta-1 induction, the human lung epithelial A549 acquired a mesenchymal phenotype and an increase of vimentin expression with a concomitant decrease of E-cadherin. This epithelial–mesenchymal transition could be partially reverted by cordycepin, a major component of Cordyceps. Conclusion The findings provide an insight into the preventive and therapeutic potentials of Cordyceps for the treatment of lung fibrosis.


title: Coronavirus (COVID-19) Fulminant Myopericarditis and Acute Respiratory Distress Syndrome (ARDS) in a Middle-Aged Male Patient

text: Myopericarditis remains a prominent infectious inflammatory disorder throughout a patient’s lifetime. Moreover, viral pathogens have been proven to be the leading contributors to myopericarditis in the pediatric and adult populations. Despite the current comprehensive knowledge of myocardial injury in viral and post-viral myopericarditis, the cellular and molecular mechanisms of SARS-CoV-2-induced myopericarditis are poorly understood. This report presents a case of coronavirus (COVID-19) fulminant myopericarditis and acute respiratory distress syndrome (ARDS) in a middle-aged male patient: a 51-year-old man with a history of hypertension who arrived to the emergency department with a dry cough, fatigue, dyspnea, and a fever. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay confirmed a diagnosis of COVID-19 infection, resulting in the patient’s admission to the airborne isolation unit for clinical observation. When his condition began to deteriorate, the patient was transferred to the cardiac care unit after electrocardiography detected cardiac injury, demonstrating diffuse ST-segment elevation. Laboratory evaluations revealed elevated troponin T and BNP, with an echocardiogram indicating global left ventricular hypokinesia and a reduced ejection fraction. The patient was treated with hydroxychloroquine, azithromycin, dobutamine, remdesivir, and ventilatory support. This specific case highlights the severity and complications that may arise as a direct result of COVID-19 infection.


title: Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand

text: BACKGROUND: Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. A cross-sectional study was conducted in Thailand to assess rabies-related knowledge and practices among persons regularly exposed to bats and bat habitats. The objectives were to identify deficiencies in rabies awareness, describe the occurrence of bat exposures, and explore factors associated with transdermal bat exposures. METHODS: A survey was administered to a convenience sample of adult guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. The questionnaire elicited information on demographics, experience with bat exposures, and rabies knowledge. Participants were also asked to describe actions they would take in response to a bat bite as well as actions for a bite from a potentially rabid animal. Bivariate analysis was used to compare responses between groups and multivariable logistic regression was used to explore factors independently associated with being bitten or scratched by a bat. FINDINGS: Of 106 people interviewed, 11 (10%) identified bats as a potential source of rabies. A history of a bat bite or scratch was reported by 29 (27%), and 38 (36%) stated either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of rabies transmission (68% vs. 90%, p = 0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p = 0.003). Guano mining, bat hunting, and being in a bat cave or roost area more than 5 times a year were associated with history of a bat bite or scratch. CONCLUSIONS: These findings indicate the need for educational outreach to raise awareness of bat rabies, promote exposure prevention, and ensure appropriate health-seeking behaviors for bat-inflicted wounds, particularly among at-risk groups in Thailand.


title: A logistic growth model for COVID-19 proliferation: experiences from China and international implications in infectious diseases

text: Abstract Objective As the COVID-19 global pandemic continues its proliferation globally, this paper shares the findings and experiences of modelling the outbreak in China and its provinces and proposes implications for the study of infectious diseases and the COVID-19 pandemic in other nations. Methods An NLS (non-linear least square) method estimated the parameters of a differentiated logistic growth function of new COVID-19 cases in multiple regions in China and nations with a large amount of cases based on training data from Feb. 20 to Mar. 13. A restriction test was subsequently employed to test whether a designated parameter was identical among regions or countries. We conducted diagnosis of the residuals and also its goodness of fit with testing data from Mar. 13 to Apr. 18. Findings We find that the model fits time series data exceedingly well in China, its provinces, and two other nations, and we provide estimates of key parameters. We reject the null hypothesis that the growth rate of the outbreak is the same among ten selected provinces as well as between South Korea and Iran. We also find that the model does not provide reliable estimates in countries that are in the early stages of outbreak. We further find that the R 2 value be varied and misleading when compared among different curves of the same nonlinear model, as well as the existence of heteroskedasticity and positive serial correlation within residuals in some provinces and nations. Conclusion We believe that there is potential for our model to contribute to better public health policy combatting COVID-19 by providing a simple logistical framework for retrospectively analyzing the outbreak in regions that have already experienced maximal proliferation in cases. However, based upon our statistical findings, we outline certain pitfalls in modelling and their implications on results.


title: Amelioration of oxidative stress using N‐acetylcysteine in canine parvoviral enteritis

text: Previously, antioxidants have not been evaluated for treatment of parvoviral diarrhea in dogs. In this study, antioxidant potential of N‐acetylcysteine (NAC) in dogs infected with canine parvovirus with a nonblinded randomized clinical trial has been carried out. A total 18 parvo‐infected dogs were randomly divided into two groups: nine parvo‐infected dogs were treated with supportive treatment and nine parvo‐infected dogs were treated with NAC along with supportive treatment. Simultaneously, nine healthy dogs were kept as healthy control. In parvo‐infected dogs, marked hemoconcentration, leucopenia, neutropenia and oxidative stress were noticed compared to healthy dogs. The NAC treatment progressively improved the leukocyte, neutrophil, monocyte, and eosinophil counts over the time in parvovirus‐infected dogs compared to dogs that received only supportive treatment. In addition, NAC treatment significantly improved glutathione S‐transferase (GST) activity and decreased nitrite plus nitrate (NOx) and malondialdehyde (MDA) concentrations on day 3 and 5 compared to supportive treatment in parvo‐infected dogs. However, supportive treatment alone failed to ameliorate oxidative stress in the infected dogs till day 5. The results of this study suggest that NAC represents a potential additional treatment option that could be considered to improve the health condition and minimize the duration of hospitalization in case of canine parvoviral diarrhea.


title: Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen

text: BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI. METHODS: Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results. RESULTS: The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant. CONCLUSIONS: Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2118-6) contains supplementary material, which is available to authorized users.


title: Methods to infer transmission risk factors in complex outbreak data

text: Data collected during outbreaks are essential to better understand infectious disease transmission and design effective control strategies. But analysis of such data is challenging owing to the dependency between observations that is typically observed in an outbreak and to missing data. In this paper, we discuss strategies to tackle some of the ongoing challenges in the analysis of outbreak data. We present a relatively generic statistical model for the estimation of transmission risk factors, and discuss algorithms to estimate its parameters for different levels of missing data. We look at the problem of computational times for relatively large datasets and show how they can be reduced by appropriate use of discretization, sufficient statistics and some simple assumptions on the natural history of the disease. We also discuss approaches to integrate parametric model fitting and tree reconstruction methods in coherent statistical analyses. The methods are tested on both real and simulated datasets of large outbreaks in structured populations.


title: Coronavirus disease 2019: International public health considerations

text: On December 31, 2019, the Chinese government announced an outbreak of a novel coronavirus, recently named COVID‐19. During the following weeks the international medical community has witnessed with unprecedented coverage the public health response both domestically by the Chinese government, and on an international scale as cases have spread to dozens of countries. While much regarding the virus and the Chinese public health response is still unknown, national and public health institutions globally are preparing for a pandemic. As cases and spread of the virus grow, emergency and other front‐line providers may become more anxious about the possibility of encountering a potential case. This review describes the tenets of a public health response to an infectious outbreak by using recent historical examples and also by characterizing what is known about the ongoing response to the COVID‐19 outbreak. The intent of the review is to empower the practitioner to monitor and evaluate the local, national and global public health response to an emerging infectious disease.


title: Tracking the viruses that cause the Hajj cough

text: The first study to track viral infection over an entire pilgrimage to Mecca sheds light on the Hajj cough – and how the deadly MERS virus might spread


title: Salivary gland disease in the era of COVID‐19 pandemic

text: Coronavirus disease 2019 (COVID‐19) pandemic forced significant changes in current approach to outpatient evaluation of common otolaryngology complaints as hospitals around the world are trying to limit the spread of the virus and to preserve health care resources. These changes raise a lot of questions regarding patient triage and treatment decisions in clinical situations when it is unclear if the workup and management can be postponed. In this communication, we present our approach to evaluation and triage of new patients with complaints concerning for salivary gland disease.


title: 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate

text: Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.


title: Pandemic Preparedness: Developing Vaccines and Therapeutic Antibodies For COVID-19

text: Abstract The SARS-CoV-2 pandemic that causes COVID-19 respiratory syndrome has caused global public health and economic crises necessitating rapid development of vaccines and therapeutic countermeasures. The world-wide response to the COVID-19 pandemic has been unprecedented with government, academic and private partnerships working together to rapidly develop vaccine and antibody countermeasures. Many of the technologies being used are derived from prior government-academic partnerships for response to other emerging infections.


title: Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model

text: Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure–response relationships. The model was finally validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2–5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2–3: 500 mg BID, Days 4–5250 mg BID, CQ phosphate), and other vulnerable populations (e.g., renal and hepatic impairment and elderly patients, Days 1–5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.


title: Global measles elimination

text: Measles remains a leading vaccine-preventable cause of child mortality worldwide, particularly in sub-Saharan Africa where almost half of the estimated 454,000 measles deaths in 2004 occurred. However, great progress in measles control has been made in resource-poor countries through accelerated measles-control efforts. The global elimination of measles has been debated since measles vaccines were first licensed in the 1960's, and this debate is likely to be renewed if polio virus is eradicated. This review discusses the pathogenesis of measles and the likelihood of the worldwide elimination of this disease.


title: Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection

text: Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.


docid: faqjxxrl

title: Exploring global food system shocks, scenarios and outcomes

text: Globalised food supply chains are increasingly susceptible to systemic risks, with natural, social and economic shocks in one region potentially leading to price spikes and supply changes experienced at the global scale. When projections extrapolate from recent histories and adopt a ‘business as usual’ approach they risk failing to take account of shocks or unpredictable events that can have dramatic consequences for the status quo as seen with the global Covid-19 pandemic. This study used an explorative stakeholder process and shock centred narratives to discuss the potential impact of a diversity of shocks, examining system characteristics and trends that may amplify their impact. Through the development of scenarios, stakeholders revealed concerns about the stability of the food system and the social, economic and environmental consequence of food related shocks. Increasing connectivity served as a mechanism to heighten volatility and vulnerability within all scenarios, with reliance on singular crops and technologies (i.e. low diversity) throughout systems highlighted as another potential source of vulnerability. The growing role of social media in shaping attitudes and behaviours towards food, and the increasing role of automation emerged as contemporary areas of concern, which have thus far been little explored within the literature.


title: How to make predictions about future infectious disease risks

text: Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the ‘art of the possible’, which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for ‘good practice’ for the development and the use of predictive models.


title: Epidemiology and Immune Pathogenesis of Viral Sepsis

text: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment.


Chapter 8 The peritoneum


title: Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019 (COVID-19)

text: The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person-to-person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizol-based RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.


title: IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation

text: As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats.


title: Toward a resolution of the cost of equity conundrum in the lodging industry: a conceptual framework

text: The firm value estimate is derived from accounting and finance practices that focus on physical assets as opposed to intangible assets (Arthur Andersen Hospitality Leisure Executive Rep. 5 (1998) 2). The cost of equity estimation models used in firm valuation and capital investment decisions fall short of tapping important constructs to firm value, especially the intangible ones. The purpose of this study is to assess the present cost of equity capital determination models and provide a view of their relevancy for the lodging industry while simultaneously attempting to propose new options to meet the valuation and capital budgeting needs of the lodging industry.


title: Public health interventions for epidemics: implications for multiple infection waves

text: BACKGROUND: Epidemics with multiple infection waves have been documented for some human diseases, most notably during past influenza pandemics. While pathogen evolution, co-infection, and behavioural changes have been proposed as possible mechanisms for the occurrence of subsequent outbreaks, the effect of public health interventions remains undetermined. METHODS: We develop mean-field and stochastic epidemiological models for disease transmission, and perform simulations to show how control measures, such as drug treatment and isolation of ill individuals, can influence the epidemic profile and generate sequences of infection waves with different characteristics. RESULTS: We demonstrate the impact of parameters representing the effectiveness and adverse consequences of intervention measures, such as treatment and emergence of drug resistance, on the spread of a pathogen in the population. If pathogen resistant strains evolve under drug pressure, multiple outbreaks are possible with variability in their characteristics, magnitude, and timing. In this context, the level of drug use and isolation capacity play an important role in the occurrence of subsequent outbreaks. Our simulations for influenza infection as a case study indicate that the intensive use of these interventions during the early stages of the epidemic could delay the spread of disease, but it may also result in later infection waves with possibly larger magnitudes. CONCLUSIONS: The findings highlight the importance of intervention parameters in the process of public health decision-making, and in evaluating control measures when facing substantial uncertainty regarding the epidemiological characteristics of an emerging infectious pathogen. Critical factors that influence population health including evolutionary responses of the pathogen under the pressure of different intervention measures during an epidemic should be considered for the design of effective strategies that address short-term targets compatible with long-term disease outcomes.


title: Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms

text: The prevalence of human rhino‐, entero‐, and coronaviruses was investigated by RT‐PCR in nasopharyngeal aspirates from 107 children without concurrent respiratory symptoms. The children were admitted to the hospital for elective surgery. The parents filled a questionnaire about the occurrence of respiratory symptoms four weeks before and two weeks after the surgery. The rate of viral detection was 45% in children with related past or recent respiratory infection whereas 20% of the samples taken from children without any related past or recent respiratory infections were positive for picornavirus RNA, P = 0.008. Thirty‐one (29%) of the nasopharyngeal aspirates were positive for viral RNA, 18% for rhinovirus, and 11% for enterovirus RNA. Coronavirus RNA was not found in any of the children. Fifty‐five percent of the children with virus‐positive samples had an infection‐related diagnosis. In addition, 81% of the children with virus‐positive samples had had previously respiratory symptoms or there were concurrent respiratory symptoms in other family members. Only four of the 31 virus‐positive samples were from children without infection‐related diagnosis or recent past (or immediate future) respiratory symptoms. J. Med. Virol. 66:417‐420, 2002. © 2002 Wiley‐Liss, Inc.


title: Is the brain a reservoir organ for SARS2‐CoV2?

text: Paniz-Mondolfi et al have published an interesting necropsy case of a patient with Parkinson's disease and SARS2-CoV infection in which the virus is found in neurons of the frontal lobe. The authors analyze these findings about the possibility that the brain is a reservoir of the virus as has been observed with other CoVs. This article is protected by copyright. All rights reserved.


Addendum to: Eruption as a clinical manifestation of COVID-19: Photographs of a patient


Mental Health Status of the General Population in Japan during the COVID‐19 Pandemic


title: China and SARS: could do better

text: Has the world's most populous nation learnt the lessons of last year's SARS outbreak? Only partially, it seems.


title: Analysis of SARS-CoV-2 Screening Clinic (Including Drive-Through System) Data at a Single University Hospital in South Korea from 27 January 2020 to 31 March 2020 during the COVID-19 Outbreak.

text: In this study, we evaluated the efficiency of a drive-through (DT) screening system for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by comparing it with a conventional screening system. We reviewed and analyzed the SARS-CoV-2 screening data obtained at our university hospital. We compared the number of tests for SARS-CoV-2 (using real-time polymerase chain reaction) performed using two different specimen collection systems-DT and conventional-during the coronavirus disease 2019 (COVID-19) outbreak in Daegu. Based on the results, the DT screening system collected 5.8 times more specimens for testing than the conventional screening system. From January 27 to 31 March 2020, 6211 individuals were screened for SARS-CoV-2 infection using either the DT or conventional system. In total, 217 individuals tested positive for SARS-CoV-2 (positive rate: 3.50%). Of the 6211 individuals, 3368 were symptomatic or had a history of contact with COVID-19 patients, and 142 of them tested positive for SARS-CoV-2 (positive rate: 4.22%). Further, 2843 individuals were asymptomatic and had no history of contact with COVID-19 patients, and 75 of them tested positive for SARS-CoV-2 (positive rate: 2.64%). In conclusion, the DT system allowed clinicians to collect specimens for SARS-CoV-2 screening more efficiently than the conventional system. Furthermore, as there might be several COVID-19 patients who remain asymptomatic, expanding the screening test to asymptomatic individuals would be necessary.


title: Laboratory characteristics of pregnant compared to non-pregnant women infected with SARS-CoV-2

text: KEY MESSAGE: Laboratory characteristics of SARS-CoV-2 infection did not differ between pregnant and non-pregnant women. A trend of lower lymphocyte count was observed in the pregnant women group PURPOSE: Laboratory abnormalities, which characterize SARS-CoV-2 infection have been identified, nevertheless, data concerning laboratory characteristics of pregnant women with SARS-CoV-2 are limited. The aim of this study is to evaluate the laboratory characteristics of pregnant compared to non-pregnant women with SARS-CoV-2 infection. METHODS: A retrospective cohort study of all pregnant women with SARS-CoV-2 who were examined at the obstetric emergency room in a tertiary medical center between March and April 2020. Patients were compared with non-pregnant women with SARS-CoV-2 matched by age, who were examined at the general emergency room during the study period. All patients were confirmed for SARS-CoV-2 on admission. Clinical characteristics and laboratory results were compared between the groups. RESULTS: Study group included 11 pregnant women with SARS-CoV-2, who were compared to 25 non-pregnant controls. Respiratory complaints were the most frequent reason for emergency room visit, and were reported in 54.5% and 80.0% of the pregnant and control groups, respectively (p = 0.12). White blood cells, hemoglobin, platelets, and liver enzymes counts were within the normal range in both groups. Lyphocytopenia was observed in 45.5% and 32% of the pregnant and control groups, respectively (p = 0.44). The relative lymphocyte count to WBC was significantly reduced in the pregnant group compared to the controls [13.6% (4.5–19.3) vs. 26.5% (15.7–29.9); p = 0.003]. C-reactive protein [20(5–41) vs. 14 (2–52) mg/dL; p = 0.81] levels were elevated in both groups but without significant difference between them. CONCLUSION: Laboratory characteristics of SARS-CoV-2 infection did not differ between pregnant and non-pregnant women, although a trend of lower lymphocyte count was observed in the pregnant women group.


title: The virulence of mouse hepatitis virus strain A59 is not dependent on efficient spike protein cleavage and cell-to-cell fusion

text: The cleavage and fusion properties of recombinant murine hepatitis viruses (MHV) were examined to assess the role of the cleavage signal in determining the extent of S protein cleavage, and the correlation between cleavage and induction of cell-to-cell fusion. Targeted recombination was used to introduce amino acid substitutions into the cleavage signal of the fusion glycoprotein (spike or S protein) of MHV strain A59. The recombinants were then used to address the question of the importance of S protein cleavage and viral-mediated cell-to-cell fusion on pathogenicity. Our data indicate that cleavage of spike is not solely determined by the amino acid sequence at the cleavage site, but may also depend on sequences removed from the cleavage site. In addition, efficient cell-to-cell fusion is not necessary for virulence.


title: EWI‐2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry

text: CD81 is a major receptor for Hepatitis C Virus (HCV). It belongs to the tetraspanin family whose members form dynamic clusters with numerous partner proteins and with one another, forming tetraspanin‐enriched areas in the plasma membrane. In our study, we combined single‐molecule microscopy and biochemistry experiments to investigate the clustering and membrane behaviour of CD81 in the context of cells expressing EWI‐2wint, a natural inhibitor of HCV entry. Interestingly, we found that EWI‐2wint reduces the global diffusion of CD81 molecules due to a decrease of the diffusion rate of mobile CD81molecules and an increase in the proportion of confined molecules. Indeed, we demonstrated that EWI‐2wint promotes CD81 clustering and confinement in CD81‐enriched areas. In addition, we showed that EWI‐2wint influences the colocalization of CD81 with Claudin‐1 – a co‐receptor required for HCV entry. Together, our results indicate that a change in membrane partitioning of CD81 occurs in the presence of EWI‐2wint. This study gives new insights on the mechanism by which HCV enters into its target cells, namely by exploiting the dynamic properties of CD81.