title: Chapter 6 Virus population dynamics examined with experimental model systems

text: Abstract Experimental evolution permits exploring the effect of controlled environmental variables in virus evolution. Several designs in cell culture and in vivo have established basic concepts that can assist in the interpretation of evolutionary events in the field. Important information has come from cytolytic and persistent infections in cell culture that have unveiled the power of virus-cell coevolution in virus and cell diversification. Equally informative are comparisons of the response of viral populations when subjected to different passage régimens. In particular, plaque-to-plaque transfers in cell culture have revealed unusual genotypes and phenotypes that populate minority layers of viral quasispecies. Some of these viruses display properties that contradict features established in virology textbooks. Several hypotheses and principles of population genetics have found experimental confirmation in experimental designs with viruses. The possibilities of using experimental evolution to understand virus behavior are still largely unexploited.


title: Identification of Influential users on Twitter: A Novel Weighted Correlated Influence Measure for Covid-19

text: In the era of advanced mobile technology, freedom of expression over social media has become prevalent among online users. This generates a huge amount of communication that eventually forms a ground for extensive research and analysis. The social network analysis allows identifying the influential people in society over microblogging platforms. Twitter, being an evolving social media platform, has become increasingly vital for online dialogues, trends, and content virality. Applications of discovering influential users over Twitter are manifold. It includes viral marketing, brand analysis, news dissemination, health awareness spreading, propagating political movement, and opinion leaders for empowering governance. In our research, we have proposed a sustainable approach, namely Weighted Correlated Influence (WCI), which incorporates the relative impact of timeline-based and trend-specific features of online users. Our methodology considers merging the profile activity and underlying network topology to designate online users with an influence score, which represents the combined effect. To quantify the performance of our proposed method, the Twitter trend #CoronavirusPandemic is used. Also, the results are validated for another social media trend. The experimental outcomes depict enhanced performance of proposed WCI over existing methods that are based on precision, recall, and F1-measure for validation.


A special edition of the Journal of Visceral Surgery on Covid-19: what problems, dangers and solutions have been identified?


title: Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy?()

text: BACKGROUND AND OBJETIVE: On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy. PATIENTS AND METHODS: Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy. RESULTS: There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid. CONCLUSIONS: It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.


title: CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES‐I statement): an extension of the STROBE statement

text: BACKGROUND: Population‐based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting. OBJECTIVE: The objective of the CONSISE ROSES ‐I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results. METHODS: The ROSES‐I statement was developed as an expert consensus of the CONSISE epidemiology and laboratory working groups. The recommendations are presented in the familiar format of a reporting guideline. Because seroepidemiologic studies are a specific type of observational epidemiology study, the ROSES‐I statement is built upon the STROBE guidelines. As such, the ROSES‐I statement should be seen as an extension of the STROBE guidelines. RESULTS: The ROSES ‐I statement presents 42 items that can be used as a checklist of the information that should be included in the results of published seroepidemiologic studies, and which can also serve as a guide to the items that need to be considered during study design and implementation. CONCLUSIONS: We hope that the ROSES‐I statement will contribute to improving the quality of reporting of seroepidemiologic studies.


Abstract 42. Metabolic alterations of HSV-1-infected neurons: studies using the PC12 cell as a model system


title: Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design

text: In December 2019, the first cases of a novel coronavirus infection causing COVID-19 were diagnosed in Wuhan, China. Viral Papain-Like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library containing natural and a wide variety of nonproteinogenic amino acids and performed comprehensive activity profiling of SARS-CoV-2-PLpro. On the scaffold of best hits from positional scanning we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro variants versus other proteases. We determined crystal structures of two of these inhibitors (VIR250 and VIR251) in complex with SARS-CoV-2-PLpro which reveals their inhibitory mechanisms and provides a structural basis for the observed substrate specificity profiles. Lastly, we demonstrate that SARS-CoV-2-PLpro harbors deISGylating activities similar to SARS-CoV-1-PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Altogether this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repositioning.


title: Korean Society for Laboratory Medicine Practice Guidelines for the Molecular Diagnosis of Middle East Respiratory Syndrome During an Outbreak in Korea in 2015

text: For two months between May and July 2015, a nationwide outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) occurred in Korea. On June 3, 2015, the Korean Society for Laboratory Medicine (KSLM) launched a MERS-CoV Laboratory Response Task Force (LR-TF) to facilitate clinical laboratories to set up the diagnosis of MERS-CoV infection. Based on the WHO interim recommendations, the Centers for Disease Control and Prevention of United States guidelines for MERS-CoV laboratory testing, and other available resources, the KSLM MERS-CoV LR-TF provided the first version of the laboratory practice guidelines for the molecular diagnosis of MERS-CoV to the clinical laboratories on June 12, 2015. The guidelines described here are an updated version that includes case definition, indications for testing, specimen type and protocols for specimen collection, specimen packing and transport, specimen handling and nucleic acid extraction, molecular detection of MERS-CoV, interpretation of results and reporting, and laboratory safety. The KSLM guidelines mainly focus on the molecular diagnosis of MERS-CoV, reflecting the unique situation in Korea and the state of knowledge at the time of publication.


title: Online Databases and Non-coding RNAs in Cardiovascular Diseases

text: Cardiovascular disease is characterized by its highest morbidity and mortality. One of the main pathological basis of this disease is the dysregulation of gene expression. Non-coding RNA (ncRNA) is a kind of functional RNA, which is transcript from DNA but not translated into proteins. More and more studies have established the important roles of ncRNAs, including transcription, RNA maturation, translation, protein degradation, and their involvement in the pathogenesis of diseases such as cancer and cardiovascular diseases. This chapter will focus on the biological functions of ncRNAs and their advances in cardiovascular disease. With the development of sequencing and computer technology, more and more databases can be easily obtained on the internet. In another part of this chapter, we will summarize some commonly used non-coding RNA databases, which can be easily and quickly used for relevant research.


title: Altitude impact on the chemical profile and biological activities of Satureja thymbra L. essential oil

text: BACKGROUND: Several agricultural or environmental factors affect plants’ chemical and pharmacological properties. METHODS: In this study, the essential oil of Libyan Satureja thymbra was isolated from plants collected during two successive years at two different altitudes; Wasita (WEO) and Safsaf (SEO), 156 and 661 m above sea level, respectively. RESULTS: GC/MS allowed the identification of 21 and 23 compounds, respectively. Thymol prevailed in WEO (26.69%), while carvacrol prevailed in SEO (14.30%). Antimicrobial activity was tested by agar-well diffusion method, and MIC/MLC values were determined by broth dilution method. Values of MIC/MLC were 0.125/0.25 μg/ml for SEO against S. aureus, P. mirabilis and K. pneumonia and for WEO against B. subtilus. It was observed that plants growing at lower altitude in Wasita locality had better antifungal activity, while those growing at higher altitude at Safsaf locality had better antibacterial activity. Both essential oils had a better anthelmintic activity than the standard piperazine citrate against a tested earthworm. However, SEO oil had a significantly higher anthelmintic activity than WEO. Cytotoxicity of the oils tested using SRB assay on human breast cancer (MCF-7) and colon cancer cell lines (HCT-116) showed better activity for SEO, especially against HCT-116 with IC(50) 2.45 ± 0.21 μg/ml. CONCLUSIONS: Thus, altitude is an important factor that should be considered as it affected the yield, composition and biology of the plant extracts.


title: Community-Acquired Pneumonia in HIV-Infected Individuals

text: Community-acquired pneumonia continues to be an important complication of HIV infection. Rates of pneumonia decrease with the use of antiretroviral therapy but continue to be higher than in HIV uninfected individuals. Risk factors for pneumonia include low blood CD4+ count, unsuppressed plasma HIV load, smoking, injection drug use and renal impairment. Immunization against Streptococcus pneumoniae and smoking cessation can reduce this risk. It is unclear whether newly reported viral respiratory pathogens (such as the Middle East respiratory syndrome coronavirus, will be more of a problem in HIV-infected individuals than the general population.


Corrigendum to “World Health Organization declares Global Emergency: A review of the 2019 Novel Coronavirus (COVID-19)” [Int. J. Surg. 76 (2020) 71–76]


title: A scoring system for management of acute pharyngo-tonsillitis in adults

text: Abstract Objectives The aim of this study was to develop and evaluate a scoring system for the management of acute pharyngo-tonsillitis. Methods We conducted a prospective study between May 2004 and June 2005. Patients with acute pharyngo-tonsillitis were evaluated for causative pathogens and were assessed clinical symptoms and pharyngo-tonsillar finding by a clinical scoring system. Results A total 214 adult patients were enrolled in this study. Streptococcus pyogenes were identified at 13.6%. Thirty-one viruses were also identified by PCR. They were adenovirus (4.8%), influenza virus (1.0%), RS virus (6.3%), and human metapneumovirus (2.9%). Numbers of total white blood cells and levels of C-reactive protein showed a significant positive correlation with clinical scores (p <0.001) and were also higher in cases with S. pyogenes. The clinical scores rapidly improved after the antimicrobial treatments in moderate cases and severe cases. Conclusion The current study strongly suggested that the clinical scoring system reflected disease severity well and would be very useful for evaluating clinical course and decision making for the antimicrobial treatment of acute pharyngo-tonisllitis.


title: Moment closure of infectious diseases model on heterogeneous metapopulation network

text: The global transmission of infectious diseases poses huge threats to human. Traditional heterogeneous mean-field models on metapopulation networks ignore the heterogeneity of individuals who are in different disease states in subpopulations with the same degree, resulting in inaccuracy in predicting the spread of disease. In this paper, we take heterogeneity of susceptible and infectious individuals in subpopulations with the same degree into account, and propose a deterministic unclosed general model according to Markov process on metapopulation networks to curve the global transmission of diseases precisely. Then we make the general model closed by putting forward two common assumptions: a two-dimensional constant distribution and a two-dimensional log-normal distribution, where the former is equivalent to the heterogeneous mean-field model, and the latter is a system of weighted ordinary differential equations. Further we make a stability analysis for two closed models and illustrate the results by numerical simulations. Next, we conduct a series of numerical simulations and stochastic simulations. Results indicate that our general model extends and optimizes the mean-field model. Finally, we investigate the impacts of total mobility rate on disease transmission and find that timely and comprehensive travel restriction in the early stage is an effective prevention and control of infectious diseases.


title: Clinical Management of Patients with Ebola Virus Disease in High-Resource Settings

text: Like most viral illnesses in humans, supportive care of the patient is the mainstay of clinical care for patients with Ebola virus disease (EVD). The goal is to maintain and sustain the patient until a specific immune response develops and clears the viral infection. Clearly, antiviral therapy may eventually help speed recovery, but supportive care will likely always be the centerpiece of care of the patient with EVD. While terrible in terms of human suffering and loss, the EVD outbreak of 2014–2016 provided an unheralded opportunity to advance our understanding in the care of patients (WHO 2016). Regardless of the care setting, resource-rich or resource-constrained, it is beneficial to have an established team of care providers. This team should consist of nurses and physicians who are familiar with clinical care of patients with EVD and have demonstrated competency using necessary personal protective equipment (PPE). Consideration should be given to having several physician specialties on the team, including critical care, infectious diseases, and anesthesiology. Additional individuals in other medical specialties should be identified in case needed during the course of caring for a patient. The National Ebola Training and Education Center (NETEC) has detailed guidance on preparations for developing a high-containment unit and care team (NETEC 2016).


MORTALITY FROM COVID-19 INCREASES WITH UNSATURATED FAT, AND MAY BE REDUCED BY EARLY CALCIUM AND ALBUMIN SUPPLEMENTATION


title: Respiratory viruses transmission from children to adults within a household

text: BACKGROUND: The aim of this study was to examine the rate of transmission of influenza and other respiratory viruses from children attending an Emergency Department to their family members in the household using active surveillance. METHODS: A prospective hospital-based study was conducted over three consecutive winters (2006–2008) in children aged <1–15 years presenting with influenza-like illness (ILI). 168 children with ILI and their healthy families were recruited over three winter seasons. RESULTS: Respiratory viruses were detected in 101 (60.8%) children with ILI; in 91/166 (54.8%) a single pathogen was detected, and in the remaining 10 children more than one virus was detected concurrently. Influenza was the most common virus detected (34/101), followed by rhinoviruses (22/101) and adenoviruses (14/101). Of influenza viruses, 21/34 were influenza A and 13/34 influenza B. Meeting the clinical definition of ILI did not differentiate between influenza and other viruses. Clinical ILI developed within one week of follow up in 12% (26/205) of the family members who were swabbed. Viral pathogens were detected in 42.3% (11/26) of the symptomatic family members. In 6/11 cases the same virus was detected in the adult and child. The lower estimate of the household risk of transmission of respiratory viruses, based on concordant proven infection in both child and adult, from a single sick child to adult household contacts is therefore 3% per week. CONCLUSION: This study provides quantitative, prospective data on rates of household transmission of infection from children to adults.


title: Does China’s high-speed rail development lead to regional disparities? A network perspective

text: This research examines whether cities are getting more equally accessible and connected via high-speed rail (HSR) in China over the period from 2010 to 2015. Existing studies mainly use network centralities to describe the spatial pattern of HSR network without measuring the spatial disparity of these centralities, and most of them rely on the infrastructure network and thus fail to incorporate HSR service quality in the centrality measures. Using HSR timetable data, we incorporate both scheduled travel time and daily frequency of each origin-destination city pair into three centrality measures and further quantify their inequalities using Theil’s T index. We find that as the HSR network expands, cities appear to be more equal in terms of accessibility, but their disparities in connectivity and transitivity depend on the dimensions of comparison. In general, although the difference between economic regions or between megalopolises has reduced, small/medium-sized cities not belonging to any major city cluster are further lagged behind in HSR development. The difference between core and non-core cities in the same megalopolises has decreased despite that non-core cities are increasingly relying on core cities to access other regions.


title: Exercising in Times of Lockdown: An Analysis of the Impact of COVID-19 on Levels and Patterns of Exercise among Adults in Belgium

text: Countries all over the world implemented lockdowns to counteract COVID-19. These lockdowns heavily limited people’s exercise possibilities. At the same time, experts advocated to remain physically active to prevent future health problems. Based on an online survey, this study examines adults’ exercise levels and patterns during the COVID-19 lockdown in Belgium. Ordinal logistic regression analyses of 13,515 valid and population-weighted responses indicate a general increase in exercise frequencies, as well as in sedentary behavior. Except for people aged 55+, previously low active adults self-reported to exercise more during the lockdown. Among the people who were already high active before COVID-19, those above 55 years old, those with low education, those used to exercise with friends or in a sport club, and those who were not using online tools to exercise, self-reported to exercise less during the lockdown. Having less time, sitting more, and missing the familiar way and competitive element of exercising were the main reasons for a self-reported exercise reduction. Given the health risks associated with physical inactivity, results imply that governments should consider how those who were not reached can be encouraged to exercise during a lockdown. After all, additional COVID-19 lockdowns might be implemented in the future.


title: CD81 Receptor Regions outside the Large Extracellular Loop Determine Hepatitis C Virus Entry into Hepatoma Cells

text: Hepatitis C virus (HCV) enters human hepatocytes using four essential entry factors, one of which is human CD81 (hCD81). The tetraspanin hCD81 contains a large extracellular loop (LEL), which interacts with the E2 glycoprotein of HCV. The role of the non-LEL regions of hCD81 (intracellular tails, four transmembrane domains, small extracellular loop and intracellular loop) is poorly understood. Here, we studied the contribution of these domains to HCV susceptibility of hepatoma cells by generating chimeras of related tetraspanins with the hCD81 LEL. Our results show that non-LEL regions in addition to the LEL determine susceptibility of cells to HCV. While closely related tetraspanins (X. tropicalis CD81 and D. rerio CD81) functionally complement hCD81 non-LEL regions, distantly related tetraspanins (C. elegans TSP9 amd D. melanogaster TSP96F) do not and tetraspanins with intermediate homology (hCD9) show an intermediate phenotype. Tetraspanin homology and susceptibility to HCV correlate positively. For some chimeras, infectivity correlates with surface expression. In contrast, the hCD9 chimera is fully surface expressed, binds HCV E2 glycoprotein but is impaired in HCV receptor function. We demonstrate that a cholesterol-coordinating glutamate residue in CD81, which hCD9 lacks, promotes HCV infection. This work highlights the hCD81 non-LEL regions as additional HCV susceptibility-determining factors.


title: Custom-made vaccines at speed

text: The concept of reverse genetics has enabled researchers to construct an experimental vaccine against a potential pandemic influenza strain in less than a month.


title: Enteropathogen co-infection in UK cats with diarrhoea

text: BACKGROUND: Individual enteropathogen infections in healthy and clinically ill cats are well described, but prevalence and patterns of enteropathogen co-infection have only been reported on a limited basis. We studied enteropathogen co-infection in diarrhoeic UK cats using results of a real time PCR assay for 8 enteropathogenic species; feline coronavirus (Co), feline panleukopenia virus (Pa), Clostridium perfringens (Cl), Salmonella enterica (Sa), Giardia spp. (Gi), Tritrichomonas foetus (Tr), Cryptosporidium spp. (Cr), and Toxoplasma gondii (To). Age, gender, breed and history were recorded. PCR panels from 1088 diarrhoeic cats were available for analysis. RESULTS: Overall enteropathogen prevalence was 56.9% (Co), 22.1% (Pa), 56.6% (Cl), 0.8% (Sa), 20.6% (Gi), 18.8% (Tr), 24.4% (Cr) and 1.0% (To). Prevalence of Co, Gi and Tr was higher in pedigree cats compared to non-pedigree cats (DSH) and prevalence decreased with increasing age for Co, Pa, Gi, Cr and Tr. Co-infection was common: ≥2 enteropathogens were detected in 62.5% of cats, and 13.3% of cats had ≥4 enteropathogens. Mean ( [Formula: see text]) enteropathogen co-infection 2.01 (±1.3 SD), was significantly higher in pedigree cats ( [Formula: see text] =2.51) compared to DSH ( [Formula: see text] =1.68) and decreased with age ( [Formula: see text] =2.64 <6 months, [Formula: see text] =1.68 for >1 yr). More cats were negative for all 8 enteropathogens tested (12.7%) than expected. When exact combinations of co-infection were examined, Tr tended to be found in combinations with Co, Cl, and Gi. CONCLUSIONS: Multiple infections should be considered the most likely result of faecal testing in cats, and case management needs to take this into account. In contrast, the relatively high percentage of cats negative for all 8 enteropathogens tested could indicate an innate resistance to infection. Alternatively it could indicate a lack of exposure to these 8 enteropathogens or the presence of other enteropathogens not assessed by this assay.


title: Emergency Response to COVID-19 in Canada: Platform Development and Implementation for eHealth in Crisis Management

text: BACKGROUND: Public health emergencies like epidemics put enormous pressure on health care systems while revealing deep structural and functional problems in the organization of care. The current coronavirus disease (COVID-19) pandemic illustrates this at a global level. The sudden increased demand on delivery systems puts unique pressures on pre-established care pathways. These extraordinary times require efficient tools for smart governance and resource allocation. OBJECTIVE: The aim of this study is to develop an innovative web-based solution addressing the seemingly insurmountable challenges of triaging, monitoring, and delivering nonhospital services unleashed by the COVID-19 pandemic. METHODS: An adaptable crisis management digital platform was envisioned and designed with the goal of improving the system’s response on the basis of the literature; an existing shared health record platform; and discussions between health care providers, decision makers, academia, and the private sector in response to the COVID 19 epidemic. RESULTS: The Crisis Management Platform was developed and offered to health authorities in Ontario on a nonprofit basis. It has the capability to dramatically streamline patient intake, triage, monitoring, referral, and delivery of nonhospital services. It decentralizes the provision of services (by moving them online) and centralizes data gathering and analysis, maximizing the use of existing human resources, facilitating evidence-based decision making, and minimizing the risk to both users and providers. It has unlimited scale-up possibilities (only constrained by human health risk resource availability) with minimal marginal cost. Similar web-based solutions have the potential to fill an urgent gap in resource allocation, becoming a unique asset for health systems governance and management during critical times. They highlight the potential effectiveness of web-based solutions if built on an outcome-driven architecture. CONCLUSIONS: Data and web-based approaches in response to a public health crisis are key to evidence-driven oversight and management of public health emergencies.


title: Tailoring of the ongoing water, sanitation and hygiene interventions for prevention and control of COVID-19

text: Water, sanitation, and hygiene (WASH) interventions remain to be important in the prevention of further spread of coronavirus disease-2019 (COVID-19). Basic hygiene interventions such as handwashing with water and soap (HWWS) when applied consistently will deactivate and remove the virus particles from the hands. Realizing the efforts that have been made by countries world over in controlling the COVID-19, this letter seeks to discuss how the available WASH services can be used in the fight against further spread of COVID-19. The letter highlights the challenges being faced by the current WASH services in middle- and low-income countries and suggests measures that can be employed to strengthen the WASH services in this period of the COVID-19 pandemic.


title: Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity

text: Methyl-2-arylidene hydrazine-carbodithioate has not been of particular interest to researchers even though its metal complexes are extensively reported on due to their biological activity. This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC(50) value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. They were also most inhibitory to human embryonic lung (HEL) fibroblast proliferation (5.3 μM, 17 μM, and 2.6 μM). Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation.


The Cost Effectiveness of Stockpiling Drugs, Vaccines and Other Health Resources for Pandemic Preparedness


title: Environmental Impact: Concept, Consequences, Measurement ☆

text: Abstract Environments on Earth are always changing, and living systems evolve within them. For most of their history, human beings did the same. But in the last two centuries, humans have become the planet’s dominant species, changing and often degrading Earth’s environments and living systems, including human cultures, in unprecedented ways. Contemporary worldviews that have severed ancient connections between people and the environments that shaped us – plus our consumption and population growth – deepened this degradation. Understanding, measuring, and managing today’s human environmental impacts – the most important consequence of which is the impoverishment of living systems – is humanity’s greatest challenge for the 21st century.


title: Redecoration of apartments promotes obstructive bronchitis in atopy risk infants – Results of the LARS study

text: Abstract Findings by other authors indicate that exposure to chemical emissions from indoor paint is related to asthma symptoms in adults. In their first years of life children are receptive to obstructive airway diseases. The aim of this study was to investigate the influence of redecoration of the apartment on airway symptoms in infants during the first two years of life. The Leipzig Allergy Risk Children Study (LARS) is a birth cohort study with the following inclusion criteria: double positive family atopy anamnesis, cord blood IgE>0.9 kU/l, or low birth weight between 1500 – 2500 g. Within the context of LARS, 186 parents of risk children completed a questionnaire on the respiratory symptoms of their children and the redecoration of their apartment at the end of the first and second year of life. A total 22% of the children suffered from obstructive bronchitis once or more during their first year, and 11% experienced this condition during their second year of life. Redecoration of the apartment had a significant influence on the appearance of obstructive bronchitis in the first (OR 4.1 95%CI 1.4 – 11.9) and in the second year of life (OR 4.2 95%CI 1.4 – 12.9). (The OR are adjusted for cord blood-IgE >0.9 kU/l, birth weight ≤2500 g, male sex and double positive parental atopy anamnesis, dampness, smoking or pet in the apartment). Simultaneous contamination from redecoration activities and additional exposures such as smoking, a pet or dampness in the apartment increased the risk for obstructive bronchitis in the first year (OR 9.1; 95% CI 2.3 – 34.8) as well as in the second year (OR 5.1; 95%CI 1.6 – 15.6). Our data suggest that redecoration of the apartment is associated with the development of acute inflammations, but not with a chronic influence on the airways in atopy risk infants. At an exposure to more than one environmental factor, pronounced effects were seen.


title: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients

text: BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R(2) = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t = −2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


title: Chapter 17 Parasitic Diseases

text: Abstract Captive marmosets, whether in zoos or biomedical research facilities, may become infected or infested with a variety of internal or external parasites. Modern animal housing and husbandry practices have greatly reduced the prevalence of parasitism, particularly for those parasites requiring an intermediate host. In this chapter, the author discusses selected parasitic diseases of captive marmosets. This chapter is organized phylogenetically. No attempt is made to cover all of the internal and external parasites historically reported, no matter how infrequently. Similarly, no attempt is made to cover parasites infecting or infesting other New World primates and thus potentially found in or on marmosets. The author has included those parasitisms most likely to be observed in modern animal facilities.


title: Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV

text: [Image: see text] The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25 000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC(50) of 6 μM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC(50) of 11 μM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3).


title: Global prediction of unreported SARS-CoV2 infection from observed COVID-19 cases

text: Summary: Estimation of infectiousness and fatality of the SARS-CoV-2 virus in the COVID-19 global pandemic is complicated by ascertainment bias resulting from incomplete and non-representative samples of infected individuals. We developed a strategy for overcoming this bias to obtain more plausible estimates of the true values of key epidemiological variables. We fit mechanistic Bayesian latent-variable SIR models to confirmed COVID-19 cases, deaths, and recoveries, for all regions (countries and US states) independently. Bayesian averaging over models, we find that the raw infection incidence rate underestimates the true rate by a factor, the case ascertainment ratio CARt that depends upon region, and show how CARt changes over time. At the regional onset of COVID-19, the predicted global median for each case confirmed was 13 infections unreported (CARt = 0.07 C.I. (0.02, 0.4)). As the infection spread, the median CARt rose to 9 unreported cases for every one diagnosed as of April 15, 2020 (CARt = 0.1 C.I. (0.02, 0.5)). We also estimate that the median global initial reproduction number R0 is 3.3 (C.I (1.5, 8.3)) and the total infection fatality rate near the onset is 0.17% (C.I. (0.05%, 0.9%)). However the time-dependent reproduction number Rt and infection fatality rate as of April 15 were 1.2 (C.I. (0.6, 2.5)) and 0.8% (C.I. (0.2%,4%)), respectively. We find that there is great variability between country- and state-level values. Our estimates are consistent with recent serological estimates of cumulative infections for the state of New York, but inconsistent with claims that very large fractions of the population have already been infected in most other regions. For most regions, our estimates imply a great deal of uncertainty about the current state and trajectory of the epidemic.


title: Battle Buddies: Rapid Deployment of a Psychological Resilience Intervention for Health Care Workers During the Coronavirus Disease 2019 Pandemic

text: The outbreak of the coronavirus disease 2019 (COVID-19) and its rapid global spread have created unprecedented challenges to health care systems. Significant and sustained efforts have focused on mobilization of personal protective equipment, intensive care beds, and medical equipment, while substantially less attention has focused on preserving the psychological health of the medical workforce tasked with addressing the challenges of the pandemic. And yet, similar to battlefield conditions, health care workers are being confronted with ongoing uncertainty about resources, capacities, and risks; as well as exposure to suffering, death, and threats to their own safety. These conditions are engendering high levels of fear and anxiety in the shortterm, and place individuals at risk for persistent stressexposure syndromes, subclinical mental health symptoms, and professional burnout in the longterm. Given the potentially wide-ranging mental health impact of COVID-19, protecting health care workers from adverse psychological effects of the pandemic is critical. Therefore, we present an overview of the potential psychological stress responses to the COVID-19 crisis in medical providers and describe preemptive resilience-promoting strategies at the organizational and personal level. We then describe a rapidly deployable Psychological Resilience Intervention founded on a peersupport model (Battle Buddies) developed by the United States Army. This intervention—the product of a multidisciplinary collaboration between the Departments of Anesthesiology and Psychiatry & Behavioral Sciences at the University of Minnesota Medical Center—also incorporates evidence-informed “stress inoculation” methods developed for managing psychological stress exposure in providers deployed to disasters. Our multilevel, resource-efficient, and scalable approach places 2 key tools directly in the hands of providers: (1) apeersupport Battle Buddy; and (2) adesignated mental health consultant who can facilitate training in stress inoculation methods, provide additional support, or coordinate referral for external professional consultation. In parallel, we have instituted a voluntary research data-collection component that will enable us to evaluate the intervention’s effectiveness while also identifying the most salient resilience factors for future iterations. It is our hope that these elements will provide guidance to other organizations seeking to protect the well-being of their medical workforce during the pandemic. Given the remarkable adaptability of human beings, we believe that, by promoting resilience, our diverse health care workforce can emerge from this monumental challenge with new skills, closer relationships, and greater confidence in the power of community.


title: Experimental and numerical study on particle distribution in a two-zone chamber

text: Abstract Better understanding of aerosol dynamics is an important step for improving personal exposure assessments in indoor environments. Although the limitation of the assumptions in a well-mixed model is well known, there has been very little research reported in the published literature on the discrepancy of exposure assessments between numerical models which take account of gravitational effects and the well-mixed model. A new Eulerian-type drift-flux model has been developed to simulate particle dispersion and personal exposure in a two-zone geometry, which accounts for the drift velocity resulting from gravitational settling and diffusion. To validate the numerical model, a small-scale chamber was fabricated. The airflow characteristics and particle concentrations were measured by a phase Doppler Anemometer. Both simulated airflow and concentration profiles agree well with the experimental results. A strong inhomogeneous concentration was observed experimentally for 10μm aerosols. The computational model was further applied to study a simple hypothetical, yet more realistic scenario. The aim was to explore different levels of exposure predicted by the new model and the well-mixed model. Aerosols are initially uniformly distributed in one zone and subsequently transported and dispersed to an adjacent zone through an opening. Owing to the significant difference in the rates of transport and dispersion between aerosols and gases, inferred from the results, the well-mixed model tends to overpredict the concentration in the source zone, and under-predict the concentration in the exposed zone. The results are very useful to illustrate that the well-mixed assumption must be applied cautiously for exposure assessments as such an ideal condition may not be applied for coarse particles.


title: There Will be Blood

text: Abstract Article highlight based on “Effects of IgG and IgM autoantibodies on non-infected erythrocytes is related to ABO blood group in Plasmodium vivax malaria and is associated with anemia" by Luiza Carvalho Mourão et al.


title: Polymorphism of OAS‐1 determines liver fibrosis progression in hepatitis C by reduced ability to inhibit viral replication

text: Background: Progression of disease after hepatitis C virus (HCV) infection differs among individuals, indicating a possibility of participation of host genetic factors. 2′‐5′‐oligoadenylate synthetase 1 (OAS‐1), an important component of the innate immune system, has an antiviral function, and may therefore have a certain relationship with progression of disease. Aim: To evaluate single nucleotide polymorphisms (SNPs) of OAS‐1 and its relationship with the disease status of HCV infection. Methods: Six SNPs of OAS‐1 were selected and examined in 409 Japanese patients with chronic HCV infection using the TaqMan PCR genotyping method. The relationship of SNP genotypes and clinical manifestations of patients was analysed. Then, a pair of OAS‐1‐expression plasmids mimicking the clinical‐related SNPs were created and transfected into liver cells carrying the HCV subgenomic replicon or the full‐length genome, JFH1, and HCV replication after transfection was compared. Results: Patients with genotypes A/A, A/G and G/G of an SNP of OAS‐1 at the exon 3 of its coding sequence were at gradient increased risks of suffering from higher serum alanine aminotransferase (P<0.001) and aspartate aminotransferase (P=0.001), higher degree of liver fibrosis (P=0.010) and higher presence of liver cirrhosis (P=0.001). By multivariate logistic regression analysis, genotype G/G was an independent factor associated with cirrhosis (P=0.013, odds ratio 3.11, 95% confidence interval 1.27–7.63). In liver cells, OAS‐1 with the G allele showed lower ability to inhibit virus replication than OAS‐1 with the A allele (P=0.004). Conclusions: The SNP of OAS‐1 at the exon 3 of its coding sequence was associated with progression of disease in Japanese patients with HCV infection.


Response to the letter, “The cardiovascular burden of congenital heart disease - not only in times of COVID-19”


title: Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease

text: Abstract Coronavirus papain-like proteases (PLPs or PLpro), such as the one encoded in the genome of the infectious Middle East Respiratory Syndrome (MERS) virus, have multiple enzymatic activities that promote viral infection. PLpro acts as a protease and processes the large coronavirus polyprotein for virus replication. PLpro also functions as both a deubiquitinating (DUB) and deISGylating (deISG) enzyme and removes ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) from cellular proteins. Both DUB and deISG activities are implicated in suppressing innate immune responses; however, the precise role of each activity in this process is still unclear due in part to the difficulties in separating each activity. In this study, we determine the first structure of MERS PLpro in complex with the full-length human ISG15 to a resolution of 2.3 Å. This structure and available structures of MERS PLpro-Ub complexes were used as molecular guides to design PLpro mutants that lack either or both DUB/deISG activities. We tested 13 different PLpro mutants for protease, DUB, and deISG activitites using fluorescence-based assays. Results show that we can selectively modulate DUB activity at amino acid positions 1649 and 1653 while mutation of Val1691 or His1652 of PLpro to a positive charged residue completely impairs both DUB/deISG activities. These mutant enzymes will provide new functional tools for delineating the importance of DUB versus deISG activity in virus-infected cells and may serve as potential candidates for attenuating the MERS virus in vivo for modified vaccine design efforts.


title: Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia

text: Secondary bacterial lung infection by Streptococcus pneumoniae (S. pneumoniae) poses a serious health concern, especially in developing countries. We posit that the emergence of multiantibiotic-resistant strains will jeopardize current treatments in these regions. Deaths arising from secondary infections are more often associated with acute lung injury, a common consequence of hypercytokinemia, than with the infection per se. Given that secondary bacterial pneumonia often has a poor prognosis, newer approaches to improve treatment outcomes are urgently needed to reduce the high levels of morbidity and mortality. Using a sequential dual-infection mouse model of secondary bacterial lung infection, we show that host-directed therapy via immunoneutralization of the angiopoietin-like 4 c-isoform (cANGPTL4) reduced pulmonary edema and damage in infected mice. RNA sequencing analysis revealed that anti-cANGPTL4 treatment improved immune and coagulation functions and reduced internal bleeding and edema. Importantly, anti-cANGPTL4 antibody, when used concurrently with either conventional antibiotics or antipneumolysin antibody, prolonged the median survival of mice compared to monotherapy. Anti-cANGPTL4 treatment enhanced immune cell phagocytosis of bacteria while restricting excessive inflammation. This modification of immune responses improved the disease outcomes of secondary pneumococcal pneumonia. Taken together, our study emphasizes that host-directed therapeutic strategies are viable adjuncts to standard antimicrobial treatments.


title: Patients with Genetic Heart Disease and COVID-19: A Cardiac Society of Australia and New Zealand (CSANZ) Consensus Statement

text: Abstract In the context of the current global COVID-19 pandemic, this Consensus Statement provides current recommendations for patients with, or at risk of developing, genetic heart disease, and for their health care management and service provision in Australia and New Zealand. Apart from general recommendations, there are specific recommendations for the following conditions: cardiomyopathy, Brugada syndrome (including in children), long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Other recommendations are relevant to patient self-care and primary health care.


title: Veterinary waste disposal: Practice and policy in Durban, South Africa (2001–2003)

text: Abstract In South Africa, until recently, veterinary waste has not been included in definitions of health care waste, and so has been neglected as a contributor to the hazardous waste stream. Despite the application of, for example, the “Polluter Pays” principle in South African environmental legislation, to generators of waste, which would include veterinarians, there appears to be little awareness of and even less enforcement of the legislation in this regard. This paper reports on a 2001–2003 survey of management practices of the five waste contractors servicing just over half of the veterinarians in Durban, South Africa’s second largest city. Some of their activities, when evaluated in terms of the legislation, guidelines and policies relating to waste handling and disposal, were found to be non-compliant. Since any discussion on waste management should take cognisance of waste from generation to final disposal, the responsibility of veterinarians as waste generators is also discussed in the light of the recent developments in health care waste management in South Africa. This study presents a review of past and current policies, legislation and guidelines that have application to veterinary waste. This is the first study to address veterinary waste disposal in any South African city.


title: VIROLOGIC STUDIES OF ACUTE RESPIRATORY DISEASE IN YOUNG ADULTS: V. CORONAVIRUS 229E INFECTIONS DURING SIX YEARS OF SURVEILLANCE

text: Hamre, D. and M. Beem (DepL Pediatrics, Univ. of Chicago, Chicago, III. 60637). Virologic studies of acute respiratory disease in young adults. V. Coronavirus 229E infections during six years of surveillance. Am J Epidemiol 96: 94–106, 1972.—In a surveillance study of acute respiratory disease in medical students that spanned six consecutive seasons between 1961 and 1968 and encompassed 937 student years of observation, infection with coronavirus 229E was identified by virus isolation and serologic studies. Virus isolation identified 12 infections, 8 in one season, 4 in another. Complement fixing (CF) antibody titer rises identified 133 infections that occurred in all six seasons of surveillance, involving from 15 to 35% of students in three seasons of “high” prevalence, and 1 to 5% in intervening seasons of “low” prevalence. Infection occurred in a winter-spring seasonal pattern and was associated with acute respiratory illness that was not clinically distinctive. Neutralizing antibody to 229E was commonly present in the sera of the students. The level of this did not appear to influence the occurrence of, or likelihood of illness with, reinfection as judged by CF seroconversion; however, the frequency of significant rise in neutralizing antibody titer with reinfection was inversely related to pre-infection levels of this antibody. Infection with other common respiratory viruses did not stimulate significant CF or neutralizing antibody titer rises to 229E.


title: Urban Fringe Land Use Transitions in Hong Kong: From New Towns to New Development Areas

text: Abstract Land in urban fringe area is the primary source for land supply and development. In Hong Kong (HK), nine new towns have been built in New Territories since 1970s, providing 172.6 km2 built-up land and large amount of residences for 3.4 million people. However, due to land scarcity, development restriction, and social opposition, New Development Area (NDA), as the small-scale extension of New Town (NT), was designated as one of the main approaches for HK medium and long term land supply. To demonstrate the characteristics of urban fringe land use transitions in Hong Kong, literature review and case study were used in this research. The history of new town development and the scheme of new development areas were introduced firstly. Afterwards, the land use features of NT and NDA were compared and the case of Hung Shui Kiu NDA was illustrated. It is concluded that while housing, infrastructure and facility were the main elements in NTs, employment, vibrancy and environment were suggested to be the new compulsory elements in NDAs integrated to the traditional planning concepts. As for the development approach, lease modification was adopted in NDA to allow private landowners directly develop their land, in addition to the traditional development approach of land resumption in NT. It is suggested to ensure the development of NDA, the proposed development plan should be persuasive to provide the optimal land use distribution as a trade-off among the profits of developers, the interests of local villager, government concern and the provision of land for future residents. Also, community engagement will play a more important role in NDA planning process. Referring to the analysis of urban fringe land use transitions and strategies for planning and development, the study would also be helpful to others growing cities.


title: Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler

text: BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.


title: Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike

text: The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 1 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are quite immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cyro-electron microscopy structures of one antibody targeting RBD, a second targeting NTD, and a third bridging RBD and NTD revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.


title: New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis

text: A 24-year-old African-American man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. Our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. Extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. We hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. Severe rhabdomyolysis in G6PD deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. Our case adds to the few existing reports of myolysis in the setting of G6PD deficiency.


Supporting adolescents and young adults exposed to or experiencing violence during the COVID-19 pandemic


title: COVID-19 and fertility: A virtual reality

text: Abstract The COVID-19 pandemic is an extraordinary global situation and all Countries have adopted their own strategies to diminish and eliminate the spread of the virus. All measures are in line with the recommendations provided by WHO. Scientific societies, such as ESHRE and ASRM, have provided recommendations and guidance to overcome and flatten the growing curve of infection in patients that undergo IVF treatments. Although there is no evidence yet that the virus causing COVID-19 may exert negative effects on IVF outcome, fertility treatments have been postponed in order to support the healthcare systems by avoiding additional stress contribution. The possibility of the virus affecting sperm function and egg performance cannot be excluded. Also, an indirect effect of the virus on gametes and embryos during their manipulation cannot be ruled out. This commentary aims to provide some ideas on the possible effect of the virus on gametes and embryos as well as how it can affect the normal functioning of the embryology laboratory.


title: Holistic care for patients with severe coronavirus disease 2019: An expert consensus

text: Abstract Objective To standardize the holistic care for patients with severe coronavirus disease 2019 (COVID-19). Methods The consensus was preliminarily formed by combining relevant literature findings and frontline medical working experiences, and it was eventually confirmed by five rounds of online discussions and expert consultations. Results This consensus included nursing assessment, nursing priorities, nursing goals, and thirteen key points of nursing procedures such as nursing of oxygen therapy and respiratory nursing. Conclusion This scientific and practical consensus guideline can provide clinical guidance on the holistic nursing care of patients with severe COVID-19.


title: Epidemiologic and Clinical Characteristics of Coronavirus and Bocavirus Respiratory Infections after Allogeneic Stem Cell Transplantation: A Prospective Single-Center Study

text: Abstract Epidemiologic data about coronaviruses (CoVs) and human bocavirus (HBoV) in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are scarce. We conducted a prospective longitudinal study on respiratory viral infections (RVIs) in allo-HSCT recipients with respiratory symptoms from December 2013 until June 2016. Respiratory virus in upper and/or lower respiratory tract (URT and LRT) specimens were tested using Luminex xTAG RVP Fast v1 assay. Seventy-nine consecutive allo-HSCT recipients developed a total of 192 virologically documented RVI episodes over 30 months. The median follow-up after RVI was 388 days (range, 5 to 923). CoV or HBoV was detected in 27 of 192 episodes (14%); 18 of 79 recipients (23%) developed a total of 21 CoV RVI episodes, whereas 6 recipients (8%) had 1 HBoV RVI episode each. Fourteen CoV RVI episodes were limited to the URT, whereas 7 affected the LRT. Co-pathogens were detected in 8 (38%) CoV cases. Type OC43 CoV was the dominant type (48%) followed by NL63 (24%), KHU1 (19%), and 229E (9%); the CoV hospitalization rate was 19%, whereas mortality was 5% (1 patient without any other microbiologic documentation). Among the 6 recipients with HBoV (3%), only 1 had LRT involvement and no one died from respiratory failure. In 5 cases (83%) HBoV was detected along with other viral co-pathogens. CoV RVIs are common after allo-HSCT, and in a significant proportion of cases CoV progressed to LRT and showed moderate to severe clinical features. In contrast, HBoV RVIs were rare and mostly presented in the context of co-infections.


Who comes first: rescheduling endoscopic activity after the acute phase of the Covid 19 pandemic


title: Baculovirus expression: tackling the complexity challenge

text: Most essential functions in eukaryotic cells are catalyzed by complex molecular machines built of many subunits. To fully understand their biological function in health and disease, it is imperative to study these machines in their entirety. The provision of many essential multiprotein complexes of higher eukaryotes including humans, can be a considerable challenge, as low abundance and heterogeneity often rule out their extraction from native source material. The baculovirus expression vector system (BEVS), specifically tailored for multiprotein complex production, has proven itself to be uniquely suited for overcoming this impeding bottleneck. Here we highlight recent major achievements in multiprotein complex structure research that were catalyzed by this versatile recombinant complex expression tool.


title: SARS changes the ED paradigm

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease. The SARS outbreak in Singapore started in mid-March 2003. Emergency departments, being the primary portal of entry into the hospitals, had to come up with rapid strategic changes and modifications to accommodate and manage this public health problem effectively. This report discusses the changes in the Department of Emergency Medicine at Singapore General Hospital, the largest public, teaching and tertiary hospital in Singapore, during this outbreak. It will highlight the safety aspects and universal precautions undertaken, the changes to the triage system, working hours, admission policies, as well as the fluctuations in the patient load.


Reply to “The use of traditional Chinese medicines to treat SARS-CoV-2 may cause more harm than good”


title: High-Frequency Oscillatory Ventilation for Adult Patients With ARDS

text: High-frequency oscillatory ventilation (HFOV) is characterized by the rapid delivery of small tidal volumes (Vts) of gas and the application of high mean airway pressures (mPaws). These characteristics make HFOV conceptually attractive as an ideal lung-protective ventilatory mode for the management of ARDS, as the high mPaws prevent cyclical derecruitment of the lung and the small Vts limit alveolar overdistension. In this review, we will summarize the literature describing the use of HFOV in adult patients with ARDS. In addition, we will discuss recent experimental studies of HFOV that have advanced our understanding of its mechanical properties. We identified 2 randomized controlled trials (RCTs) and 12 case series evaluating HFOV in adults with ARDS. In these studies, HFOV appears to be safe and consistently improves oxygenation when used as a rescue mode of ventilation in patients with severe ARDS. The two RCTs comparing HFOV to conventional ventilation revealed encouraging results but failed to show a mortality benefit of HFOV over conventional ventilation. Further research is needed to identify optimal patient selection, technique, the actual Vt delivered, and the role of combining HFOV with other interventions, such as recruitment maneuvers, prone positioning, and nitric oxide.


title: Management in oral and maxillofacial surgery during the COVID-19 pandemic: Our experience

text: Abstract A novel β-coronavirus (2019-nCOV), identified in Wuhan City in the late December 2019, is generating a rapid and tragic health emergency in Italy due to the need to provide assistance to an uncontrollable number of infected patients and, at the same time, treat all the non-deferrable oncological and traumatic maxillofacial conditions. This article summarizes the clinical and surgical experience of Maxillofacial Surgery Unit of “Magna Graecia” University (Catanzaro -Italy) during the COVID-19 pandemic and would like to provide a number of recommendations that should facilitate the scheduling process of surgical activities during the COVID-19 pandemic and reduce the risk of infection among healthcare professionals.


title: Evaluation of Ag nanoparticle coated air filter against aerosolized virus: Anti-viral efficiency with dust loading

text: Abstract In this study, the effect of dust loading on the anti-viral ability of an anti-viral air filter was investigated. Silver nanoparticles approximately 11nm in diameter were synthesized via a spark discharge generation system and were used as anti-viral agents coated onto a medium air filter. The pressure drop, filtration efficiency, and anti-viral ability of the filter against aerosolized bacteriophage MS2 virus particles were tested with dust loading. The filtration efficiency and pressure drop increased with dust loading, while the anti-viral ability decreased. Theoretical analysis of anti-viral ability with dust loading was carried out using a mathematical model based on that presented by Joe et al. (J. Hazard. Mater.; 280: 356-363, 2014). Our model can be used to compare anti-viral abilities of various anti-viral agents, determine appropriate coating areal density of anti-viral agent on a filter, and predict the life cycle of an anti-viral filter.


Letter to the editor Regarding Effects of the COVID-19 Outbreak in Northern Italy: Perspectives from the Bergamo Neurosurgery Department


title: Waterpipe smoking as a public health risk: Potential risk for transmission of MERS-CoV

text: The Middle East Respiratory Syndrome (MERS-CoV) emerged in the Kingdom of Saudi Arabia in 2012 causing a critical challenge to public health. The epidemiology of MERS-CoV remain enigmatic as human-to-human transmission is not fully understood. One possible scenario that might play a role in the virus transmission is the cultural waterpipe smoking. Cafés providing waterpipe smoking in cities within Saudi Arabia have been moved to areas outside city limits that frequently place them close to camels markets. We report results of a surveillance study wherein waterpipe hoses throughout several regions in Saudi Arabia were tested for the presence of MERS-CoV. A total of 2489 waterpipe samples were collected from cities where MERS-CoV cases were continuously recorded. MERS-CoV RNA wasn’t detected in collected samples. Irrespective of the negative results of our survey, the public health risk of waterpipe smoking should not be underestimated. To avoid a possible transmission within country where MERS-CoV is prevalent, we recommend the replacement of resusable hoses with “one-time-use” hoses in addition to a close inspection of waterpipe components to assure the appropriate cleaning and sanitization.


title: Bovine Respiratory Coronavirus

text: Bovine coronaviruses (BCoVs) cause respiratory and enteric infections in cattle and wild ruminants. BCoV is a pneumoenteric virus that infects the upper and lower respiratory tract and intestine. It is shed in feces and nasal secretions and also infects the lung. BCoV is the cause of 3 distinct clinical syndromes in cattle: (1) calf diarrhea, (2) winter dysentery with hemorrhagic diarrhea in adults, and (3) respiratory infections in cattle of various ages including the bovine respiratory disease complex or shipping fever of feedlot cattle. No consistent antigenic or genetic markers have been identified to discriminate BCoVs from the different clinical syndromes. At present, there are no BCoV vaccines to prevent respiratory BCoV infections in cattle, and the correlates of immunity to respiratory BCoV infections are unknown. This article focuses on respiratory BCoV infections including viral characteristics; epidemiology and interspecies transmission; diagnosis, pathogenesis, and clinical signs; and immunity and vaccines.


Coronavirus Disease 2019 in Children: An Invisible Threat Which We Cannot Ignore*


title: Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71

text: We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p = 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (γ-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular γ-interferon (p = 0.04), lower cellular IL-1β (p = 0.04), lower cellular IL-6 (p = 0.04), lower cellular tumor necrosis factor-α response (p = 0.04), and lower cellular macrophage inflammatory protein-1α (p = 0.04) response compared with other cases. Their titers of EV71 neutralizing antibodies demonstrated no difference among cases. These results suggest lower EV71-specific cellular response may be associated with immunopathogenesis of EV71-related pulmonary edema.


title: Vaccinia virus produces late mRNAs by discontinuous synthesis

text: Abstract We describe the unusual structure of a vaccinia virus late mRNA. In these molecules, the protein-coding sequences of a major late structural polypeptide are preceded by long leader RNAs, which in some cases are thousands of nucleotides long. These sequences map to different regions of the viral genome and in one instance are separated from the late gene by more than 100 kb of DNA. Moreover, the leader sequences map either upstream or downstream of the late gene, are transcribed from either DNA strand, and are fused to the late gene coding sequence via a poly(A) stretch. This demonstrates that vaccinia virus produces late mRNAs by tagging the protein-coding sequences onto the 3′ end of other RNAs.


title: Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size

text: Abstract Objectives: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). Design and methods: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. Results: Patients with AMI showed significantly higher serum IP-10 levels (137.5±79.8 pg/mL) than control subjects (91.2±40.1 pg/mL) and patients with AP (93.3±41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. Conclusions: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.


title: Influence of socio-ecological factors on COVID-19 risk: a cross-sectional study based on 178 countries/regions worldwide

text: BACKGROUND: The initial outbreak of COVID-19 caused by SARS-CoV-2 in China in 2019 has been severely tested in other countries worldwide. We aimed to describe the spatial distribution of the COVID-19 pandemic worldwide and assess the effects of various socio-ecological factors on COVID-19 risk. METHODS: We collected COVID-19 pandemic infection data and social-ecological data of 178 countries/regions worldwide from three database. We used spatial econometrics method to assess the global and local correlation of COVID-19 risk indicators for COVID-19. To estimate the adjusted incidence rate ratio (IRR), we modelled negative binomial regression analysis with spatial information and socio-ecological factors. FINDINGS: The study indicated that 37, 29 and 39 countries/regions were strongly opposite from the IR, CMR and DCI index "spatial autocorrelation hypothesis", respectively. The IRs were significantly positively associated with GDP per capita, the use of at least basic sanitation services and social insurance program coverage, and were significantly negatively associated with the proportion of the population spending more than 25% of household consumption or income on out-of-pocket health care expenses and the poverty headcount ratio at the national poverty lines. The CMR was significantly positively associated with urban populations, GDP per capita and current health expenditure, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives, and poverty headcount ratio at the national poverty lines. The DCI was significantly positively associated with urban populations, population density and researchers in R&D, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives and poverty headcount ratio at the national poverty lines. We also found that climatic factors were not significantly associated with COVID-19 risk. CONCLUSION: Countries/regions should pay more attention to controlling population flow, improving diagnosis and treatment capacity, and improving public welfare policies.


title: The Microbiome in Cystic Fibrosis

text: Observations from studies during the last decade have changed our conventional view of CF microbiology, which has traditionally focused on a relatively limited suite of opportunistic bacterial pathogens. Much of this change has been driven by the application of next-generation DNA sequencing technology to better assess the microbiota in CF respiratory specimens. We now appreciate that CF airways typically harbor complex microbial communities, and that changes in the structure and activity of these communities has bearing on patient clinical condition and lung disease progression. Recently, studies of gut microbiota suggest that the disordered bacterial ecology of the CF gastrointestinal tract is associated with lung pathology. Although challenges to a more complete understanding of the role lung and gut microbiota play in disease progression remain, these new insights provide exciting prospects to reconsider clinical management of CF.


title: Forecasting the Impact of Coronavirus Disease During Delivery Hospitalization: An Aid for Resources Utilization

text: Abstract Background The ongoing Coronavirus disease (COVID-19) pandemic has severely impacted the United States. In cases of infectious disease outbreak, forecasting models are often developed for resources utilization. Pregnancy and delivery pose unique challenges, given the altered maternal immune system and the fact that the majority of American women choose to deliver in the hospital setting. Objectives The aim of our study is to forecast the incidence of COVID-19 in general population and to forecast the overall incidence, severe cases, critical cases and fatal COVID-19 cases during delivery hospitalization in the United States. Study design We use a phenomenological model with generalized logistic growth models to forecast the incidence of COVID-19 in the United States from 4/15/2020 – 12/31/2020. Incidence data from 3/1/2020 – 4/14/2020 were used to provide best-fit model solution. Subsequently, Monte-Carlo simulation was performed for each week from 3/1/2020 – 12/31/2020 to estimate the incidence of COVID-19 in delivery hospitalizations using the available data estimate. Results From 3/1/2020 – 12/31/2020, our model forecasted a total of 860,475 cases of COVID-19 in general population across the United States. The cumulative incidence for COVID-19 during delivery hospitalization is anticipated to be 16,601 (95% CI, 9,711 – 23,491) cases. Among those, 3,308 (95% CI, 1,755 – 4,861) cases are expected to be severe, 681 (95% CI, 1324 – 1,038) critical and 52 (95% CI, 23 – 81) maternal mortality. Assuming similar baseline maternal mortality rate as the year of 2018, we projected an increase in maternal mortality rate in the US to at least 18.7 (95% CI, 18.0 – 19.5) deaths per 100,000 live birth as a direct result of COVID-19. Conclusions COVID-19 infection in pregnant women is expected to severely impact obstetrical care. From 3/1/2020 – 12/31/2020, we project 3,308 severe and 681 critical cases, with about 52 COVID-19 related maternal mortalities during delivery hospitalization in the United States. These data might be helpful for counseling and resource allocation.


title: Innate immune response induced by Theiler's murine encephalomyelitis virus infection

text: Although the causative agents of human multiple sclerosis (MS) are not known, it is suspected that a viral infection may be associated with the initiation of the disease. Several viral disease models in mice have been studied to understand the pathogenesis of demeylination. In particular, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) has been extensively studied as a relevant model. Various cytokines and chemokines are produced upon viral infection by different cell types, including antigen-presenting cells (APCs) such as macrophages; dendritic cells (DCs); and glial cells, such as astrocytes, microglia, and oligoden-drocytes. The upregulation of the corresponding molecules are also found in MS and are likely to play an important role in the protection and/or pathogenesis of chronic inflammatory demyelinating disease. In this review, the type of cells and molecules, gene-activation mechanisms as well as their potential roles in protection and pathogenesis will be discussed.


title: How can dentistry get back to work safely?

text: Data sources Narrative review Study abstract This review provides a synopsis of our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease, COVID-19. The virus is shed in the nasopharyngeal and salivary secretions of carriers, and this puts dental professionals at risk for increased exposure of SARS-CoV-2. The paper summarises the current guidelines outlined by the CDC and presents the triaging protocols to identify potential carriers and how to safely limit treatment to low-risk patients.


title: IL-15-independent antiviral function of primary and memory CD8+ T cells

text: Abstract Memory CD8+ T cells are comprised of CD122hi IL-15-dependent and CD122lo IL-15-independent subsets. Induction and retention of IL-15-independent memory CD8+ T cells was assessed in IL-15−/− and wild-type (wt) mice immunized with recombinant vaccinia virus (rVV) or Sindbis virus (rSIN) vectors expressing the identical foreign epitope. Both vectors induced epitope-specific CD8+ T cell expansion and function, independent of IL-15. Similar kinetics of rVV clearance confirmed effective CD8+ T cell function in IL-15−/− mice. CD44hi CD122hi CD8+ T cells, mainly of the CD62L−/lo phenotype, increased more dramatically and declined more rapidly in IL-15−/− mice, independent of the vector. Rapid IL-15-independent memory CD8+ T cell expansion following challenge of immune mice compensated for the limited memory CD8+ populations in IL-15−/− mice. However, despite expansion and expression of potent effector function, viral clearance was delayed in the absence of IL-15, coinciding with a rapid loss in cytolytic function.


title: Viral respiratory infections in cystic fibrosis

text: Abstract Viral respiratory infections in CF patients are associated with an increase in morbidity at short and long term. Viral infections have a greater impact on CF patients compared to non-CF controls. They result in increased respiratory symptoms, deterioration of Shwachman and radiological scores, prolonged hospitalizations, a persistent decrease of pulmonary function, increased use of antibiotics and a higher frequency of exacerbations at follow-up. In addition, interaction between viruses and bacteria in CF is suggested. Some studies observe increased new bacterial colonization and raised antipseudomonal antibodies in episodes of viral respiratory infections. Experimental data suggest that increased virus replication, impaired specific anti-bacterial defense and increased adherence of bacteria play a role in the pathogenesis of viral respiratory infections in CF. Further knowledge about the role of viruses and interaction with bacteria in CF lung disease might result in new therapeutic strategies to improve prognosis of CF patients.


title: Coping with hypoxemia: Could erythropoietin (EPO) be an adjuvant treatment of COVID-19?

text: A very recent epidemiological study provides preliminary evidence that living in habitats located at 2500 m above sea level and higher might protect from the development of severe respiratory symptoms following infection with the novel SARS-CoV-2 virus. This epidemiological finding raises the question of whether physiological mechanisms underlying the acclimatization to high altitude identifies therapeutic targets for the effective treatment of severe acute respiratory syndrome pivotal to the reduction of global mortality during the COVID-19 pandemic. This article compares the symptoms of acute mountain sickness (AMS) with those of SARS-CoV-2 infection and explores overlapping patho-physiological mechanisms of the respiratory system including impaired oxygen transport, pulmonary gas exchange and brainstem circuits controlling respiration. In this context, we also discuss the potential impact of SARS-CoV-2 infection on oxygen sensing in the carotid body. Finally, since erythropoietin (EPO) is an effective treatment for AMS, this article reviews the potential benefits of implementing FDA-approved erythropoietin-based (EPO) drug therapies to counteract a variety of acute respiratory and non-respiratory (e.g. excessive inflammation of vascular beds) symptoms of SARS-CoV-2 infection. High-altitude environments of 2500 m above sea level (masl) are characterized by barometric hypoxia. Chronic exposure to hypobaric hypoxia in such extreme and adverse environments evokes short- and long-term physiologic adaptations to maintain tissue oxygen levels at high altitude in animals and humans. Recent work suggests that high altitude dewellers, in particular in American countries and Tibet (Arias-Reyes et al., 2020; Ortiz-Prado et al., 2020), may present with lower infection rates and/or less severe symptoms of COVID-19 compared to lowlanders (Arias-Reyes et al., 2020; Lei et al., 2020; Ortiz-Prado et al., 2020). This epidemiologic finding raises the question of whether physiological mechanisms underlying the acclimatization to high altitude or in turn the development of acute mountain sickness (AMS), may provide potential avenues for understanding the severity of symptoms and treatment of SARS-CoV-2 infection. Here, we provide a survey of similarities of acute mountain sickness to COVID-19 and suggest that the physiologic response to high altitude, characterized by an increase in erythropoietin (EPO), may provide a framework to develop an adjuvant therapy in COVID-19. Indeed, a recently published case study from Iran supports EPO as an effective treatment of severe COVID-19 patho-physiology (Hadadi et al., 2020).


title: Cluster of necrotizing enterocolitis in a neonatal intensive care unit: New Mexico, 2007

text: BACKGROUND: Although the cause of necrotizing enterocolitis (NEC) is unknown, infection control practices have been shown to play an important role in containing many outbreaks. We investigated the etiology of a cluster of NEC in a level 3 neonatal intensive care unit and monitored for new cases following the implementation of enhanced infection control measures. METHODS: Investigators performed a chart and laboratory review for neonates with a diagnosis of NEC during January 1, 2007, to February 13, 2007, to identify risk factors. Enhanced environmental cleaning, cohorting of infants and nurses, and increased attention to hand hygiene were instituted. Commercial feeding products in the unit were tested for bacterial contamination. Close monitoring for new cases continued for 2 months following the identification of the cluster. RESULTS: Eleven cases of NEC were identified during the study period. Patients had a median of 5 disease risk factors (range, 3-8). Four distinct pathogens were detected in blood or stool specimens from 4 different patients. One sample of human milk fortifier (HMF) tested contained a colony count of Bacillus cereus at the US Food and Drug Administration's upper microbiologic limit for contamination. Seven (65%) patients received HMF before symptom onset, and 9 (82%) patients received 1 or more types of liquid formula. Only 1 new case was identified during the period of close monitoring. CONCLUSION: A microbiologic cause was not identified, and, although the cluster might have resolved spontaneously, enhanced infection control and changing batches of HMF might have played a role in controlling this outbreak.


Observation and consideration on using of JAKi in clinical trials in times of COVID‐19


title: Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory

text: Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage ΦX174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.


title: A Mathematical Model of the Evolution and Spread of Pathogenic Coronaviruses from Natural Host to Human Host

text: Coronaviruses are highly transmissible and are pathogenic viruses of the 21(st) century worldwide. In general, these viruses are originated in bats or rodents. At the same time, the transmission of the infection to the human host is caused by domestic animals that represent in the habitat the intermediate host. In this study, we review the currently collected information about coronaviruses and establish a model of differential equations with piecewise constant arguments to discuss the spread of the infection from the natural host to the intermediate, and from them to the human host, while we focus on the potential spillover of bat-borne coronaviruses. The local stability of the positive equilibrium point of the model is considered via the Linearized Stability Theorem. Besides, we discuss global stability by employing an appropriate Lyapunov function. To analyze the outbreak in early detection, we incorporate the Allee effect at time t and obtain stability conditions for the dynamical behavior. Furthermore, it is shown that the model demonstrates the Neimark-Sacker Bifurcation. Finally, we conduct numerical simulations to support the theoretical findings.


Invisible spread of SARS-CoV-2 – Authors' reply


title: Covert Covid-19: CBCT Lung Changes in An Asymptomatic Patient Receiving Radiotherapy

text: INTRODUCTION: COVID-19 profoundly impacted the United States, with New York City (NYC) rapidly becoming the epicenter of the disease. Cancer patients represent a vulnerable population in this pandemic, with data suggesting a higher risk for severe events and unfavorable outcomes. Timely identification of COVID-19 in cancer patients has been thwarted by the lack of outpatient testing for SARS-CoV-2. Chest computed tomography (CT) plays a major role in the identification of COVID-19 pneumonia, with radiologic hallmarks including bilateral, peripheral ground-glass opacities (GGOs) and consolidation. Cancer patients undergoing radiotherapy (RT) commonly have daily cone beam computed tomography (CBCT) obtained for image-guided radiotherapy (IGRT), and such imaging frequently includes the chest. METHODS: We retrospectively reviewed the CBCTs of an initially asymptomatic patient undergoing IGRT for breast cancer, who developed COVID-19 symptoms during the second week of RT. Lung windows of daily CBCTs were reviewed with Diagnostic Radiology to survey for changes consistent with COVID-19. Diagnostic CTs obtained at the time of recovery were obtained and compared with the CBCTs. RESULTS: Five consecutive CBCTs were retrospectively reviewed. Bilateral, peripheral GGOs were noted on the 4(th) and 5(th) CBCTs in the two days prior to symptom onset. CBCT on the day of RT resumption demonstrated substantial worsening of the GGO compared with those obtained during the asymptomatic phase. Diagnostic CTs demonstrated bilateral, peripheral GGOs and mediastinal lymphadenopathy, findings suggesting COVID-19 pneumonitis. Repeat diagnostic CT three days later showed improved pulmonary findings and the patient resumed RT without incident. CONCLUSION: Familiarity with typical CT changes of COVID-19 pneumonitis may allow for early detection in cancer patients undergoing CBCT for RT treatment. Prompt review of the lung windows is recommended in order to identify such changes, with the hope that pre-symptomatic diagnosis leads to expedited patient management, improved outcomes, and a reduction of inadvertent COVID-19 dissemination.


title: Ebola sGP—The first viral glycoprotein shown to be C-mannosylated

text: Abstract Mass spectrometry analysis of the Ebola virus soluble glycoprotein sGP identified a rare post-translation modification, C-mannosylation, which was found on tryptophan (W) 288. This modification has not been described for any other viral protein; however, many viral transmembrane glycoproteins contain one or more of the recognition motifs (W-x-x-W). Elimination of the C-mannose on sGP did not significantly alter protein biosynthesis, processing or structure. Furthermore, the protective effect of sGP on endothelial barrier function, currently the only known activity of sGP, was unaltered. It is possible that C-mannosylation may be a common post-translational modification of viral transmembrane glycoproteins where it could play a role in particle maturation and/or entry by stabilizing the structure of these proteins. In this regard, C-mannosylation of sGP may be an anomaly resulting from the unique manner in which this protein is generated as the product of unedited transcripts from the glycoprotein gene of Ebola.


Understanding Surgical Risk During COVID-19 Pandemic: The Rationale Behind the Decisions


title: Influences of cyclosporin A and non-immunosuppressive derivatives on cellular cyclophilins and viral nucleocapsid protein during human coronavirus 229E replication

text: Abstract The well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin inhibitors abolish this interaction. Upon infection, cyclophilin A stays evenly distributed throughout the cell, whereas cyclophilin B concentrates at ER-bleb-like structures. We further show the inhibitory potential of non-immunosuppressive CsA derivatives Alisporivir, NIM811, compound 3 on HCoV-229E-GFP and -Luciferase replication in human Huh-7.5 hepatoma cells at 18 and 48 h time points post infection with EC50 s at low micromolar ranges. Thus, non-immunosuppressive CsA derivatives effectively inhibit HCoV-229E replication suggesting them as possible candidates for the treatment of HCoV infection. The interruption of interaction between CypA and N protein by CsA and its derivatives suggest a mechanism how CypA inhibitors suppress viral replication.


title: Detection of two porcine circovirus type 2 genotypic groups in United States swine herds

text: In late 2005, sporadic cases of an acute onset disease of high mortality were observed in 10- to 16-week-old growing pigs among several swine herds of the United States. Tissues from the affected pigs in Kansas, Iowa, and North Carolina were examined, and porcine circovirus type 2 (PCV2) was detected consistently among these tissues. Phylogenetically, PCV2 can be divided into two major genotypic groups, PCV2-group 1 and PCV2-group 2. Whereas PCV2-group 1 isolates were detected in all the diseased animals, only two of the diseased animals harbored PCV2-group 2 isolates. This observation is important because PCV2-group 1 isolates had never been reported in the United States before (GenBank as of May 16, 2006), and they are closely related to the PCV2-group 1 isolates that have been described in Europe and Asia, previously. Our analysis revealed that each genotypic group contains a distinct stretch of nucleotide or amino acid sequence that may serve as a signature motif for PCV2-group 1 or PCV2-group 2 isolates.