title: A novel Coltivirus-related virus isolated from free-tailed bats from Côte d’Ivoire is able to infect human cells in vitro

text: BACKGROUND: Zoonotic transmission events play a major role in the emergence of novel diseases. While such events are virtually impossible to predict, wildlife screening for potential emerging pathogens can be a first step. Driven by recent disease epidemics like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, bats have gained special interest as reservoirs of emerging viruses. METHODS: As part of a bigger study investigating pathogens in African bats we screened animals for the presence of known and unknown viruses. RESULTS: We isolated and characterised a novel reovirus from blood of free-tailed bats (Chaereophon aloysiisabaudiae) captured in 2006 in Côte d’Ivoire. The virus showed closest relationship with two human pathogenic viruses, Colorado tick fever virus and Eyach virus, and was able to infect various human cell lines in vitro. CONCLUSION: The study shows the presence of a coltivirus-related virus in bats from Sub-Sahara Africa. Serological studies could help to assess its impact on humans or wildlife health.


title: Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9

text: Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China's infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2) prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3) increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.


title: RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination

text: Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity. The availability of a “universal” method to create attenuated viruses for use as vaccine strains would permit a rapid response to outbreaks of newly emerging viruses. Targeting RdRp fidelity has emerged as such a universal approach. However, because polymerase fidelity and speed are inextricably linked, the effort to attribute the attenuated phenotype to a single biochemical property of the RdRp may be futile. Here, we show that this circumstance is even more complex. We provide evidence for the existence of a biochemical parameter that combines with fidelity and speed to govern the mechanism and/or efficiency of recombination. We conclude that the field will be served best by continued emphasis on discovery of manipulatable functions of the RdRp instead of debating the importance of individual properties.


title: Astroviruses in Dogs

text: Canine astroviruses appear to be widespread geographically. The prevalence may be significantly higher in pups with gastroenteric disease than in asymptomatic animals and virus shedding has been shown to correlate with gastroenteric signs in naturally infected dogs. Animal experiments are required to understand better the pathogenic role of astroviruses in dogs.


title: B-Cell Engineering: A promising approach towards vaccine development for COVID-19

text: With the number of cases crossing three million (and more than two hundred and fifty thousand deaths) worldwide, there is a dire need of a vaccine (and repurposing of drugs) for SARS-CoV-2 disease (COVID-19). It can be argued that a vaccine may be the most efficient way to contain the spread of this disease and prevent its future onset. While many attempts are being made to design and develop a vaccine for SARS-CoV-2, pertinent technological hitches do exist. That is perhaps one of the reasons that we don’t have vaccine for coronaviruses (including SARS-CoV-1 and MERS). Recently developed CRISPR-mediated genome editing approach can be repurposed into a cell modification endeavor rather than correcting defective parts of genome. With this premise, B-cells can be engineered into universal donor, antigen specific, perpetually viable, long lasting, non-oncogenic, relatively benign, antibody producing cells which may serve as an effective vaccine for SARS-CoV-2 and, by the same rationale, other viruses and pathogens.


title: Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola

text: The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537)), 1.2101 (95% CI (1.2084, 1.2119)), 3.0234 (95% CI (2.6063, 3.4881)), and 1.9018 (95% CI (1.8565, 1.9478)), the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958)), 3916 (95% CI (3865, 3967)), 9886 (95% CI (9740, 10031)), and 12633 (95% CI (12515, 12750)) for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.


title: The Promise of Molecular Imaging in the Study and Treatment of Infectious Diseases

text: Infectious diseases are a major threat to humanity, and it is imperative that we develop imaging tools that aid in their study, facilitate diagnosis, and guide treatment. The alarming rise of highly virulent and multi-drug-resistant pathogens, their rapid spread leading to frequent global pandemics, fears of bioterrorism, and continued life-threatening nosocomial infections in hospitals remain as major challenges to health care in the USA and worldwide. Early diagnosis and rapid monitoring are essential for appropriate management and control of infections. Tomographic molecular imaging enables rapid, noninvasive visualization, localization, and monitoring of molecular processes deep within the body and offers several advantages over traditional tools used for the study of infectious diseases. Noninvasive, longitudinal assessments could streamline animal studies, allow unique insights into disease pathogenesis, and expedite clinical translation of new therapeutics. Since molecular imaging is already in common use in the clinic, it could also become a valuable tool for clinical studies, for patient care, for public health, and for enabling precision medicine for infectious diseases.


title: ISG15 and immune diseases

text: Abstract ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein, consisting of two ubiquitin-like domains. ISG15 is synthesized as a precursor in certain mammals and, therefore, needs to be processed to expose the C-terminal glycine residue before conjugation to target proteins. A set of three-step cascade enzymes, an E1 enzyme (UBE1L), an E2 enzyme (UbcH8), and one of several E3 ligases (e.g., EFP and HERC5), catalyzes ISG15 conjugation (ISGylation) of a specific protein. These enzymes are unique among the cascade enzymes for ubiquitin and other ubiquitin-like proteins in that all of them are induced by type I IFNs or other stimuli, such as exposure to viruses and lipopolysaccharide. Mass spectrometric analysis has led to the identification of several hundreds of candidate proteins that can be conjugated by ISG15. Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. However, relatively little is known about the functional significance of ISG15 induction due to the lack of information on the consequences of its conjugation to target proteins. Here, we describe the recent progress made in exploring the biological function of ISG15 and its reversible modification of target proteins and thus in their implication in immune diseases.


title: Death certification in COVID-19 cases in Spain

text: Abstract Death certification requires the same effort and dedication as all reports by doctors during their patients’ lifetimes. The physician must follow the basic instructions to complete a death certificate correctly, taking special care to fill in the sequence of causes of death. In the case of a pandemic, completion of the death certificate falls to the primary care physician and therefore the official bodies must publish instructions based on international recommendations. It should be established as soon as possible whether it is possible to report deaths telematically. While this is not possible, in a pandemic procedures should be put in place to enable the immediate reporting of deaths to the health authorities.


title: The need to include animal protection in public health policies

text: Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and policy development.


title: “You Need ID to Get ID”: A Scoping Review of Personal Identification as a Barrier to and Facilitator of the Social Determinants of Health in North America

text: Personal identification (PID) is an important, if often overlooked, barrier to accessing the social determinants of health for many marginalized people in society. A scoping review was undertaken to explore the range of research addressing the role of PID in the social determinants of health in North America, barriers to acquiring and maintaining PID, and to identify gaps in the existing research. A systematic search of academic and gray literature was performed, and a thematic analysis of the included studies (n = 31) was conducted. The themes identified were: (1) gaining and retaining identification, (2) access to health and social services, and (3) facilitating identification programs. The findings suggest a paucity of research on PID services and the role of PID in the social determinants of health. We contend that research is urgently required to build a more robust understanding of existing PID service models, particularly in rural contexts, as well as on barriers to accessing and maintaining PID, especially among the most marginalized groups in society.


title: Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons

text: The aim of this study was to determine the causative agent of acute respiratory infection (ARI) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV) (28.6%), followed by parainfluenza viruses (PIVs) types 1–3 (18.4%), rhinovirus (HRV) (14.3%), human metapneumovirus (10.1%), adenovirus (AdV) (7.1%), influenza viruses types A and B (4.8%), and coronaviruses (4.2%). In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%), bocavirus (HBoV) (10.5%), PIV-4 (2.6%), and parechovirus (1.3%). There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P > 0.05). AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P < 0.001).


title: Chapter 5 Allograft Tissue Safety and Technology

text: Abstract Allograft tissues are commonly used by orthopedic surgeons and are processed using a variety of technologies to increase safety and clinical use. For safety, although disease transmission is a tangible risk, this possibility has been dramatically minimized through modern tissue-processing methods. These include steps to prevent processing tissues with unacceptable bioburden through rigorous screening using donor medical and social histories along with microbial testing of recovered tissue and viral testing of donor serum. Potential bioburden is also controlled through aseptic recovery and processing methods and then reduced through disinfection steps that can include antibiotics, detergents, mechanical process, chemical solutions, and terminal sterilization. Processing steps may also include decellularization methods to lower immunogenic potential of some tissues. To enhance fusion potential of bone void fillers, demineralization steps may be used, and the resultant demineralized bone matrices may be combined with a carrier to improve handling. Bone void fillers and osteochondral allografts may also be specially processed to retain a living cellular component. To preserve relevant biological, biochemical, and physical properties of allografts for clinical use and ease of handling, a number of methods may be used which include: (1) refrigeration in media, (2) freeze-drying, (3) cryopreservation, (4) freezing, and (5) media storage at room temperature. As academic and industry research continue to drive advances, the future direction of allograft tissue likely includes injectables, coatings, cellular therapies, and combinations with other materials. The technology approaches outlined here will be further described along with future directions.


title: Human rhinovirus C: a newly discovered human rhinovirus species

text: Although often ignored, human rhinoviruses (HRVs) are the most frequent causes of respiratory tract infections (RTIs). A group of closely related novel rhinoviruses have recently been discovered. Based on their unique phylogenetic position and distinct genomic features, they are classified as a separate species, HRV-C. After their discovery, HRV-C viruses have been detected in patients worldwide, with a reported prevalence of 1.4–30.9% among tested specimens. This suggests that the species contribute to a significant proportion of RTIs that were unrecognized in the past. HRV-C is also the predominant HRV species, often with a higher detection rate than that of the two previously known species, HRV-A and HRV-B. HRV-C infections appear to peak in fall or winter in most temperate or subtropical countries, but may predominate in the rainy season in the tropics. In children, HRV-C is often associated with upper RTIs, with asthma exacerbation and wheezing episodes being common complications. The virus has also been detected in children with bronchitis, bronchiolitis, pneumonia, otitis media, sinusitis and systemic infections complicated by pericarditis. As for adults, HRV-C has been associated with more severe disease such as pneumonia and exacerbation of chronic obstructive pulmonary disease. However, larger clinical studies with asymptomatic controls are required to better define the significance of HRV-C infection in the adult population. On the basis of VP4 sequence analysis, a potential distinct subgroup within HRV-C has also been identified, although more complete genome sequences are needed to better define the genetic diversity of HRV-C.


title: Circulation of Respiratory Viruses Among Pilgrims During the 2012 Hajj Pilgrimage

text: Background. The Hajj is the oldest and largest annual mass gathering in the world and may increase the risk of spread of respiratory viruses. Methods. We performed a prospective survey among a cohort of pilgrims departing from Marseille, France, to Mecca in the Kingdom of Saudi Arabia (KSA) for the 2012 Hajj season. Nasal swabs were collected from participants and tested for 11 respiratory viruses by real-time reverse transcription polymerase chain reaction. Results. Of 165 participants sampled before departing to the KSA, 8 (4.8%) were positive for at least 1 virus (5 rhinovirus, 1 influenza C, 1 adenovirus, and 1 enterovirus). Seventy symptomatic pilgrims underwent additional nasal swabs during their pilgrimage in the KSA, of which 27 (38.6%) were positive for at least 1 virus (19 rhinovirus, 6 influenza A, 1 influenza C, 1 respiratory syncytial virus B, 1 metapneumovirus, 1 adenovirus, and 1 enterovirus). This was significantly higher than the 4.8% who were positive before departing for the KSA (P < .001). Of 154 pilgrims sampled before leaving the KSA, 17 (11%) were positive for at least 1 virus (13 rhinovirus, 3 adenovirus, 2 influenza B, and 1 enterovirus), which was also significantly higher than the percentage of positive pilgrims (4.8%), before departing for the KSA (P = .040). Conclusions. This study suggests a rapid acquisition of respiratory viruses among pilgrims during their stay in the KSA, most notably rhinovirus, and highlights the potential of spreading these infections in the pilgrims' home countries upon their return.


title: Dual Modes of Modification of Hepatitis A Virus 3C Protease by a Serine-derived β-Lactone: Selective Crystallization and Formation of a Functional Catalytic Triad in the Active Site

text: Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine proteases responsible for the processing of the viral polyprotein, a function essential for viral maturation and infectivity. This and its structural similarity to other 3C and 3C-like proteases make it an attractive target for the development of antiviral drugs. Previous solution NMR studies have shown that a Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties indistinguishable from the native enzyme, is irreversibly inactivated by N-benzyloxycarbonyl-l-serine-β-lactone (1a) through alkylation of the sulfur atom at the active site Cys172. However, crystallization of an enzyme–inhibitor adduct from the reaction mixture followed by X-ray structural analysis shows only covalent modification of the ε2-nitrogen of the surface His102 by the β-lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple quantum coherence (HMQC) NMR spectra of the enzyme–inhibitor mixture indicates that dual modes of single covalent modification occur with a ≥3:1 ratio of S-alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes readily, probably due to the interaction between the phenyl ring of the N-benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring protein molecule in the crystal. Furthermore, significant structural changes are observed in the active site of the 3C protease, which lead to the formation of a functional catalytic triad with Asp84 accepting one hydrogen bond from His44. Although the 3C protease modified at Cys172 is catalytically inactive, the singly modified His102 Nε2-alkylated protein displays a significant level of enzymatic activity, which can be further modified/inhibited by N-iodoacetyl-valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount of the same β-lactone inhibitor (in solution). The success of soaking IVF into HAV 3C–1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme–inhibitor interactions in the proteolytic active site.


title: Rapid detection of respiratory organisms with the FilmArray respiratory panel in a large children’s hospital in China

text: BACKGROUND: Respiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections. METHODS: Nasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae). RESULTS: Among the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis. CONCLUSIONS: FilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3429-6) contains supplementary material, which is available to authorized users.


title: Continuous positive airway pressure to avoid intubation in SARS-CoV-2 pneumonia: a two-period retrospective case-control study

text: COVID-19 pneumonia can be life-threatening. Given the unprecedented burden place on ICU resources by the epidemic, avoiding intubation is a major issue. This study suggests that CPAP can achieve this objective.


Changes in Interventional Radiology Practice in a Tertiary Academic Center in the United States during the COVID-19 Pandemic


title: The Oxford Royal College of General Practitioners Clinical Informatics Digital Hub: Protocol to Develop Extended COVID-19 Surveillance and Trial Platforms

text: BACKGROUND: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. OBJECTIVE: The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. METHODS: We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. RESULTS: The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. CONCLUSIONS: ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19773


title: Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study

text: Abstract Background Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9•5 109/L) or lymphopenia (<1•1 109/L). Findings Normal or decreased number of leukocytes (≤9•5 109/L), lymphopenia (<1•1 109/L), eosinopenia (<0•02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95•0%, 52•2%, 74•7% and 86•7% of COVID-19 patients, much higher than 87•2%, 28•8%, 31•3% and 45•2% of the controls, respectively. The eosinopenia produced a sensitivity of 74•7% and specificity of 68•7% for separating the two groups with the area under the curve (AUC) of 0•717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67•9% and specificity of 78•2% (AUC=0•730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP).


Therapeutic Plasma Exchange–Neutralizing Antibody Combination Therapy for Severe Coronavirus Disease 2019


title: In vitro analysis of the renin–angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus

text: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin–angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.


title: Clinical and Functional Characterization of URAT1 Variants

text: Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.


title: Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility

text: Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host–pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy.


title: Principles of infection prevention and reprocessing in ENT endoscopy

text: This article gives an overview on the principles of reprocessing of rigid and flexible endoscopes used in ENT units including structural and spatial requirements based on general and ENT-specific risks of infection associated with diagnostic and therapeutic endoscopy. The underlying legal principles as well as recommendations from scientific societies will be exemplified in order to give a practical guidance to the otorhinolaryngologist. Preliminary results of a small nation-wide survey on infection control standards based on data of 29 ENT practices in Germany reveal current deficits of varying degree concerning infection control management including reprocessing of endoscopes. The presented review aims to give support to the establishment of a structured infection control management program including the evaluation of results by means of a prospective surveillance.


title: A combined nucleocapsid vaccine induces vigorous SARS-CD8+ T-cell immune responses

text: Several studies have shown that cell-mediated immune responses play a crucial role in controlling viral replication. As such, a candidate SARS vaccine should elicit broad CD8+ T-cell immune responses. Several groups of mice were immunized alone or in combination with SARS-nucleocapsid immunogen. A high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP as an adjuvant. We also observed that co-administration of a plasmid expressing nucleocapsid, recombinant protein and montanide/CpG induces high antibody titers in immunized mice. Moreover, this vaccine approach merits further investigation as a potential candidate vaccine against SARS.


title: Wrapping Things up about Virus RNA Replication

text: All single‐stranded ‘positive‐sense’ RNA viruses that infect mammalian, insect or plant cells rearrange internal cellular membranes to provide an environment facilitating virus replication. A striking feature of these unique membrane structures is the induction of 70–100 nm vesicles (either free within the cytoplasm, associated with other induced vesicles or bound within a surrounding membrane) harbouring the viral replication complex (RC). Although similar in appearance, the cellular composition of these vesicles appears to vary for different viruses, implying different organelle origins for the intracellular sites of viral RNA replication. Genetic analysis has revealed that induction of these membrane structures can be attributed to a particular viral gene product, usually a non‐structural protein. This review will highlight our current knowledge of the formation and composition of virus RCs and describe some of the similarities and differences in RNA‐membrane interactions observed between the virus families Flaviviridae and Picornaviridae.


title: The politics and ethics of hospital infection prevention and control: a qualitative case study of senior clinicians’ perceptions of professional and cultural factors that influence doctors’ attitudes and practices in a large Australian hospital

text: BACKGROUND: Hospital infection prevention and control (IPC) programs are designed to minimise rates of preventable healthcare-associated infection (HAI) and acquisition of multidrug resistant organisms, which are among the commonest adverse effects of hospitalisation. Failures of hospital IPC in recent years have led to nosocomial and community outbreaks of emerging infections, causing preventable deaths and social disruption. Therefore, effective IPC programs are essential, but can be difficult to sustain in busy clinical environments. Healthcare workers’ adherence to routine IPC practices is often suboptimal, but there is evidence that doctors, as a group, are consistently less compliant than nurses. This is significant because doctors’ behaviours disproportionately influence those of other staff and their peripatetic practice provides more opportunities for pathogen transmission. A better understanding of what drives doctors’ IPC practices will contribute to development of new strategies to improve IPC, overall. METHODS: This qualitative case study involved in-depth interviews with senior clinicians and clinician-managers/directors (16 doctors and 10 nurses) from a broad range of specialties, in a large Australian tertiary hospital, to explore their perceptions of professional and cultural factors that influence doctors’ IPC practices, using thematic analysis of data. RESULTS: Professional/clinical autonomy; leadership and role modelling; uncertainty about the importance of HAIs and doctors’ responsibilities for preventing them; and lack of clarity about senior consultants’ obligations emerged as major themes. Participants described marked variation in practices between individual doctors, influenced by, inter alia, doctors’ own assessment of patients’ infection risk and their beliefs about the efficacy of IPC policies. Participants believed that most doctors recognise the significance of HAIs and choose to [mostly] observe organisational IPC policies, but a minority show apparent contempt for accepted rules, disrespect for colleagues who adhere to, or are expected to enforce, them and indifference to patients whose care is compromised. CONCLUSIONS: Failure of healthcare and professional organisations to address doctors’ poor IPC practices and unprofessional behaviour, more generally, threatens patient safety and staff morale and undermines efforts to minimise the risks of dangerous nosocomial infection.


title: Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?

text: To evaluate the most controversial issue concerning current feline coronavirus (FCoV) virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV) in regard to the pathogenesis of feline infectious peritonitis (FIP), this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M) gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3) from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.


Corona ist doch nicht die Pest!


title: Shining a Light on the Pathogenicity of Health Care Providers' Mobile Phones: Use of a Novel Ultraviolet-C Wave Disinfection Device

text: BACKGROUND: Mobile phones are known to carry pathogenic bacteria and viruses on their surfaces, posing a risk to healthcare providers (HCPs) and hospital infection prevention efforts. We utilize an Ultraviolet-C (UV-C) device to provide an effective method for mobile phone disinfection and survey HCPs about infection risk. METHODS: Environmental swabs were used to culture HCPs’ personal mobile phone surfaces. Four cultures were obtained per phone: before and after the UV-C device's 30-second disinfecting cycle, at the beginning and end of a 12-hour shift. Surveys were administered to participants pre- and post-study. RESULTS: Total bacterial colony forming units (CFUs) were reduced by 90.5% (p=0.006) after one UV-C disinfection cycle, and by 99.9% (p=0.004) after two cycles. Total pathogenic bacterial CFUs were decreased by 98.2% (p=0.038) after one and >99.99% (p=0.037) after two disinfection cycles. All survey respondents were willing to use the UV-C device daily to weekly, finding it convenient and beneficial. DISCUSSION: This novel UV-C disinfecting device is effective in reducing pathogenic bacteria on mobile phones. HCPs would frequently use a phone disinfecting device to reduce infection risk. CONCLUSIONS: In light of the ongoing coronavirus (COVID-19) pandemic, a standardized approach to phone disinfection may be valuable in preventing healthcare-associated infections.


Atypical Lymphocyte Morphology in SARS-CoV-2 Infection


title: Significant concurrent decrease in PM(2.5) and NO(2) concentrations in China during COVID-19 epidemic

text: The strict control measures and social lockdowns initiated to combat COVID-19 epidemic have had a notable impact on air pollutant concentrations. According to observation data obtained from the China National Environmental Monitoring Center, compared to levels in 2019, the average concentration of NO(2) in early 2020 during COVID-19 epidemic has decreased by 53%, 50%, and 30% in Wuhan city, Hubei Province (Wuhan excluded), and China (Hubei excluded), respectively. Simultaneously, PM(2.5) concentration has decreased by 35%, 29%, and 19% in Wuhan, Hubei (Wuhan excluded), and China (Hubei excluded), respectively. Less significant declines have also been found for SO(2) and CO concentrations. We also analyzed the temporal variation and spatial distribution of air pollutant concentrations in China during COVID-19 epidemic. The decreases in PM(2.5) and NO(2) concentrations showed relatively consistent temporal variation and spatial distribution. These results support control of NO(x) to further reduce PM(2.5) pollution in China. The concurrent decrease in NO(x) and PM(2.5) concentrations resulted in an increase of O(3) concentrations across China during COVID-19 epidemic, indicating that coordinated control of other pollutants is needed.


title: Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy

text: BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV – VI). Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties. Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.


title: Arterial and venous strokes in the setting of COVID-19

text: BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID -19) is a global pandemic that causes flu-like symptoms. There is a growing body of evidence suggesting that both the central and peripheral nervous systems can be affected by SARS-CoV-2, including stroke. We present three cases of arterial ischemic strokes and one venous infarction from a cerebral venous sinus thrombosis in the setting of COVID-19 infection who otherwise had low risk factors for stroke. METHODS: We retrospectively reviewed patients presenting to a large tertiary care academic US hospital with stroke and who tested positive for COVID-19. Medical records were reviewed for demographics, imaging results and lab findings. RESULTS: There were 3 cases of arterial ischemic strokes and 1 case of venous stroke: 3 males and 1 female. The mean age was 55 (48-70) years. All arterial strokes presented with large vessel occlusions and had mechanical thrombectomy performed. Two cases presented with stroke despite being on full anticoagulation. CONCLUSIONS: It is important to recognize the neurological manifestations of COVID-19, especially ischemic stroke, either arterial or venous in nature. Hypercoagulability and the cytokine surge are perhaps the cause of ischemic stroke in these patients. Further studies are needed to understand the role of anticoagulation in these patients.


title: Concise Synthesis of Linderaspirone A and Bi‐linderone

text: Photogenic: The synthesis of linderaspirone A has been accomplished in only three steps by a Darzens cyclopentenedione synthesis and dioxygen‐assisted photochemical dimerization. Moreover, the thermal isomerization of linderaspirone A into bi‐linderone has been discovered, which may give clues to the biosynthetic pathway for bi‐linderone.[Image: see text]


title: Vaccination for seasonal influenza in patients with cancer: recommendations of the Italian Society of Medical Oncology (AIOM)

text: BACKGROUND: Influenza virus causes annual epidemics in the winter–spring season with significant morbidity in the general population and important mortality in high-risk groups, including cancer patients. Opinions on the suitability of patients with malignancies not undergoing active treatment and in different phases of antineoplastic therapy, to receive influenza vaccination, vary considerably among oncologists, sometimes even within one center. METHODS: We reviewed available data, including recommendations by national health authorities, on impact of influenza in patients with cancer and their capacity to mount protective immunological responses to vaccination, thus allowing, on behalf of Italian Association of Medical Oncology, to make suitable recommendations for the prevention and treatment of seasonal influenza. RESULTS AND DISCUSSION: Patients with cancer often have disease- or treatment-related immunosuppression, and as a consequence, they may have a suboptimal serologic response to influenza vaccination. The protective effect of the different preparations of influenza vaccines in patients with cancer has not been widely investigated, especially in adult patients harboring solid tumors. The optimal timing for administration of influenza vaccines in patients receiving chemotherapy is also not clearly defined. However, since vaccination is the most effective method, along with antiviral drugs in selected patients, for preventing influenza infection, it has to be recommended for cancer patients. Implementing vaccination of close contacts of oncology patients would be an additional tool for enhancing protection in fragile patient populations.


title: Treatment concerns for bullous pemphigoid in the COVID‐19 pandemic era

text: Bullous pemphigoid (BP) is the most common autoimmune blistering disease with subepidermal involvement, typically affecting the elderly. It has spontaneous remissions and exacerbations with significant morbidity. A novel coronavirus called severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for the new universal coronavirus disease 2019 (COVID‐19) pandemic. The pandemic made concerns, especially about immunosuppressive therapy. In this article, we reviewed the management of BP in the COVID‐19 pandemic era. The data about the best management of autoimmune bullous diseases like BP, during the outbreak of COVID‐19, is evolving and updated every day. This article is protected by copyright. All rights reserved.


title: Consequences of physical distancing emanating from the COVID-19 pandemic: An australian perspective

text: The sobering reality of the COVID-19 pandemic is that it has brought people together at home at a time when we want them apart in the community. This will bring both benefits and challenges. It will affect people differently based upon their age, health status, resilience, family support structures, and socio-economic background. This article will assess the impact in high income countries like Australia, where the initial wave of infection placed the elderly at the greatest risk of death whilst the protective measures of physical distancing, self-isolation, increased awareness of hygiene practices, and school closures with distance learning has had considerable impact on children and families acutely and may have ramifications for years to come.


title: Effects of Coronavirus Infections in Children

text: The isolation of the coronavirus (CoV) identified as the cause of severe acute respiratory syndrome and the detection of 2 new human CoVs (HCoV-NL63 and HCoV-HKU1) have led to studies of the epidemiology and clinical and socioeconomic effects of infections caused by all HCoVs, including those known since the late 1960s (HCoV-229E and HCoV-OC43). HCoV infections can be associated with respiratory and extrarespiratory manifestations, including central nervous system involvement. Furthermore, unlike other RNA viruses, HCoVs can easily mutate and recombine when different strains infect the same cells and give rise to a novel virus with unpredictable host ranges and pathogenicity. Thus, circulating HCoVs should be closely monitored to detect the spread of particularly virulent strains in the community at an early stage and to facilitate the development of adequate preventive and therapeutic measures.


title: Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae)

text: BACKGROUND: The delta smelt (Hypomesus transpacificus) is a pelagic fish species listed as endangered under both the USA Federal and Californian State Endangered Species Acts and considered an indicator of ecosystem health in its habitat range, which is limited to the Sacramento-San Joaquin estuary in California, USA. Anthropogenic contaminants are one of multiple stressors affecting this system, and among them, current-use insecticides are of major concern. Interrogative tools are required to successfully monitor effects of contaminants on the delta smelt, and to research potential causes of population decline in this species. We have created a microarray to investigate genome-wide effects of potentially causative stressors, and applied this tool to assess effects of the pyrethroid insecticide esfenvalerate on larval delta smelt. Selected genes were further investigated as molecular biomarkers using quantitative PCR analyses. RESULTS: Exposure to esfenvalerate affected swimming behavior of larval delta smelt at concentrations as low as 0.0625 μg.L(-1), and significant differences in expression were measured in genes involved in neuromuscular activity. Alterations in the expression of genes associated with immune responses, along with apoptosis, redox, osmotic stress, detoxification, and growth and development appear to have been invoked by esfenvalerate exposure. Swimming impairment correlated significantly with expression of aspartoacylase (ASPA), an enzyme involved in brain cell function and associated with numerous human diseases. Selected genes were investigated for their use as molecular biomarkers, and strong links were determined between measured downregulation in ASPA and observed behavioral responses in fish exposed to environmentally relevant pyrethroid concentrations. CONCLUSIONS: The results of this study show that microarray technology is a useful approach in screening for, and generation of molecular biomarkers in endangered, non-model organisms, identifying specific genes that can be directly linked with sublethal toxicological endpoints; such as changes in expression levels of neuromuscular genes resulting in measurable swimming impairments. The developed microarrays were successfully applied on larval fish exposed to esfenvalerate, a known contaminant of the Sacramento-San Joaquin estuary, and has permitted the identification of specific biomarkers which could provide insight into the factors contributing to delta smelt population decline.


title: Recent Research on Occupational Animal Exposures and Health Risks: A Narrative Review

text: PURPOSE OF REVIEW: In the last year, an increasing number of studies have reported on methicillin-resistant Staphylococcus aureus (MRSA) transmission in Africa and Asia and in migrant workers. We reviewed original research on occupational health and safety of animal workers published from January 1, 2018, through June 30, 2019, with a targeted focus on infectious disease studies published in these populations. RECENT FINDINGS: Studies focused on occupational exposures to infectious agents, dust and allergens, pesticides, and occupational injury. Research on zoonotic MRSA used whole genome–sequencing technologies to evaluate transmission in Africa and Asia. Swine worker exposure to porcine coronavirus and emerging influenza A viruses was documented in China. 16s RNA amplicon sequencing identified distinct microbiota compositions in households with active animal farmers. Multiple bioaerosol exposures were assessed for industrial dairy workers. Occupational injury studies highlighted the struggles of Latino animal workers in the USA. SUMMARY: These studies highlighted the global expansion of zoonotic antibiotic resistance and identified novel occupational zoonoses of concern. The integration of microbiome assessment and compound mixtures into the evaluation of dust and endotoxin exposures for animal workers marks a new direction for this work.


title: Recalibrating Veterinary Medicine through Animal Welfare Science and Ethics for the 2020s

text: SIMPLE SUMMARY: This article emphasizes the importance of educating veterinarians and veterinary students in animal welfare science and veterinary ethics, so that they can ably advance pertinent scientific knowledge and promote ethical thinking as trusted animal advocates in the 2020s. In light of this public expectation, a number of challenges are raised for veterinarians and the veterinary profession. These challenges involve: (1) re-envisioning the nature of disease treatment that goes beyond traditional conceptions of health or clinical matters, and which include animal welfare; (2) re-imagining disease prevention at the intersection of animal-human-ecosystem health; (3) developing core competencies in animal welfare science and ethics in order to provide professional leadership in animal welfare; and (4) taking a more active role in the development of novel networked devices, monitoring technologies and automated animal welfare solutions, and understanding their effects on the welfare of animals, human-animal relationships, and the veterinary profession in general. ABSTRACT: What should leading discourses and innovation regarding animal welfare look like for the veterinary profession in the 2020s? This essay considers four main challenges into which veterinarians are increasingly being drawn, as they respond to increasing public expectation for them to be scientific and moral authorities in animal welfare in addition to their traditional role as trusted health experts. They include: (1) to go beyond traditional conceptions of health by adopting a holistic view that also considers animal welfare, not only disease treatment; (2) to reimagine their professional duties when it comes to disease prevention at the intersection of animal-human-ecosystem health; (3) to develop core competencies/proficiency in animal welfare science and ethics in order to navigate discourses concerning competing priorities and socio-political ideologies and to provide professional leadership in animal welfare; (4) to provide feedback on novel networked devices, monitoring technologies and automated animal welfare solutions and their impact on animals’ welfare. To competently navigate the intricacies of the socio-political and connected world as trusted authorities and conduits for innovation in and through animal welfare, veterinarians and veterinary students are encouraged to: (a) develop core competencies in veterinary ethics, animal welfare science and deliberative capacities that are well-informed by current multidisciplinary frameworks, such as One Health; (b) engage interested parties in more effective collaboration and ethical decision-making in order to address animal welfare related concerns within their immediate sphere of influence (e.g., in a given community); and (c) participate in the process of engineering and technological design that incorporates animals’ welfare data (such as their preferences) for real-time animal monitoring through adding animal scientific and values-aware evidence in information technology systems. In order to tackle these challenges, four pillars are suggested to help guide veterinarians and the veterinary profession. They are: Collaboration, Critical Engagement, Centeredness on Research, and Continuous Self-Critique.


title: Prevalence and Mortality due to Outbreak of Novel Coronavirus Disease (COVID‐19) in β‐Thalassemias: The Nationwide Iranian Experience

text: In late December 2019, an ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection that was termed Coronavirus Disease 2019 (COVID‐19), was reported in Wuhan, China (Zhu, et al 2020).


title: Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs

text: SIMPLE SUMMARY: Porcine epidemic diarrhea virus seriously threatens the health of suckling pigs. In this study, global mapping of H3K4me3 and transcriptomic analyses in the jejunum of porcine epidemic diarrhea virus (PEDV)-infected and healthy piglets were performed by using chromatin immunoprecipitation sequencing and RNA-seq techniques. A subset of genes and H3K4 trimethylation (H3K4me3) histone modifications that are associated with PEDV infections were identified. The results revealed previously unknown and intriguing elements involved in the regulation of genes responsive to PEDV infections, which may aid in identifying key regulators and genetic resistant markers for PEDV infections. ABSTRACT: Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.


title: Fatal case of acute gastroenteritis with multiple viral coinfections

text: Abstract We report a fatal case of acute gastroenteritis in a child with autism spectrum disorder. Multiple viral coinfections were detected by PCR in the patient’s stool and digestive biopsy specimens. As viral detection is not necessarily associated with symptomatic disease, a semi-quantitative approach using cycle treshold values was proposed for the clinical interpretation of PCR. We discuss whether concomitant viral infections could be a risk factor for severe outcome in gastroenteritis cases. Individual risk factors are also addressed.


title: Bronquiectasias

text: Bronchiectasis is defined as irreversible dilatation of the bronchial lumen. Bronchiectasis not due to cystic fibrosis is the third most common chronic inflammatory disease of the airway, after asthma and chronic obstructive pulmonary disease (CPOD). The pathogenesis of the disease is characterised by chronic dilatation, with irreversible and usually progressive destruction of the bronchial wall as a consequence of the vicious pathogenic circle described by E. Cole, of infection, inflammation, injury to the mucociliary system, and cyclical repair of the airway. The disease can have different causes, and usually presents with cough and chronic expectoration, and repeated, acute, infectious exacerbations. Suspected diagnosis is clinical, and must be confirmed by high resolution computerised tomography. The treatment comprises diverse regimens aimed at controlling infection and bronchial inflammation. Nutritional aspects should be considered as part of treatment, as well as the management of secretions, muscle training and the management of complications and comorbidities.


title: Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis—A Prospective Cohort Study

text: Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial virus (RSV), influenza virus A and B, H1N1 virus, parainfluenza virus 1 to 4, metapneumovirus, coronavirus, and picornavirus. Stools were examined for adenovirus, rotavirus, norovirus, and enterovirus. Results Between August 2010 and March 2014, data of 88 infants with 137 episodes of suspected late-onset bacterial sepsis were analyzed. Six infants were diagnosed with a respiratory viral infection (2 × RSV, 4 × picornavirus). Blood culture–proven bacterial sepsis was detected in 15 infants. Neither viral–bacterial coinfections nor polymerase chain reaction positive stool samples were found. Conclusion Respiratory viruses can be detected in a considerable number of neonates with suspected late-onset bacterial sepsis. In contrast, gastrointestinal viral or enterovirus infections appear uncommon in such cases.


In-ICU COVID-19 patients’ characteristics for an estimation in post-ICU rehabilitation care requirement


title: Development and evaluation of enzyme-linked immunosorbent assay based on recombinant nucleocapsid protein for detection of porcine epidemic diarrhea (PEDV) antibodies

text: Abstract An enzyme-linked immunosorbent assays (ELISA) based on recombinant nucleocapsid (N) protein generated in Escherichia coli was evaluated for its sensitivity and specificity for diagnosis of porcine epidemic diarrhea (PEDV) infection. The N gene encoding the N protein was cloned and expressed as a fusion protein with His tag protein in E. coli. The recombinant N protein was migrated at 48kDa and reacted with six histidine tag specific monoclonal antibody by immunoblotting. Recombinant N protein ELISA (rnELISA) demonstrated 98.7% specificities among (80) PEDV-free individuals, and 98% sensitivity ranging among (103) clinical samples with PEDV. On testing 884 field samples, an overall agreement of 88.3% was generated between the SN and rnELISA. Taken together, these results indicated that nucleocapsid protein may be a useful antigen for the sera-diagnosis of PEDV and it was also suggested that the ELISA is a highly sensitive and specific test for detecting antibodies to PEDV.


title: Phenotypic Variations of Cartilage Hair Hypoplasia: Granulomatous Skin Inflammation and Severe T Cell Immunodeficiency as Initial Clinical Presentation in Otherwise Well Child with Short Stature

text: We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with ‘severe and/or combined’ T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.


title: Current and Future Challenges in the Delivery of Mental Healthcare during COVID-19

text: The USA is in the midst of the COVID-19 pandemic. We assess the impact of COVID-19 on psychiatric symptoms in healthcare workers, those with psychiatric comorbidities, and the general population. We highlight the challenges ahead and discuss the increased relevance of telepsychiatry. We analyzed all available literature available as of March 25, 2020, on PubMed, Ovid Medline, and PsychInfo. We utilized the MeSH term “covid AND (psychiatry OR mental health)” and included all articles. Duplicates were removed resulting in 32 articles, of which 19 are cited. Four additional references are included to examine suicide data. During the review process, an additional 7 articles were identified which are also included. Frontline healthcare workers are currently experiencing increased psychiatric symptoms and this is more severe in females and nurses. Non-frontline healthcare workers, as well as the general population, are experiencing vicarious traumatization. People with psychiatric comorbidities, and the general population, face increased psychiatric symptom burden. Migrant workers, the elderly, children, and the homeless may be disproportionately impacted. Suicide rates may be impacted. The COVID-19 pandemic has resulted in a severe disruption to the delivery of mental healthcare. Psychiatric facilities are facing unprecedented disruptions in care provision as they struggle to manage an infected population with comorbid psychiatric symptoms. Telepsychiatry is a flawed but reasonable solution to increase the availability of mental healthcare during COVID-19.


title: Tourism crises and island destinations: Experiences in Penang, Malaysia

text: Abstract Crisis management and tourism is attracting increasing attention as an industry practice and subject of academic enquiry, not least in South East Asia which has been affected by a number of severe crises in recent years. However, organisations are not always well prepared and response strategies can be deficient. The paper discusses issues of tourism crisis management with specific reference to the popular Malaysian destination of Penang. Findings are based on qualitative research consisting of semi-structured interviews with industry leaders from assorted sectors. Tourism in Penang emerges as vulnerable to regional and global events which act as a trigger for tourism crises, demanding a response in which various strategies are employed. The destination is also seen to recover fairly quickly from experiences of crises, but a well designed and formulated tourism crisis management plan under the stewardship of the public sector is necessary to mitigate further damage in the future.


title: Human TLR-7-, -8-, and -9-Mediated Induction of IFN-α/β and -λ Is IRAK-4 Dependent and Redundant for Protective Immunity to Viruses

text: Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-α/β and -λ. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-α/β and -λ induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-α/β and -λ were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-β and -λ were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-α/β and -λ production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-α/β and -λ is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.


title: Risk Parameters of Fulminant Acute Respiratory Distress Syndrome and Avian Influenza (H5N1) Infection in Vietnamese Children

text: A clinical picture of patients with acute respiratory distress syndrome (ARDS) induced by highly pathogenic avian influenza A (H5N1) has been reported. We reviewed 37 sets of clinical data for pediatric patients with ARDS at the National Hospital of Pediatrics (Hanoi, Vietnam); 12 patients with H5N1-positive and 25 with H5N1-negative ARDS were enrolled. The H5N1-negative patients had a clinical picture and mortality rate similar to that for the pediatric ARDS patients. However, the H5N1-positive patients had ARDS with normal ventilation capacity at the time of hospital admission, then rapidly proceeded to severe respiratory failure. The survival probability and days until final outcome in groups of H5N1-positive (n=12) vs. H5N1-negative (n=25) patients were 17% versus 52% and 12.3±5.7 days (median, 11 days) versus 21.5±13.8 days (median, 22 days), respectively. Our observations clarified the clinical picture of H5N1-induced fulminant ARDS and also confirmed that relatively older age (∼6 years of age), high fever at onset, and leukopenia and/or thrombocytopenia at the time of hospital admission are risk parameters for H5N1-induced fulminant ARDS


title: Mitigating the impact of conference and travel cancellations on researchers’ futures

text: The need to protect public health during the current COVID-19 pandemic has necessitated conference cancellations on an unprecedented scale. As the scientific community adapts to new working conditions, it is important to recognize that some of our actions may disproportionately affect early-career researchers and scientists from countries with limited research funding. We encourage all conference organizers, funders and institutions who are able to do so to consider how they can mitigate the unintended consequences of conference and travel cancellations and we provide seven recommendations for how this could be achieved. The proposed solutions may also offer long-term benefits for those who normally cannot attend conferences, and thus lead to a more equitable future for generations of researchers.


Covid-19: Deadline for roll out of UK's tracing app will be missed.


title: Middle East respiratory syndrome: obstacles and prospects for vaccine development

text: The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates in vivo testing of candidate vaccines. Second, due to the low number of MERS cases, pharmaceutical companies have little incentive to pursue MERS vaccine production as the costs of clinical trials are high. In addition, the timeline from bench research to approved vaccine use is 10 years or longer. Using novel methods and cost-saving strategies, genetically engineered vaccines can be produced quickly and cost-effectively. Along with progress in MERS animal model development, these obstacles can be circumvented or at least mitigated.


title: Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage

text: OBJECTIVE: To use Multi-Criteria Decision Analysis (MCDA) to determine weights for eleven criteria in order to prioritize COVID-19 non-critical patients for admission to hospital in healthcare settings with limited resources. METHODS: The MCDA was applied in two main steps: specification of criteria for prioritizing COVID-19 patients (and levels within each criterion); and determination of weights for the criteria based on experts’ knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on low- and middle-income countries (LMICs). RESULTS: The most important criteria (mean weights, summing to 100%), are: PaO(2) (16.3%); peripheral O(2) saturation (15.9%); chest X-ray (14.1%); Modified Early Warning Score-MEWS (11.4%); respiratory rate (9.5%); comorbidities (6.5%); living with vulnerable people (6.4%); body mass index (5.6%); duration of symptoms before hospital evaluation (5.4%); CRP (5.1%); and age (3.8%). CONCLUSIONS: At the beginning of a new pandemic, when evidence for disease predictors is limited or unavailable and effective national contingency plans are difficult to establish, the MCDA prioritization model could play a pivotal role in improving the response of health systems.


title: Back to basics: hand hygiene and isolation

text: PURPOSE OF REVIEW: Hand hygiene and isolation are basic, but very effective, means of preventing the spread of pathogens in healthcare. Although the principle may be straightforward, this review highlights some of the controversies regarding the implementation and efficacy of these interventions. RECENT FINDINGS: Hand hygiene compliance is an accepted measure of quality and safety in many countries. The evidence for the efficacy of hand hygiene in directly reducing rates of hospital-acquired infections has strengthened in recent years, particularly in terms of reduced rates of staphylococcal sepsis. Defining the key components of effective implementation strategies and the ideal method(s) of assessing hand hygiene compliance are dependent on a range of factors associated with the healthcare system. Although patient isolation continues to be an important strategy, particularly in outbreaks, it also has some limitations and can be associated with negative effects. Recent detailed molecular epidemiology studies of key healthcare-acquired pathogens have questioned the true efficacy of isolation, alone as an effective method for the routine prevention of disease transmission. SUMMARY: Hand hygiene and isolation are key components of basic infection control. Recent insights into the benefits, limitations and even adverse effects of these interventions are important for their optimal implementation.


title: Cardiac Injury and COVID-19: A Systematic Review and Meta-Analysis

text: BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, a link between acute cardiac injury and COVID-19 infection has been observed. There is currently no consensus on the incidence of cardiac injury, its relationship to prognosis, or its possible cause. This article provides a comprehensive review and meta-analysis of the incidence, comorbidities, outcomes and possible mechanisms of acute cardiac injury in COVID-19 patients. METHODS: We searched PubMed and Embase for studies that evaluated cardiac injury in hospitalized COVID-19 patients. Demographic information, co-morbidities, and relevant laboratory values were extracted and a meta-analysis was performed. RESULTS: Sixteen studies from China, Italy and the US with 2224 patients were included in this meta-analysis. The incidence of cardiac injury was 24.4% (542/2224 patients) in hospitalized COVID-19 patients. The all-cause mortality in patients with cardiac injury was 72.6% (OR=17.32, 95% CI 9.21-32.57) compared to those without cardiac injury (14.5%). In subgroup analyses, factors associated with increased risk of developing cardiac injury were older age and history of hypertension (HTN), and chronic obstructive respiratory disease (COPD). CONCLUSION: Cardiac injury is common in hospitalized COVID-19 patients and is significantly associated with mortality. Patients who were older with HTN and COPD were prone to develop cardiac injury. Early screening, triage and cardiac monitoring are recommended for these patients.


Real-Time Smart Patient Monitoring and Assessment Amid COVID-19 Pandemic – an Alternative Approach to Remote Monitoring


title: Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism

text: The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.


title: Catastrophe évolutive, quelle pourrait-être l’influence des conditions météorologiques sur l’évolution de la pandémie CoViD-19?

text: Résumé Une des préoccupations classiques de la gestion des catastrophes est d’en connaître l’évolutivité. Quelle est celle de la CoViD-19? Un questionnaire a été adressé à des confrères de 14 pays situés dans la zone chaude intertropicale pour établir une comparaison avec deux pays tempérés. Nous avons pu disposer des cas relevés et des conditions météorologiques de six îles françaises et de six pays africains francophones pour lesquels les mesures barrières gouvernementales ont été identiques à celles prises en Italie et en France. Le rôle positif de la température qui diminue la diffusion de la CoViD-19 et sa létalité a pu être mis en évidence. Dans les îles tropicales françaises, les cas importés (avions, bateaux) ont représenté en moyenne 33% de la totalité des cas sans influence sur la propagation virale, restée faible. La saisonnalité de la CoViD-19 doit faire craindre son retour à l’entrée de l’hiver et inciter à mieux préparer personnels et moyens. Summary One of the classic factors in disaster management is knowing its scalability. What is it in the case of CoViD-19? A questionnaire was sent to our colleagues from 14 countries located in the intertropical hot zone to establish a comparison with two temperate countries. We were able to collect the recorded cases and weather conditions from six French islands and six French-speaking African countries for which the government barrier measures were identical to those taken in Italy and France. We highlighted the positive role of temperature, which decreases the diffusion and the lethality of CoViD-19. In the French tropical islands, imported cases (by air, ships) represented a large percentage of cases (33% on average) which had no influence on the viral spread, which remained low. The seasonality of CoViD-19 should raise concern for its return at the start of winter and encourage better preparation of personnel and resources.


title: The impact of genomics on public health practice

text: INTRODUCTION: Genomic science is developing rapidly, and engagement of public health professionals will be necessary to appraise new technologies and use them effectively. SOURCES OF DATA: We use established domains of public health and draw on the literature and expert knowledge to illustrate how genomic technologies give rise to new applications. AREAS OF AGREEMENT: Genomic technologies are useful in rare inherited disease, including population screening programmes, in health care and for surveillance, diagnosis and treatment of infectious disease. AREAS OF CONTROVERSY: It is less clear when and how genetic susceptibility testing will be used for common chronic disease prevention or protection from environmental hazards. GROWING POINTS: Developments in public health practice will be necessary to ensure rapid and effective implementation of genomic science. AREAS TIMELY FOR DEVELOPING RESEARCH: Public health researchers should address how to accelerate the implementation of genomics for health benefit in developed and developing countries.


title: Detection of SARS-CoV-2 is comparable in clinical samples preserved in saline or viral transport media

text: As the COVID-19 pandemic sweeps across the world, the availability of viral transport media (VTM) has become severely limited, contributing to delays in diagnosis and rationing of diagnostic testing. Given that SARS-CoV-2 viral RNA has demonstrated stability, we posited that phosphate buffered saline (PBS) may be a viable transport medium, as an alternative to VTM), for clinical qPCR testing. We assessed the intra- and inter-individual reliability of SARS-CoV-2 qPCR in clinical endotracheal secretion samples transported in VTM or PBS, evaluating the stability of the RT-qPCR signal for three viral targets (N gene, ORF1ab, and S gene) when samples were stored in these media at room temperature for up to 18 hours. We report that using PBS as a transport medium has high intra-and inter-individual reliability, maintains viral stability, and is comparable to VTM in the detection of the three SARS-CoV-2 genes through 18 hours of storage. Our study establishes PBS as a clinically useful medium that can be readily deployed for transporting and short-term preservation of specimens containing SARS-CoV-2. Use of PBS as a transport medium has the potential to increase testing capacity for SARS-CoV-2, aiding more widespread screening and early diagnosis of COVID-19.


title: Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus

text: BACKGROUND: Coronaviruses are an important cause of infectious diseases in humans, including severe acute respiratory syndrome (SARS), and have the continued potential for emergence from animal species. A major factor in the host range of a coronavirus is its receptor utilization on host cells. In many cases, coronavirus-receptor interactions are well understood. However, a notable exception is the receptor utilization by group 3 coronaviruses, including avian infectious bronchitis virus (IBV). Feline aminopeptidase N (fAPN) serves as a functional receptor for most group 1 coronaviruses including feline infectious peritonitis virus (FIPV), canine coronavirus, transmissible gastroenteritis virus (TGEV), and human coronavirus 229E (HCoV-229E). A recent report has also suggested a role for fAPN during IBV entry (Miguel B, Pharr GT, Wang C: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002, 147:2047–2056. RESULTS: Here we show that, whereas both transient transfection and constitutive expression of fAPN on BHK-21 cells can rescue FIPV and TGEV infection in non-permissive BHK cells, fAPN expression does not rescue infection by the prototype IBV strain Mass41. To account for the previous suggestion that fAPN could serve as an IBV receptor, we show that feline cells can be infected with the prototype strain of IBV (Mass 41), but with low susceptibility compared to primary chick kidney cells. We also show that BHK-21 cells are slightly susceptible to certain IBV strains, including Ark99, Ark_DPI, CA99, and Iowa97 (<0.01% efficiency), but this level of infection is not increased by fAPN expression. CONCLUSION: We conclude that fAPN is not a functional receptor for IBV, the identity of which is currently under investigation.


title: Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer

text: Summary Background Scirrhous gastric cancer is associated with peritoneal dissemination and advanced lymph node metastasis from an early stage, and the prognosis is still poor. In this study, we aimed to analyze candidate molecules for targeted therapy of scirrhous gastric cancer. We searched for molecules/metabolic activity that might be predominantly expressed in a subpopulation of scirrhous gastric cancer cells and might function as cancer stem cell markers. Results For this purpose, we investigated the expression of various cell surface markers and of aldehyde dehydrogenase (ALDH) activity. These analyses showed that the scirrhous gastric cancer cell lines HSC-58 and HSC-44PE heterogeneously expressed CD13, while CD44, CDCP1, EpCAM and ABCG2 were expressed uniformly. Moreover, 10% of the total HSC-58 cell population expressed ALDH enzyme activity. A subpopulation of cells strongly positive for ALDH also expressed high levels of CD13, both of which are known as cancer stem cell markers. HSC-58 cells expressing high levels of CD13 showed lower sensitivity to a cancer drug cisplatin than cells with low levels of CD13. In contrast, CD13-high subpopulation of HSC-58 was more sensitive to an aminopeptidase N inhibitor bestatin. In terms of antibody-drug therapy, anti-CD13-immunotoxin was highly cytotoxic towards HSC-58 cells and was more cytotoxic than anti-EpCAM-immunotoxin. Conclusion These data suggest that CD13 is a suitable cell surface candidate for targeted antibody-drug therapy of scirrhous gastric cancer.


title: Fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance (EMARIS) network and first scientific conference on acute respiratory infections in the Eastern Mediterranean Region, 11–14 December, 2017, Amman, Jordan

text: Abstract Influenza causes significant morbidity and mortality worldwide. Owing to its ability to rapidly evolve and spread, the influenza virus is of global public health importance. Information on the burden, seasonality and risk factors of influenza in countries of the World Health Organization Eastern Mediterranean Region is emerging because of collaborative efforts between countries, WHO and its partners over the past 10 years. The fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance network was held in Amman, Jordan on 11–14 December 2017. The meeting reviewed the progress and achievements reported by the countries in the areas of surveillance of and response to seasonal, zoonotic and pandemic influenza. The first scientific conference on acute respiratory infection in the Eastern Mediterranean Region was held at the same time and 38 abstracts from young researchers across the Region were presented on epidemiological and virological surveillance, outbreak detection and response, influenza at the animal-human interface, use and efficacy of new vaccines to control respiratory diseases and pandemic influenza threats. The meeting identified a number of challenges and ways to improve the quality of the surveillance system for influenza, sustain the system so as to address pandemic threats and use the data generated from the surveillance system to inform decision-making, policies and practices to reduce the burden of influenza-associated illnesses in the Region.


title: Covid-19’s Impact on Supply Chain Decisions: Strategic Insights for NASDAQ 100 Firms using Twitter Data

text: The coronavirus pandemic is having a clear impact on the supply chains of virtually all manufacturers, retailers, and wholesalers. As the world attempts to navigate through this difficult time, most companies are struggling to maintain a steady flow of required goods and services. Whether it is frozen foods and grocery items (i.e., toilet papers), or ventilators and masks, or even the services (i.e., clinic visits), the supply chain has been facing multiple obstacles. Most models and frameworks built in the extant literature are not been able to capture these disruptions and as such, firms are not having proper strategies to deal with. For firms with complex supply chains (i.e., manufacturing, retailing), it is indeed critical to identify strategies to deal with such a crisis. In this paper, we intend to offer strategic insights in terms of major issues firms are facing and strategic options firms are contemplating. We rely on the twitter data for NASDAQ 100 firms to generate themes regarding the issues faced by the firms and the strategies they are adopting using text analytics tools. We find that firms are facing challenges in terms of demand-supply mismatch, technology, development of a resilient supply chain. Moreover, moving beyond profitability, firms are experiencing difficulties to construct a sustainable supply chain. We provide futuristic strategic recommendations for the rebuilding of the supply chain.


title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain

text: Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.


title: COVID-19 in otolaryngologist practice: a review of current knowledge

text: PURPOSE: Otorhinolaryngological manifestations are common symptoms of COVID-19. This study provides a brief and precise review of the current knowledge regarding COVID-19, including disease transmission, clinical characteristics, diagnosis, and potential treatment. The article focused on COVID-19-related information useful in otolaryngologist practice. METHODS: The Medline and Web of Science databases were searched without a time limit using terms “COVID-19”, “SARS-CoV-2” in conjunction with “otorhinolaryngological manifestation”, “ENT”, and “olfaction”. RESULTS: The most common otolaryngological dysfunctions of COVID-19 were cough, sore throat, and dyspnea. Rhinorrhea, nasal congestion and dizziness were also present. COVID-19 could manifest as an isolated sudden hyposmia/anosmia. Upper respiratory tract (URT) symptoms were commonly observed in younger patients and usually appeared initially. They could be present even before the molecular confirmation of SARS-CoV-2. Otolaryngologists are of great risk of becoming infected with SARS-CoV-2 as they cope with URT. ENT surgeons could be easily infected by SARS-CoV-2 during performing surgery in COVID-19 patients. CONCLUSION: Ear, nose and throat (ENT) symptoms may precede the development of severe COVID-19. During COVID-19 pandemic, patients with cough, sore throat, dyspnea, hyposmia/anosmia and a history of travel to the region with confirmed COVID-19 patients, should be considered as potential COVID-19 cases. An otolaryngologist should wear FFP3/N95 mask, glasses, disposable and fluid resistant gloves and gown while examining such individuals. Not urgent ENT surgeries should be postponed. Additional studies analyzing why some patients develop ENT symptoms during COVID-19 and others do not are needed. Further research is needed to determine the mechanism leading to anosmia.


title: Biological characterization and pathogenicity of a newly isolated Chinese highly virulent genotype GIIa porcine epidemic diarrhea virus strain

text: Since 2010, continual outbreaks of highly virulent variants of porcine epidemic diarrhea virus (PEDV) belonging to genotype GII have led to serious economic losses for the Chinese swine industry. To better understand the biological characteristics and pathogenicity of the current prevalent Chinese PEDV field strains, in this study, a highly virulent Chinese genotype GIIa PEDV strain, CH/HBXT/2018, was isolated and serially propagated using Vero cells. Sequencing and phylogenetic analysis showed that strain CH/HBXT/2018 contained novel insertion and deletion mutations in the S gene region relative to the classical strain and belonged to the genotype GIIa, similar to other recently isolated PEDV strains from China and the United States. Pig infection studies indicated that the CH/HBXT/2018 strain was highly virulent in suckling piglets, and the median pig diarrhea dose (PDD(50)) was 8.63 log(10)PDD(50)/3 mL at 7 days postinfection (DPI). The results of the present study are important for future PEDV challenge studies and the development of new PEDV vaccines based on prevalent field strains for the prevention and control of PED in China.


title: Communicating science in a crisis

text: The global COVID-19 pandemic is a challenge for health systems and for science communication. To protect public health, science had to obtain knowledge about the new disease at record speed and efficiently communicate it to political leaders, health professionals and the public. Communication failures and the rise of misinformation have cost lives.