title: Discovery of a novel swine enteric alphacoronavirus (SeACoV) in southern China

text: Abstract Outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), have been recorded in a pig farm in southern China since February 2017. Isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named SeACoV) related to the bat coronavirus HKU2 identified in the same region a decade ago. Specific fluorescence signal was detected in Vero cells infected with SeACoV by using a positive sow serum collected in the same farm, but not by using TGEV-, PEDV- or PDCoV-specific antibody. Electron microscopy observation demonstrated that the virus particle with surface projections was 100–120nm in diameter. Complete genomic sequencing and analyses of SeACoV indicated that the extreme amino-terminal domain of the SeACoV spike (S) glycoprotein structurally similar to the domain 0 of the alphacoronavirus NL63, whereas the rest part of S structurally resembles domains B to D of the betacoronavirus. The SeACoV-S domain 0 associated with enteric tropism had an extremely high variability, harboring 75-amino-acid (aa) substitutions and a 2-aa insertion, compared to that of HKU2, which is likely responsible for the extended host range or cross-species transmission. The isolated virus was infectious in pigs when inoculated orally into 3-day-old newborn piglets, leading to clinical signs of diarrhea and fecal virus shedding. These results confirmed that it is a novel swine enteric coronavirus representing the fifth porcine coronavirus.


COVID‐19: its impact on dental schools in Italy, clinical problems in endodontic therapy and general considerations


title: A Brief Telephone Severity Scoring System and Therapeutic Living Centers Solved Acute Hospital-Bed Shortage during the COVID-19 Outbreak in Daegu, Korea

text: With the epidemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2, the number of infected patients was rapidly increasing in Daegu, Korea. With a maximum of 741 new patients per day in the city as of February 29, 2020, hospital-bed shortage was a great challenge to the local healthcare system. We developed and applied a remote brief severity scoring system, administered by telephone for assigning priority for hospitalization and arranging for facility isolation (“therapeutic living centers”) for the patients starting on February 29, 2020. Fifteen centers were operated for the 3,033 admissions to the COVID-19 therapeutic living centers. Only 81 cases (2.67%) were transferred to hospitals after facility isolation. We think that this brief severity scoring system for COVID-19 worked safely to solve the hospital-bed shortage. Telephone scoring of the severity of disease and therapeutic living centers could be very useful in overcoming the shortage of hospital-beds that occurs during outbreaks of infectious diseases.


Pakistanis’ Mental Health during the COVID-19


title: Predicting geographic location from genetic variation with deep neural networks

text: Most organisms are more closely related to nearby than distant members of their species, creating spatial autocorrelations in genetic data. This allows us to predict the location of origin of a genetic sample by comparing it to a set of samples of known geographic origin. Here, we describe a deep learning method, which we call Locator, to accomplish this task faster and more accurately than existing approaches. In simulations, Locator infers sample location to within 4.1 generations of dispersal and runs at least an order of magnitude faster than a recent model-based approach. We leverage Locator’s computational efficiency to predict locations separately in windows across the genome, which allows us to both quantify uncertainty and describe the mosaic ancestry and patterns of geographic mixing that characterize many populations. Applied to whole-genome sequence data from Plasmodium parasites, Anopheles mosquitoes, and global human populations, this approach yields median test errors of 16.9km, 5.7km, and 85km, respectively.


title: Pandemie- und Seuchengeschichte als Pflegegeschichte?

text: This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. In the current COVID 19 pandemic, the importance of professional nursing is widely recognized. In German-speaking and international research, the history of nursing during pandemics and epidemics is largely unwritten. This paper gives an overview of questions and results in this research area and discusses the potential of a pandemic nursing history.


title: Assessing health burden risk and control effect on dengue fever infection in the southern region of Taiwan

text: BACKGROUND: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. OBJECTIVES: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. MATERIALS AND METHODS: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R(0))–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. RESULTS: We showed that R(0) and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323 (267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. CONCLUSION: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan.


title: Acute Enteritis or Gastroenteritis in Young Dogs as a Predisposing Factor for Intestinal Intussusception: a Retrospective Study

text: Various types of intestinal intussusception were diagnosed in 29 of 220 young dogs with acute enteritis or gastroenteritis, due to canine parvovirus (85 cases) or presumably to other infectious agents, inflammation or less common hypermotility and metabolic derangements (135 cases). As the other causes of the disease were excluded, acute enteritis or gastroenteritis was considered to be the most likely predisposing factor for the intestinal intussusception. The most common type of intussusception was found to be the ileocolic. Of the 21 dogs that underwent surgical resection and anastomosis of the intestine, 18 dogs recovered completely and three died due to complications. The high survival rate was due to the effective pre‐operative, surgical and post‐operative therapy.


title: Adult outpatient experience of the 2009 H1N1 pandemic: Clinical course, pathogens, and evaluation of case definitions

text: Summary Objectives The aim was to describe causative agents and clinical characteristics in adult outpatients with upper airway symptoms during the 2009 H1N1 pandemic and to evaluate case definitions that are used in clinical practice. Methods From August through December 2009, 964 symptomatic adult outpatients were included. RT-PCR was used to detect the following pathogens: influenza A (H1N1) and B, parainfluenza 1–4, adenovirus, respiratory syncytial virus, human rhinovirus, human metapneumovirus, human coronavirus (OC43, 229E, NL63), Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella species. The Dutch GHOR, American CDC and WHO, and British HPA case definitions were evaluated. Results A respiratory pathogen was detected in 41% of tested patient samples; influenza A (H1N1) and human rhinovirus were both detected in 16%. Clinical presentation of influenza cases was significantly more serious when compared to rhinovirus or negative-tested cases. Test characteristics were almost similar for all 4 case definitions, with an average sensitivity of 66%, specificity of 70%, positive predictive value of 34% and negative predictive value of 90%. Conclusions Influenza A (H1N1) and human rhinovirus were the major pathogens responsible for respiratory disease. The 2009 H1N1 pandemic in Amsterdam followed a mild course. Test characteristics of 4 different clinical case definitions seemed comparable but rather useless.


title: Research progress on theaflavins: efficacy, formation, and preparation

text: Background: Theaflavins (TFs) are a category of natural compounds characterized with the benzotropolone skeleton. The prominent benefits of TFs have been well documented. Amount of research were conducted and excellent achievements were disclosed during the past years. However, as far as we know, there is no comprehensive review about TFs. Scope and approach: This review summarized the recent research progress. The activity of TFs on anti-oxidation, anti-mutagenicity, hypolipidemic, anti-inflammatory, anti-cancer, anti-viral effect as well as the epidemiological cure were sorted. Converging pioneer literature and deduction, the underlying formation mechanism of TFs was proposed. Subsequently, acquisition of TFs was pointed out to be the fundament for further research. Accelerated by enzyme, bio-synthesis of TFs were reviewed simultaneously. At the end, employing modern analysis instrument and technology, isolations of TFs were enumerated. Key findings and conclusions: Structure of the skeleton as well as functional groups were paramount related with the bio-activity of TFs. Meanwhile, oxidation pathway of two catechin molecules to form TFs were hypothesized. Also, ascertainment of the several therapeutic efficiency of the family members of TFs would be the next step in the future.


title: Development and biochemical and immunological characterization of early passage and immortalized bovine intestinal epithelial cell lines from the ileum of a young calf

text: The intestinal epithelium is a major site of interaction with pathogens. In bovine intestinal epithelial cells (BIECs), Toll-like receptors (TLRs) play an important role in innate immune responses against enteric pathogens. This study is aimed at establishing a stable bovine intestinal epithelial cell line that can be maintained by a continuous passage so that studies on innate immune responses against various enteric pathogens can be performed. The main goal was to establish pure cultures of primary and immortalized bovine intestinal epithelial cells from the ileum and then characterize them biochemically and immunologically. Mixed epithelial and fibroblast bovine ileal intestinal cultures were first established from a 2-day old calf. Limiting dilution method was used to obtain a clone of epithelial cells which was characterized using immunocytochemistry (ICC). The selected clone BIEC-c4 was cytokeratin positive and expressed low levels of vimentin, confirming the epithelial cell phenotype. Early passage BIEC-c4 cells were transfected with either simian virus 40 (SV40) large T antigen or human telomerase reverse transcriptase (hTERT), or human papillomavirus (HPV) type 16E6/E7 genes to establish three immortalized BIEC cell lines. The expression of SV40, hTERT and HPV E6/E7 genes in immortalized BIECs was confirmed by a polymerase chain reaction (PCR). Immunocytochemistry and immunofluorescence assays also confirmed the expression of SV40, hTERT and HPV E6 proteins. The immortalized BIECs were cytokeratin positive and all except HPV-BIECs expressed low levels of vimentin. A growth kinetics study indicated that there were no significant differences in the doubling time of immortalized BIECs as compared to early passage BIEC-c4 cells. All four BIEC types expressed TLR 1-10 genes, with TLR 3 and 4 showing higher expression across all cell types. These newly established early passage and immortalized BIEC cell lines should serve as a good model for studying infectivity, pathogenesis and innate immune responses against enteric pathogens.


title: Synbiotics suppress the release of lactate dehydrogenase, promote non‐specific immunity and integrity of jejunum mucosa in piglets

text: The aim of our experiment was to study how synbiotics are able to deal with the problems of post‐weaning piglets. Lactobacillus plantarum – Biocenol(TM) LP96 (CCM 7512), Lactobacillus fermentum – Biocenol(TM) LF99 (CCM 7514) and flaxseed (rich in n‐3 polyunsaturated fatty acids) were administered to 36 conventional piglets from a problematic breed with confirmed presence of enterotoxigenic Escherichia coli and Coronavirus. The experimental piglets were supplied with probiotic cheeses and crushed flax‐seed in the period starting 10 days before weaning and lasting up to 14 days post‐weaning. Piglets in the control group were supplied only control cheese. The impact of such additives on the release of lactate dehydrogenase (LDH; spectroscopic and electrophoretic assay), alteration of immunity (index of metabolic activity), jejunum histology (light microscopy), and health of conventional piglets from a problematic breed (monitoring of hematology, consistency and moisture of feces and body temperature) were examined. We found significant decrease in LDH leakage in the blood serum and tissue extracts, indicating better cell membrane integrity in the individual organs of animals. Probiotics and flaxseed applied together seem to be a good source of nutrients to improve the immune status and the integrity of jejunum mucosa during infection. © 2015 Japanese Society of Animal Science


title: A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress

text: INTRODUCTION: The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity METHODS: A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. RESULTS: There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (≤90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100% CONCLUSION: This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions.


title: Susceptibility of different eukaryotic cell lines to SARS-coronavirus

text: In order to define and characterize target cells of SARS-coronavirus (SARS-CoV) we studied the susceptibility of 23 different permanent and primary eukaryotic cell lines to SARS-coronavirus. Beneath Vero E6 cells SARS- Coronavirus infection could also be demonstrated in two pig cell lines (POEK, PS) and one human cell line (Huh-7) using the indirect immunofluorescence assay and a newly established quantitative real-time PCR. In all susceptible cell lines mRNA of the Angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV infection, could be detected by RT-PCR. Our results show that there is a correlation between the abundance of ACE2 mRNA and SARS-CoV susceptibility.


title: A Specially Designed Medical Screen for Children Suffering from Burns: A Randomized Trial of a Distraction-type Therapy

text: Abstract Objective To evaluate the impact of the specially designed medical dressing screen during wound dressing changes of children who suffered burns to their hand or foot. Design Randomized controlled trial. Setting Burns and Plastic Reconstruction Unit. Participants Children (N=120) with burns on up to 1%-5% of the total body surface area. Interventions The patients were selected and randomly allocated to 3 equal-sized groups as follows:control group (N=40): the children received only regular dressing changes; computer group (N=40): a touch-screen computer was used for children during dressing changes; medical screen group (N=40): a medical screen combined with the touch-screen computer were used for children during dressing changes. All patients underwent a dressing change once per day for four days. Data were distributed four times: immediately after the initial dressing change (T1); and immediately after each times at next three consecutive days (T2-T4). Main Outcome Measures The Pain level of the children evaluated by medical staffs was the primary outcome, the Pain level of the children evaluated by children's parents and the satisfaction of wound therapist were used as second outcomes. Results The mean scores related to pain level at the medical screen group displayed significantly better results than those of control group and those of the computer group. Additionally, the results of the pain evaluated by parents and satisfaction score of the wound therapist at the medical screen group was also better than other groups. Conclusions This study demonstrated “that the” application of the medical screen for burns can relieve the pain of 1-3 years old children suffering from a burns during dressing changes. Additionally, the application of the medical screen also increased the satisfaction of the parents and the wound therapist performing the dressing changes.


title: Dental student writes A Message from Corona for kids

text: Charity Tedder, 25, a final year dental student from Peninsula School of Dentistry, has written an e-book called A Message from Corona to help inform and reassure children during the COVID-19 pandemic The book, illustrated by Kent-based artist Leighton Noyes, explains vividly and engagingly how the virus has travelled around the world, and why hand-washing, social distancing and lockdown are so vital It can be read to children as young as age three to four or self-read by ages seven to eight and above There are also activity pages for children to help keep them engaged


title: Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death

text: Abstract Background An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella. Objectives To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death. Study design Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology. Results Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6×107 and 1.9×105 genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues. Conclusions This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death.


title: Improving knowledge and compliance with infection control Standard Precautions among undergraduate nursing students in Jordan

text: INTRODUCTION: The recent emergence and reemergence of infectious diseases have made the knowledge and practice of standard infection control precautions in developing countries more important than ever. However, schools of nursing in Jordan do not have a prescribed curriculum in Standard Precautions. PURPOSE: To test the effectiveness of using of an online education module and a learning contract on knowledge and compliance with infection control Standard Precautions among undergraduate nursing students in Jordan. METHODS: A sample of 256 undergraduate nursing students participated in an online education module in infection control Standard Precautions. A pretest–posttest design tested effectiveness using an online questionnaire (Questionnaires for Knowledge and Compliance with Standard Precautions) before and after the online instruction. RESULTS: Initially, subjects reported low levels of knowledge and compliance with Standard Precaution practices and relatively few (15.2%) had high scores. Compliance with Standard Precautions was somewhat better (27%). Significant differences in the mean scores of knowledge and compliance between pretest and posttest were found. CONCLUSION: Online instruction offers a consistent and effective method to include Standard Precautions into nursing education. Organizations that oversee nursing in Jordan have the option to strengthen all nursing curricula by mandating a standardized infection control curricula across all schools of nursing.


Sweet frequency: Implantable glucose sensor transmits data wirelessly


title: Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56 °C damages its genome integrity seriously

text: 2019-Novel Coronavirus (2019-nCoV) is the pathogen of Corona Virus Disease 2019. Nucleic acid detection of 2019-nCoV is one of the key indicators for clinical diagnosis. However, the positive rate is only 30-50%. Currently, fluorescent quantitative RT-PCR technology is mainly used to detect 2019-nCoV. According to “The Laboratory Technical Guidelines for Detection 2019-nCoV (Fourth Edition)” issued by National Health and Commission of China and “The Experts’ Consensus on Nucleic Acid Detection of 2019-nCoV” released by Chinese Society of Laboratory Medicine, the human samples must be placed under 56°C or higher to inactivate the viruses in order to keep the inspectors from virus infection before the nucleic acids were isolated as the template of qRT-PCR. In this study, we demonstrated that the virus inactivation treatment disrupts its genome integrity seriously when using porcine epidemic diarrhea virus (vaccine), a kind of coronavirus, as a model. Our results showed that only 50.11% of the detectable viral templates left after the inactivation of 56 °C for 30 minutes and only 3.36% left after the inactivation of 92 °C for 5 minutes when the samples were preserved by Hank’s solution, one of an isotonic salt solutions currently suggested. However, the detectable templates of viral nucleic acids can be unchanged after the samples were incubated at 56 °C or higher if the samples were preserved with an optimized solution to protect the RNA from being disrupted. We therefore highly recommend to carry out systematic investigation on the impact of high temperature inactivation on the integrity of 2019-nCoV genome and develop a sample preservation solution to protect the detectable templates of 2019-nCoV nucleic acids from high temperature inactivation damage.


title: Effects of Mutagenesis of Murine Hepatitis Virus NSP1 and NSP14 on Replication in Culture

text: For nsp1, the fact that the carboxy-terminal but not the amino-terminal half of the protein can be deleted suggests that there may be specific and distinct domains within the protein or that the entire protein is dispensable but that the RNA encoding the amino-terminal half of nsp1 cannot be deleted. The identification of specific required residues support the conclusion that it is the portion of the protein that is required for replication. The results of mutagenesis of the nsp14 coding region and flanking cleavage sites also provided important new insights into this protein and its requirements. Our previous study raised the question as to the essential nature of nsp14 in replication. The results of this study show that putative active site residues cannot be substituted without loss of replication in culture. Interestingly, mutagenesis of Tyr414 showed that while this residue can tolerate a number of substitutions, it was intolerant of Lysine or deletion. The results suggest that nsp14 is required for replication. However, whatever functions nsp14 serves appear to be retained by noncleaved or partially processed nsp14, since abolition of either the amino-terminal or carboxy-terminal cleavage site allowed recovery of viable virus.


title: Neonatal Mortality, Vesicular Lesions and Lameness Associated with Senecavirus A in a U.S. Sow Farm

text: A 300‐sow farrow‐to‐finish swine operation in the United States experienced a sudden and severe increase in mortality in neonatal piglets with high morbidity followed by vesicular lesions on the snout and feet of adult females and males. Affected live piglets were submitted for diagnostic investigation. Samples tested polymerase chain reaction (PCR) negative for foot‐and‐mouth disease virus, porcine delta coronavirus, porcine epidemic diarrhoea virus, porcine rotavirus types A, B and C, transmissible gastroenteritis virus, and porcine reproductive and respiratory syndrome virus. Senecavirus A (SV‐A) formerly known as Seneca Valley virus was detected by real‐time reverse‐transcription polymerase chain reaction (rRT‐PCR) from serum, skin and faeces of piglets and from serum and faeces of sows. SV‐A was isolated in cell culture from piglet samples. SV‐A VP1 gene region sequencing from piglet tissues was also successful. A biosecurity and disease entry evaluation was conducted and identified potential biosecurity risks factors for the entry of new pathogens into the operation. This is the first case report in the United States associating SV‐A with a clinical course of severe but transient neonatal morbidity and mortality followed by vesicular lesions in breeding stock animals. Veterinarians and animal caretakers must remain vigilant for vesicular foreign animal diseases and report suspicious clinical signs and lesions to state animal health authorities for diagnostic testing and further investigation.


Strategies for patient with cancer during COVID‐19 pandemic


title: L’union sacrée entre l’hôpital public et le privé face à la pandémie COVID-19 : un exemple régional

text: Résumé En tant que médecin anesthésiste exerçant en secteur libéral, nous souhaitons faire part de notre expérience et de notre vécu face à la pandémie Covid-19. Notre région et notre ville (Amiens) a été une des plus touchée en France et nous avons dû faire face à un afflux massif de victimes du Covid-19 avec insuffisance respiratoire aiguë. Face à une saturation des lits de réanimation du CHU, une organisation régionale s’est rapidement mise en place. A travers cette correspondance, nous faisons part de notre expérience d’organisation au plan régional avec création d’une unité de réanimation au sein d’une structure privée, main dans la main avec nos confrères de réanimation du CHU. Nous souhaitons mettre en avant ici « l’union sacré » qui s’est développé entre les deux structures et qui est, selon nous un élément important de notre spécialité.


Cardiovascular Consequences and Considerations of Coronavirus Infection – Perspectives for the Cardiothoracic Anesthesiologist and Intensivist During the Coronavirus Crisis


Total Distance and Radius of Wandering of Patients with COVID19 before the First Final Diagnosis: GPS Tracking Analysis


title: Positive Immunolabelling for Feline Infectious Peritonitis in an African Lion (Panthera leo) with Bilateral Panuveitis

text: Summary A 15-year-old male African lion (Panthera leo) was presented with blindness due to bilateral panuveitis with retinal detachment. Feline coronavirus (FCoV) antigen was identified immunohistochemically in ocular macrophages, consistent with a diagnosis of feline infectious peritonitis (FIP) infection. This is the first report of FIP in an African lion and the first report of ocular FIP in a non-domestic felid.


Tests sériques et déconfinement progressif


title: Manipulation of autophagy by (+) RNA viruses

text: Abstract Autophagy is an evolutionarily conserved process central to host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.


title: The Role of the Traveler in Emerging Infections and Magnitude of Travel

text: Travel and trade have grown immensely. Travelers interact with people and microbes during their journeys, and can introduce infectious agents to new areas and populations. Studying illnesses in travelers is a source of knowledge into diseases of resource-poor regions and the control of these diseases. Travel-associated illnesses also serve to detect emerging infections.


title: Development of Drugs Based on High-Polymeric Double-Stranded RNA for Antiviral and Antitumor Therapy

text: Abstract—The review summarizes literature data on the development of drugs based on natural and synthetic high-polymeric double-stranded RNA (dsRNA), their antiviral, immunoadjuvant, and antitumor properties. Special attention is paid to cell receptors responding to exogenous dsRNA, pathways of dsRNA-dependent antiviral reaction, ability of dsRNA to inhibit growth and induce apoptosis of malignant cells. It has been shown that enhancing the innate immune response with dsRNA can be an effective component in improving methods for treating and preventing infectious and cancer diseases. The further use of dsRNA for the correction of pathological processes of different origin is discussed.


title: Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004

text: Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years.


title: An evolving crisis

text: Insights into how viruses change over time can help us cope with this pandemic and avoid future ones, says Jonathan R. Goodman


title: The case for Chronotherapy in COVID‐19 induced Acute Respiratory Distress Syndrome (ARDS).

text: COVID‐19, the disease resulting from infection by a novel coronavirus: SARS‐Cov2 that has rapidly spread since November 2019 leading to a global pandemic. SARS‐Cov2 has infected over 4 million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of Acute Respiratory Distress Syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti‐inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS and thus chronotherapy may be used to effectively manage ARDS in COVID‐19 patients.


title: The social psychological impact of the COVID-19 pandemic on medical staff in China: A cross-sectional study

text: BACKGROUND. The COVID-19 outbreak required the significantly increased working time and intensity for health professionals in China, which may cause stress signs. METHODS. From March 2–13 of 2020, 4,618 health professionals in China were included in an anonymous, self-rated online survey regarding their concerns on exposure to the COVID-19 outbreak. The questionnaires consisted of five parts: basic demographic information and epidemiological exposure; occupational and psychological impact; concerns during the episode; coping strategies; and the Huaxi Emotional-Distress Index (HEI). RESULTS. About 24.2% of respondents experienced high levels of anxiety or/and depressive symptoms since the COVID-19 outbreak. Respondents who worried about their physical health and those who had COVID-19 infected friends or close relatives were more likely to have high HEI levels, than those without these characteristics. Further, family relationship was found to have an independent protective effect against high HEI levels. Their main concerns were that their families would not be cared for and that they would not be able to work properly. Compared to respondents with clear emotional problems, those with somewhat hidden emotional issues adopted more positive coping measures. CONCLUSIONS. About a quarter of medical staff experienced psychological problems during the pandemic of COVID-19. The psychological impact of stressful events was related to worrying about their physical health, having close COVID-19 infected acquaintances and family relationship issues. Therefore, the psychological supprot for medical staff fighting in the COVID-19 pandemic may be needed.


title: Cytomegalovirus enteritis in a premature infant

text: Abstract Background/Purpose: Up to 2.5% of newborn infants are cytomegalovirus (CMV) positive at birth. Five percent will be symptomatic at birth, including cytomegalic inclusion disease. Symptoms such as hearing loss and mental retardation will ultimately develop in 15%. Methods: The authors describe a case of CMV enteritis in a 2.2-kg newborn that presented as necrotizing enterocolitis (NEC) and subsequently developed a colonic stricture. Results: There are four reports of neonatal CMV enteritis in the nonEnglish-language literature. Cytomegalovirus enteritis has become prevalent among the immunosuppressed pediatric and adult patient population. Conclusions: We propose the addition of CMV to the list of pathogens responsible for NEC. A review of neonatal CMV infection is provided.


Schweres akutes respiratorisches Syndrom (SARS): Maßnahmen des öffentlichen Gesundheitswesens, um die Verbreitung während des Ausbruchs in Toronto zu kontrollieren


title: Isolation, genomic characterization, and pathogenicity of a Chinese porcine deltacoronavirus strain CHN-HN-2014

text: Abstract Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes diarrhea in piglets. Since the first outbreak of PDCoV in the United States in 2014, this novel porcine coronavirus has been detected in South Korea, Canada, Mexico, Thailand, and China. In this study, a Chinese PDCoV strain, designated CHN-HN-2014, was isolated from piglets with severe diarrhea on a pig farm in Henan Province, China, and examined with a specific immunofluorescence assay and electron microscopy. Genomic analysis showed that CHN-HN-2014 shares 91.6%–99.4% nucleotide identity with other known PDCoV strains. The pathogenicity of CHN-HN-2014 was further investigated in 5-day-old and 21-day-old piglets. Both kinds of piglets developed clear clinical symptoms, including vomiting, anorexia, lethargy, and severe diarrhea, by 2days postinoculation (DPI), and diarrhea persisted for about 5–6 days. Viral shedding was detected in rectal swabs until 14 DPI in challenged 5-day-old pigs and until 18 DPI in challenged 21-day-old pigs. At necropsy at 4 DPI, macroscopic and microscopic lesions were observed and viral antigen was detected in the small intestines with immunohistochemical staining. These data demonstrate that Chinese PDCoV strain CHN-HN-2014 shares high nucleotide identity with previously reported PDCoV strains and is pathogenic in 5-day-old and 21-day-old piglets.


title: Anticoagulation Options for Coronavirus Disease 2019 (COVID-19)-Induced Coagulopathy

text: As the coronavirus disease 2019 (COVID-19) pandemic is evolving, coagulopathy induced by the disease and its severe complications are raising concerns in the medical community. Because coagulopathy caused by COVID-19 has been difficult to control, it is important to have a better understanding of what therapies have been studied thus far and what therapies have demonstrated better outcomes for hospitalized patients. This review is focused on literature, research, and expert clinical judgments published in 2020 with a few references to articles published earlier. The review introduces the interim guidelines of the International Society of Thrombosis and Haemostasis (ISTH) for management of COVID-19-induced coagulopathy, discusses the efficacy of these guidelines in clinical settings, and summarizes the response of the scientific community to these guidelines and their clinical implications. Due to the failure of patients to respond to the prophylactic doses of heparin recommended by ISTH, higher doses of heparin may be necessary to achieve adequate anticoagulation. Patients’ resistance to prophylactic doses of heparin could be due to low levels of anti-thrombin and high levels of fibrinogen, which would reinforce the use of therapeutic doses of heparin in the early stages of hospitalization. The review also compares low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as anticoagulant choices for COVID-19 patients. Given the complications specific to COVID-19, UFH may be a better choice of anticoagulant. Outpatient anticoagulation options are also reviewed. Changing qualified patients from vitamin K antagonists (VKA) to direct-acting oral anticoagulant (DOAC) for the convenience of less frequent monitoring may be appropriate. New anticoagulant, nafamostat, used in Japan is also discussed as a possible potentiate for heparin therapy.


title: The paralyzed cat. Neuroanatomic diagnosis and specific spinal cord diseases

text: Practical relevance Neurological diagnosis in veterinary practice can be very cAlthough gait disturbance is one of the most common neurological presentations in feline medicine, the clinical approach to the paralyzed cat can be challenging. After excluding orthopedic and cardiovascular diseases that may mimic a neurological condition, the clinician has to address a long list of different diseases that may affect the spinal cord and produce paresis. Clinical challenges In many cases a definitive cause of spinal weakness in cats is difficult to prove. Even when treatable diseases are identified, the prognosis is very much dependent on the severity of the clinical signs and their chronicity. This review sets out to describe the specific approach, diagnosis and management of cats with spinal cord disease and to outline the most common diseases responsible. Patient group Patients of either gender and all ages and breeds can be affected by spinal cord disease. Evidence base Many diseases affecting the spinal cord of cats, which include fibrocartilaginous embolic myelopathy, intervertebral disc disease, exogenous spinal cord trauma, spinal cord lymphosarcoma and feline infectious peritonitis, are well described in the literature. Many of these descriptions, however, have been based on case reports or series. While there have been several retrospective studies that describe the characteristics and incidence of these diseases in cats, there are no long term treatment trials or outcome studies to assist with prognostic determinations.


title: Ubiquitin-based anticancer therapy: Carpet bombing with proteasome inhibitors vs surgical strikes with E1, E2, E3, or DUB inhibitors

text: Abstract The proteasome inhibitor bortezomib remains the only ubiquitin pathway effector to become a drug (VELCADE®) and has become a successful treatment for hematological malignancies. While producing a global cellular effect, proteasome inhibitors have not triggered the catastrophe articulated initially in terms such as “buildup of cellular garbage”. Proteasome inhibitors, in fact, do have a therapeutic window, although in the case of the prototype bortezomib it is small owing to peripheral neuropathy, myelosuppression and, as recently reported, cardiotoxicity [1]. Currently, several second-generation molecules are undergoing clinical evaluation to increase this window. An alternative strategy is to target ubiquitin pathway enzymes acting at non-proteasomal sites—E1, E2, and E3, associated with ubiquitin conjugation, and deubiquitylating enzymes (“DUBs”)—that act locally on selected targets rather than on the whole cell. Inhibitors (or activators, in some cases) of these enzymes should be developable as selective antitumor agents with toxicity profiles superior to that of bortezomib. Various therapeutic hypotheses follow from known cellular mechanisms of these target enzymes; most hypotheses relate to cancer, reminiscent of the FDA-approved protein kinase inhibitors now marketed. Since ubiquitin tagging controls the cellular content, activity, or compartmentation of proteins associated with disease, inhibitors or activators of ubiquitin conjugation or deconjugation are predicted to have an impact on disease. For practical and empirical reasons, inhibitors of ubiquitin pathway enzymes have been the favored therapeutic avenue. In approximately the time that has elapsed since the approval of bortezomib in 2003, there has been some progress in developing potential anticancer drugs that target various ubiquitin pathway enzymes. An E1 inhibitor and inhibitors of E3 are now in clinical trial, with some objective responses reported. Appropriate assays and/or rational design may uncover improved inhibitors of these enzymes, as well as E2 and DUBs, for further development. Presently, it should become clear whether one or both of the two general strategies for ubiquitin-based drug discovery will lead to truly superior new medicines for cancer and other diseases. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.


Ultrastructure of SARS-CoV, FIPV, and MHV Revealed by Electron Cryomicroscopy


Keep Healthcare Workers Safe: Application of Teleoperated Robot in Isolation Ward for COVID-19 Prevention and Control


Severe SARS-CoV-2 infection in critical care


title: Infection risks faced by public health laboratory services teams when handling specimens associated with COVID-19

text: Abstract Infection risks of handling specimens associated with SARS-CoV-2 by public health laboratory services teams were assessed to scrutinize the potential hazards arising from the work procedures. Through risk assessments of all work sequences, laboratory equipment and workplace environments, no aerosol-generating procedure could be identified except the procedures (mixing and transfer steps) inside biological safety cabinets. Appropriate personal protective equipment (PPE) such as surgical masks, protective gowns, face shields/safety goggles and disposable gloves, together with pertinent safety training were provided for laboratory work. Proper disinfection and good hand hygiene practices could minimize the probability of SARS-CoV-2 infection at work. All residual risk levels of the potential hazards identified were within the acceptable level. Contamination by gloved hands was considered as a major exposure route for SARS-CoV-2 when compared with eye protection equipment. Competence in proper donning and doffing of PPE accompanied by hand washing technique was of utmost importance for infection control.


title: Exosomes as Sentinels against Bacterial Pathogens

text: The ability of cells to form and release multiple classes of extracellular vesicles (EVs) is an increasingly well-recognized phenomenon. EVs are best known as mediators of intercellular communication. However, in a recent issue of Nature, Keller et al. show that they function as decoys to mitigate bacterial toxins.


title: Chapter 20 Design of genomic signatures for pathogen identification and characterization

text: Abstract Once the genome of a microbial organism has been sequenced, it becomes possible to utilize portions of the genome, known as “signatures” to identify when that organism is present in a complex clinical or environmental sample. Genomic signatures can be at multiple levels of resolution depending on the questions being asked. (“Is this white powder anthrax?”; “Does this white powder match any of the anthrax samples taken from every laboratory in the United States that possesses anthrax?”) Multiple technologies exist to turn abstract genomic signatures into assays that can interrogate complex samples with varying degrees of speed, sensitivity, specificity, and cost. The recent flood of microbial genomic data has complicated the task of designing genomic signatures.


title: The management of emergency spinal surgery during the COVID-19 pandemic in Italy: a preliminary report

text: AIMS: The current pandemic caused by COVID-19 is the biggest challenge for national health systems for a century. While most medical resources are allocated to treat COVID-19 patients, several non-COVID-19 medical emergencies still need to be treated, including vertebral fractures and spinal cord compression. The aim of this paper is to report the early experience and an organizational protocol for emergency spinal surgery currently being used in a large metropolitan area by an integrated team of orthopaedic surgeons and neurosurgeons. METHODS: An organizational model is presented based on case centralization in hub hospitals and early management of surgical cases to reduce hospital stay. Data from all the patients admitted for emergency spinal surgery from the beginning of the outbreak were prospectively collected and compared to data from patients admitted for the same reason in the same time span in the previous year, and treated by the same integrated team. RESULTS: A total of 19 patients (11 males and eight females, with a mean age of 49.9 years (14 to 83)) were admitted either for vertebral fracture or spinal cord compression in a 19-day period, compared to the ten admitted in the previous year. No COVID-19 patients were treated. The mean time between admission and surgery was 1.7 days, significantly lower than 6.8 days the previous year (p < 0.001). CONCLUSION: The structural organization and the management protocol we describe allowed us to reduce the time to surgery and ultimately hospital stay, thereby maximizing the already stretched medical resources available. We hope that our early experience can be of value to the medical communities that will soon be in the same emergency situation. Cite this article: Bone Joint J 2020;102-B(6):671–676.


title: Neuronal Angiotensin

text: Many tissues, including the brain, contain all components of the renin–angiotensin system and generate angiotensin peptides independent of the systemic, circulating system. Within the brain renin, some questions remain as to how the precursor, angiotensinogen, and its processing enzymes interact to produce the active compounds, angiotensin II/III, because they are rarely localized to the same brain nucleus let alone the same cell. These questions aside, there is clear evidence for actions of angiotensin peptides in regions behind the blood–brain barrier. Receptors for angiotensin peptides, including AT1 and AT2 receptors, are distributed in a characteristic pattern throughout the brain, with many of these sites behind the blood–brain barrier. Stimulation of these receptors affects multiple physiological functions – actions which often complement the physiological roles established for the systemic renin–angiotensin system. These include effects on fluid and electrolyte homeostasis, autonomic and neuroendocrine regulation, and modulation of sensory function. Moreover, administration of selective receptor antagonists attenuates several of these functions when they are activated in response to physiological stimuli, such as dehydration. Together, these observations point to important roles for brain-derived angiotensin peptides in a wide range of physiological functions.


title: Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus

text: BACKGROUND: In late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission. METHODOLOGY/PRINCIPALS: We developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available. CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation.


title: Influence of temporary migration on the transmission of infectious diseases in a migrants' home village

text: Abstract The number of temporary migrant workers from rural areas to urban areas in emerging market economies like China has increased dramatically since the early 1980s. Temporary migrant workers have been labeled as the major driving force for the rising incidence of infectious diseases in cities. However, it has not been well recognized that temporary migration indeed may have tremendous impacts on the spread of infectious diseases in migrants' home villages. In this paper, by proposing a delay differential equation model, we provide a framework to study the influence of temporary migration on the transmission of infectious diseases in a migrant workers' home village. The model is shown to admit a unique positive equilibrium which is locally asymptotically stable and is globally asymptotically stable under certain conditions. This implies that the disease always persists at a constant level. Considering tuberculosis as an example, we explore various disease prevention and control strategies numerically to demonstrate how migration related parameters affect the early outbreak of the disease. We find that a single control strategy, such as reducing the migration time period alone, has little effect on reducing the disease endemic level. For disease prevention and control, temporary migrant workers should be identified as the top target group, and a combination of several prevention strategies should be implemented.


title: Rinitis y rinosinusitis agudas del adulto

text: Las rinitis y rinosinusitis agudas son afecciones frecuentes y benignas en la mayoría de los casos. Su diagnóstico es esencialmente clínico. La dificultad de su tratamiento consiste en diferenciar las formas víricas, más frecuentes y banales, de las formas bacterianas, que son infrecuentes pero potencialmente graves. En este artículo se resumen las recomendaciones recientes, que se basan en la evidencia actual e insisten en los criterios diagnósticos clínicos, las indicaciones de las pruebas complementarias, la eficacia de los distintos tratamientos, así como la importancia de la información y de la educación de los pacientes. Los futuros trabajos en este ámbito deberán permitir seleccionar con más precisión a los pacientes que requieren realmente una antibioticoterapia y evitar de ese modo unos gastos sanitarios considerables, así como la aparición de cepas bacterianas resistentes.


title: Biomolecular NMR: a chaperone to drug discovery

text: Biomolecular NMR now contributes routinely to every step in the development of new chemical entities ahead of clinical trials. The versatility of NMR — from detection of ligand binding over a wide range of affinities and a wide range of drug targets with its wealth of molecular information, to metabolomic profiling, both ex vivo and in vivo — has paved the way for broadly distributed applications in academia and the pharmaceutical industry. Proteomics and initial target selection both benefit from NMR: screenings by NMR identify lead compounds capable of inhibiting protein–protein interactions, still one of the most difficult development tasks in drug discovery. NMR hardware improvements have given access to the microgram domain of phytochemistry, which should lead to the discovery of novel bioactive natural compounds. Steering medicinal chemists through the lead optimisation process by providing detailed information about protein–ligand interactions has led to impressive success in the development of novel drugs. The study of biofluid composition — metabonomics — provides information about pharmacokinetics and helps toxicological safety assessment in animal model systems. In vivo, magnetic resonance spectroscopy interrogates metabolite distributions in living cells and tissues with increasing precision, which significantly impacts the development of anticancer or neurological disorder therapeutics. An overview of different steps in recent drug discovery is presented to illuminate the links with the most recent advances in NMR methodology.


Freedom or money? The dilemma of migrant live‐in elderly carers in times of COVID‐19


title: Development of a smartphone-based rapid dual fluorescent diagnostic system for the simultaneous detection of influenza A and H5 subtype in avian influenza A-infected patients

text: Accurate and rapid diagnosis of highly pathogenic avian influenza A H5N1 is of critical importance for the effective clinical management of patients. Here, we developed a rapid and simultaneous detection toolkit for influenza A H5 subtype viruses in human samples based on a bioconjugate of quantum dots (QDs) assembly and a smartphone-based rapid dual fluorescent diagnostic system (SRDFDS). Methods: Two types of QDs were assembled on a latex bead to enhance the detection sensitivity and specificity of influenza A infection (QD580) and H5 subtype (QD650). The dual signals of influenza A and H5 subtype of H5N1-infected patients were detected simultaneously and quantified separately by SRDFDS equipped with two emission filters. Results: Our results showed a high sensitivity of 92.86% (13/14) and 78.57% (11/14), and a specificity of 100% (38/38, P < 0.0001) and 97.37% (37/38) for influenza A and H5 subtype detection, respectively. Conclusion: Therefore, our multiplex QD bioconjugates and SRDFDS-based influenza virus detection toolkit potentially provide accurate and meaningful diagnosis information with improved detection accuracies and sensitivities for H5N1 patients.


Understanding risks, mitigation and innovation for surgery in a COVID‐19 world


title: Therapeutic potential of coumarins as antiviral agents

text: Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure–activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.


title: Endotracheal Intubation Using a Direct Laryngoscope and the Protective Performances of Respirators: A Randomized Trial

text: Purpose. Emergency physicians are at risk for infection during invasive procedures, and the respirators can reduce this risk. This study aimed to determine whether endotracheal intubation using direct laryngoscopes affected protection performances of respirators. Methods. A randomized crossover study of 24 emergency physicians was performed. We performed quantitative fit tests using respirators (cup type, fold type without a valve, and fold type with a valve) before and during intubation. The primary outcome was respirators' fit factors (FF), and secondary outcomes were acceptable protection (percentage of scores above 100 FF [FF%]). Results. 24 pieces of data were analyzed. Compared to fold-type respirator without a valve, FF and FF% values were lower when participants wore a cup-type respirator (200 FF [200-200] versus 200 FF [102.75–200], 100% [78.61–100] versus 74.16% [36.1–98.9]; all P < 0.05) or fold-type respirator with a valve (200 FF [200-200] versus 142.5 FF [63.50–200], 100% [76.10–100] versus 62.50% [8.13–100]; all P < 0.05). There were no significant differences in intubation time and success rate according to respirator types. Conclusions. Motion during endotracheal intubation using direct laryngoscopes influenced the protective performance of some respirators. Therefore, emergency physicians should identify and wear respirators that provide the best personalized fit for intended tasks.


Reply to: “Biologics for psoriasis during COVID-19 outbreak”


title: Disinfection and Sterilization in Health Care Facilities An Overview and Current Issues

text: When properly used, disinfection and sterilization can ensure the safe use of invasive and noninvasive medical devices. The method of disinfection and sterilization depends on the intended use of the medical device: critical items (contact sterile tissue) must be sterilized before use; semicritical items (contact mucous membranes or nonintact skin) must be high-level disinfected; and noncritical items (contact intact skin) should receive low-level disinfection. Cleaning should always precede high-level disinfection and sterilization. Current disinfection and sterilization guidelines must be strictly followed.


title: The Role of the Military in Russian Politics and Foreign Policy Over the Past 20 Years

text: Abstract The Vladimir Putin regime has framed the Russian national idea in terms of security and militarization, both domestically and internationally. This unifying vision emerged as a reaction against the 1990s and blended together a cultivation of militant and anti-Western patriotism, Soviet nostalgia, and religious orthodoxy. Emphasis on cultivation of the youth has been another key defining feature of these efforts. This vision required a growing Russian presence regionally and globally, which in turn necessitated restoration of Russian military power. It resulted in growing self-confidence, internal repressions, and external military interventionism. There are glimmers of hope, but the Putin regime has shown that it will fight to stay in power, and the cult of militarization which has permeated multiple aspects of the Russian society will influence Russia's uncertain future.


title: Initial validation of the general attitudes towards Artificial Intelligence Scale

text: Abstract A new General Attitudes towards Artificial Intelligence Scale (GAAIS) was developed. The scale underwent initial statistical validation via Exploratory Factor Analysis, which identified positive and negative subscales. Both subscales captured emotions in line with their valence. In addition, the positive subscale reflected societal and personal utility, whereas the negative subscale reflected concerns. The scale showed good psychometric indices and convergent and discriminant validity against existing measures. To cross-validate general attitudes with attitudes towards specific instances of AI applications, summaries of tasks accomplished by specific applications of Artificial Intelligence were sourced from newspaper articles. These were rated for comfortableness and perceived capability. Comfortableness with specific applications was a strong predictor of general attitudes as measured by the GAAIS, but perceived capability was a weaker predictor. Participants viewed AI applications involving big data (e.g. astronomy, law, pharmacology) positively, but viewed applications for tasks involving human judgement, (e.g. medical treatment, psychological counselling) negatively. Applications with a strong ethical dimension led to stronger discomfort than their rated capabilities would predict. The survey data suggested that people held mixed views of AI. The initially validated two-factor GAAIS to measure General Attitudes towards Artificial Intelligence is included in the Appendix.


title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19)

text: Abstract The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.


title: MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017

text: We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.


title: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity

text: The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.


title: Galidesivir limits Rift Valley fever virus infection and disease in Syrian golden hamsters

text: Abstract Rift Valley fever virus (RVFV) is a mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula. There are no approved antiviral therapies or vaccines available to treat or prevent severe disease associated with RVFV infection in humans. The adenosine analog, galidesivir (BCX4430), is a broad-spectrum antiviral drug candidate with in vitro antiviral potency (EC50 of less than 50 μM) in more than 20 different viruses across eight different virus families. Here we report on the activity of galidesivir in the hamster model of peracute RVFV infection. Intramuscular and intraperitoneal treatments effectively limited systemic RVFV (strain ZH501) infection as demonstrated by significantly improved survival outcomes and the absence of infectious virus in the spleen and the majority of the serum, brain, and liver samples collected from infected animals. Our findings support the further development of galidesivir as an antiviral therapy for use in treating severe RVFV infection, and possibly other related phleboviral diseases.


title: Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

text: The recent pandemic of COVID‐19, caused by SARS‐CoV‐2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS‐CoV and MERS‐CoV. Human ACE2 is now established as a receptor for the SARS‐CoV‐2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross‐species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS‐CoV‐2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2‐spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS‐CoV‐2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild‐type molecule. Most ACE2 variants showed a similar binding affinity for SARS‐CoV‐2 spike protein as observed in the complex structure of wild‐type ACE2 and SARS‐CoV‐2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS‐CoV‐2 infection driven by ACE2 allelic variants.


Preparing for the Next Pandemic: Lessons Learned from Severe Respiratory Distress Syndrome


title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques

text: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.


title: Pre-B acute lymphoblastic leukemia expresses cell surface nucleolin as a 9-O-acetylated sialoglycoprotein

text: Precursor B acute lymphoblastic leukemias (pre-B ALLs) abnormally express a specific glycan structure, 9-O-acetylated sialic acid (9-O-Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, we establish that nucleolin (NCL), a protein implicated in cancer, contains 9-O-Ac-Sia. Surprisingly, antibodies against the glycolipid 9-O-Ac-Sia GD3 also detected 9-O-Ac-Sia NCL. NCL is present on the surface of pre-B ALL cells as a sialoglycoprotein that is partly 9-O-acetylated and conversely, 9-O-Ac-Sia-containing structures other than NCL are present on these cells as well. Interestingly, NCL and the 9-O-Ac-Sia signal had less co-localization on normal pre-B cells. We also investigated regulation of NCL on the cell surface and found that sialidase treatment increased the percentage of cells positive for cell surface NCL, suggesting that sialylation of NCL promotes internalization. Treatment of pre-B ALL cells with the chemotherapy drug vincristine also increased the percentage of cells with surface NCL and correlated with increased 9-O-Ac-Sia expression. All tested leukemia cells including primary samples expressed NCL, suggesting it as a possible therapeutic target. We confirmed this by showing inhibition of cell proliferation in some pre-B ALLs by exposure to a NCL-specific aptamer AS1411.


title: A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types

text: Abstract Genotyping of single nucleotide polymorphisms (SNPs) in point-of-care (POC) settings could be further improved through simplifying the treatment of samples. In this study, we devised an accurate, rapid and easy-to-use SNP detection system based on direct loop-mediated isothermal amplification (LAMP) without DNA extraction, known as Direct-LAMP. Samples from various sources (including whole blood, dried blood spot, buccal swab and saliva), treated with NaOH, can be used directly in amplification. The turnaround time was about 30 min from sample collection to provision of results. The accuracy was evaluated by assessing the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, which are better known for their critical role in folate and ethanol metabolism, respectively. Completely consistent genotyping results reveal that Direct-LAMP is generally concordant with sequencing. This system can serve as a very promising platform in the fields of disease predisposition, drug metabolism and personalized medicine.


title: Evidence of Recombinant Strains of Porcine Epidemic Diarrhea Virus, United States, 2013

text: To investigate the evolutionary process by which porcine epidemic diarrhea virus (PEDV) in the United States hypothetically descended from strains in China, we analyzed PEDV-positive samples collected in China during January 2012–July 2013. Recombination in 2 strain sublineages was likely associated with identification of PEDV in the United States in 2013.


title: Optimization of Codon Usage of Poxvirus Genes allows for Improved Transient Expression in Mammalian Cells

text: Transient expression of viral genes from certain poxviruses in uninfected mammalian cells can sometimes be unexpectedly inefficient. The reasons for poor expression levels can be due to a number of features of the gene cassette, such as cryptic splice sites, polymerase II termination sequences or motifs that lead to mRNA instability. Here we suggest that in some cases the problem of low protein expression in transfected mammalian cells may be due to inefficient codon usage. We have observed that for many poxvirus genes from the yatapoxvirus genus this deficiency can be overcome by synthesis of the gene with codon sequences optimized for expression in primate cells. This led us to examine colon usage across 2-dozen sequenced members of the Poxviridae. We conclude that codon usage is surprisingly divergent across the different Poxviridae genera but is much more conserved within a single genus. Thus, Poxviridae genera can be divided into distinct groups based on their observed codon bias. When viewed in this context, successful transient expression of transfected poxvirus genes in uninfected mammalian cells can be more accurately predicted based on codon bias. As a corollary, for specific poxvirus genes with less favorable codon usage, codon optimization can result in profoundly increased transient expression levels following transfection of uninfected mammalian cell lines.


title: The antimalarial ferroquine: from bench to clinic

text: Ferroquine (FQ, SSR97193) is currently the most advanced organometallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocenecontaining compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.


title: The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China

text: The novel coronavirus can be transmitted from person to person with infection ranging from mild disease to severe pneumonia and radiological abnormalities on chest CT for most patients improved after RT-PCR conversion.


title: Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis

text: SUMMARY: This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. INTRODUCTION: The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. METHODS: We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. RESULTS: Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30–1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09–1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p (non-linear) < 0.001 and p (non-linear) = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI −0.03 to 0.06, p = 0.582). CONCLUSIONS: SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-016-3824-z) contains supplementary material, which is available to authorized users.


title: A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats

text: The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.


title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells

text: CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy.


title: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study

text: BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19–positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.


title: Optimization of the Production Process and Characterization of the Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1), a SARS Vaccine Candidate

text: From 2002 to 2003, a global pandemic of severe acute respiratory syndrome (SARS) spread to 5 continents and caused 8000 respiratory infections and 800 deaths. To ameliorate the effects of future outbreaks as well as to prepare for biodefense, a process for the production of a recombinant protein vaccine candidate is under development. Previously, we reported the 5 L scale expression and purification of a promising recombinant SARS vaccine candidate, RBD219-N1, the 218–amino acid residue receptor-binding domain (RBD) of SARS coronavirus expressed in yeast–Pichia pastoris X-33. When adjuvanted with aluminum hydroxide, this protein elicited high neutralizing antibody titers and high RBD-specific antibody titers. However, the yield of RBD219-N1 (60 mg RBD219-N1 per liter of fermentation supernatant; 60 mg/L FS) still required improvement to reach our target of >100 mg/L FS. In this study, we optimized the 10 L scale production process and increased the fermentation yield 6- to 7-fold to 400 mg/ L FS with purification recovery >50%. A panel of characterization tests indicated that the process is reproducible and that the purified, tag-free RBD219-N1 protein has high purity and a well-defined structure and is therefore a suitable candidate for production under current Good Manufacturing Practice and future phase-1 clinical trials.


title: Respiratory viral diseases: access to RNA interference therapy

text: This review summarizes recent experimental achievements in the area of the development of new RNA interference (RNAi) therapeutics for the treatment of viral respiratory diseases. Delivery of siRNA to their intended target tissue remains the biggest problem for most therapeutic applications of these compounds. Appropriate formulations and chemical modifications for improved stability will boost the probability of utilization of RNAi drugs in the clinical applications.


title: Insight into COVID‐2019 for pediatricians

text: Since December 2019, patients with unexplained pneumonia have been found in Wuhan City, Hubei Province, China. The pathogen in these cases is a new type of coronavirus. The World Health Organization confirmed this diagnosis and named the pathogen SARSCoV‐2. The disease caused by SARSCoV‐2 is called Corona Virus Disease (COVID‐2019). The virus is highly infectious and pathogenic, causing human‐to‐human transmission. At present, SARSCoV‐2 is still rampant in the world. Zhengzhou City in Henan Province serves as an example, 102 people have been confirmed to be infected with SARSCoV‐2 (at 24:00 on February 5th, 2020), including three children, the youngest is 4 years old. From the perspective of clinical pediatricians as the first line fighting the epidemic, this paper will discuss the clinical characteristics, prevention and control measures, outcomes, diagnosis, and treatment of pediatric cases.


title: Fever in the returning traveller

text: Abstract Fever is a common reason for acute hospital admission for tropical illness in UK referral units. A sensible working diagnosis can usually be formulated from a careful history and examination and initial simple investigations. The history should include details of exactly where the patient has been, what conditions he or she was living in, and the exact dates of arrival and departure. The quality of pre-travel advice and vaccinations, adherence to chemoprophylaxis against malaria, avoidance of insect bites and general behaviour abroad (including sexual history) are also important. Localizing features of the illness should be sought on examination. Maintain a high index of suspicion for underlying HIV. The most important illness to consider and exclude is malaria (about 40% of cases), and most of the remainder have cosmopolitan viral infections or imported infections such as an arbovirus (dengue), enteric fever or viral hepatitis. Rarer causes are usually evident from the history and examination, which presupposes a good knowledge of geographical medicine. Initial investigations should include adequate malaria films (supplemented by quick antigen detection tests in many laboratories) and blood count, repeated as necessary, blood, urine and faecal cultures, serum biochemistry, chest radiography and other imaging (e.g. liver ultrasonography) as indicated. In patients in whom malaria is suspected despite negative films, the combination of thrombocytopenia and splenomegaly is supportive but not diagnostic of malaria.


title: Comparison of the Amino Acid Sequence and Phylogenetic Analysis of the Peplomer, Integral Membrane and Nucleocapsid Proteins of Feline, Canine and Porcine Coronaviruses

text: Complete nucleotide sequences were determined by cDNA cloning of peplomer (S), integral membrane (M) and nucleocapsid (N) genes of feline infectious peritonitis virus (FIPV) type I strain KU‐2, UCD1 and Black, and feline enteric coronavirus (FECV) type II strain 79–1683. Only M and N genes were analyzed in strain KU‐2 and strain 79–1683, which still had unknown nucleotide sequences. Deduced amino acid sequences of S, M and N proteins were compared in a total of 7 strains of coronaviruses, which included FIPV type II strain 79–1146, canine coronavirus (CCV) strain Insavc‐1 and transmissible gastroenteritis virus of swine (TGEV) strain Purdue. Comparison of deduced amino acid sequences of M and N proteins revealed that both M and N proteins had an identity of at least 90% between FIPV type I and type II. The phylogenetic tree of the M and N protein‐deduced amino acid sequences showed that FIPV type I and type II form a group with FECV type II, and that these viruses were evolutionarily distant from CCV and TGEV. On the other hand, when the S protein‐deduced amino acid sequences was compared, identity of only about 45% was found between FIPV type I and type II. The phylogenetic tree of the S protein‐deduced amino acid sequences indicated that three strains of FIPV type I form a group, and that it is a very long distance from the FIPV type II, FECV type II, CCV and TGEV groups.


title: COVID‐19: Risk groups, mechanistic insights and challenges

text: As Dr. Thomson eloquently notes in his valuable letter [1], underlying respiratory diseases appear to be less of a risk factor for poor outcome in COVID-19 patients than either underlying cardiovascular disease or diabetes. This intriguing finding emerged from several studies that examined underlying medical conditions in COVID-19 patients.


title: Chapter Three Nucleic Acid Induced Interferon and Inflammasome Responses in Regulating Host Defense to Gastrointestinal Viruses

text: Abstract The gut bacterial and fungal communities residing in the gastrointestinal tract have undisputed far-reaching effects in regulating host health. In the meantime, however, metagenomic sequencing efforts are revealing enteric viruses as the most abundant dimension of the intestinal gut ecosystem, and the first gut virome-wide association studies showed that inflammatory bowel disease as well as type 1 diabetes could be linked to the presence or absence of particular viral inhabitants in the intestine. In line with the genetic component of these human diseases, mouse model studies demonstrated how beneficial functions of a resident virus can switch to detrimental inflammatory effects in a genetically predisposed host. Such viral-induced intestinal immune disturbances are also recapitulated by several gastrointestinal infectious viruses such as rotavirus and human norovirus. This wide range of viral effects on intestinal immunity emphasizes the need for understanding the innate immune responses to gastrointestinal viruses. Numerous nucleic acid sensors such as DexD/H helicases and AIM2 serve as cytosolic viral guardians to induce antiviral interferon and/or pro-inflammatory inflammasome responses. In both cases, pioneering examples are emerging in which RNA helicases cooperate with particular Nod-like receptors to trigger these cellular responses to enteric viruses. Here we summarize the reported beneficial versus detrimental effects of enteric viruses in the intestinal immune system, and we zoom in on the mechanisms through which sensing of nucleic acids from these enteric viruses trigger interferon and inflammasome responses.


title: Psychiatric symptoms and psychosocial functioning among hospital personnel during the Gaza War: A repeated cross–sectional study

text: Abstract Studies of mental health among hospital personnel during armed conflict are scarce and usually include single time point investigations without a comparison group. The authors compared the psychiatric symptoms and psychosocial functioning of exposed and unexposed hospital personnel at two time points. The research was conducted during 2009 and included a survey of two random samples of hospital personnel (physicians and nurses), one collected during the Gaza War and the other 6months later. Each sample included hospital personnel who were exposed to war-related stress and others who were not (Study 1: n =67 and 74 for exposed and unexposed, respectively; Study 2: n =57 and 50 for exposed and unexposed, respectively). Levels of psychiatric symptoms and psychosocial functioning were measured. Compared to unexposed hospital personnel, exposed hospital personnel had a significantly higher level of post–traumatic symptoms during the Gaza War and 6months later. In addition, during the Gaza War, exposed hospital personnel had a significantly higher level of depressive symptoms. However, in the second study, depressive symptoms were similar to those found in the unexposed group. These findings may suggest that war-related stress is associated with post–traumatic symptoms among hospital personnel even 6months after exposure.


title: Determinants of emergency response responsibility perceptions in the local public health workforce after China’s health sector restructuring

text: BACKGROUND: Local health departments are the backbone of public health emergency (PHE) response plans. The front line of emergency response preparedness is people. Role perceptions of individual staff members of a given organization strongly affect response probability and performance. Therefore, the aim of this study was to determine local public health employees’ perceptions of emergency response responsibilities, identify factors that influence their perception, and indicate the challenges and bottlenecks of PHE response in the Health Inspection Institution (HII) after its separation from China’s multiple Centers for Disease Control and Prevention (CDC). METHODS: We used a stratified randomized sample survey to examine HII workers’ knowledge of their own duties concerning PHE response in 17 facilities in Heilongjiang, a province in northeastern China. Data were collected from May to July 2010 using a 9-item combined question inquiring about the workers’ statutory duties. RESULTS: Of 348 administered surveys, 309 were returned for an overall response rate of 88.8 %. Overall, the correct recognition rate of PHE responsibilities was low. Some HII workers were confused about their responsibilities required by law, regulations, and emergency response plans. A quarter of all the respondents had the lowest knowledge for PHE responsibilities. Factors influencing their perceptions of responsibilities were department, work experience in a CDC, and PHE response experience. CONCLUSIONS: To improve preparedness for a PHE, efforts are needed to train, support, and monitor the workers’ knowledge and competencies in PHEs as part of an organizational change; the worker’s knowledge of their responsibilities should be measured and used as an indicator of preparedness for a PHE, and training should be undertaken where there are deficiencies. Management should also encourage workers in the departments of food hygiene/school health surveillance to be more involved in PHE preparedness and response issues.


Hypocortisolism in survivors of SARS


title: Adenovirus-based vaccines against avian-origin H5N1 influenza viruses

text: Abstract Since 1997, human infection with avian H5N1, having about 60% mortality, has posed a threat to public health. In this review, we describe the epidemiology of H5N1 transmission, advantages and disadvantages of different influenza vaccine types, and characteristics of adenovirus, finally summarizing advances in adenovirus-based H5N1 systemic and mucosal vaccines.