title: Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus

text: Abstract We investigated comparatively the interactions of host cells with two types of rabies virus G protein, an avirulent type G (Gln) and a virulent type G (Arg) protein, having glutamine and arginine at position 333, respectively. For this purpose, we established four types of cell lines (referred to as G(Gln)-NA, G(Arg)-NA, G(Gln)-BHK, and G(Arg)-BHK cells, respectively) by transfecting either the G(Gln)-cDNA or G(Arg)-cDNA into two kinds of cells, murine neuroblastoma C1300 (clone NA) and nonneuronal BHK-21. Both G(Gln)-NA and G(Arg)-NA cells produced G proteins when they were treated with 5 mM sodium butyrate, but only G(Arg)-NA cells formed syncytia at the neutral pH, which was suppressed by anti-G antiserum. The sodium butyrate-treated G(Arg)-NA cells fused also with sodium butyrate-treated NA cells under coculture conditions, but neither with untreated NA cells nor with BHK-21 cells. On the other hand, both G(Gln)-BHK and G(Arg)-BHK cells constitutively produced G proteins, but no syncytium was produced at the neutral pH. G(Arg)-BHK cells, however, formed syncytia with the sodium butyrate-treated NA cells when they were cocultured. These results suggest that only G(Arg) has a potential ability to produce syncytia of NA cells regardless of cell types by which G(Arg) protein was produced and also suggest that a certain cellular factor(s) is required for the syncytium formation, the factor(s) which is lacking in BHK-21 and untreated NA cells but is produced by the sodium butyrate-treated NA cells.


title: The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century

text: At the beginning of the 21st century, a new deadly infectious disease known as severe acute respiratory syndrome (SARS) was recognized as a global public health threat. Subsequently, ten years after the initial SARS cases occurred in 2002, new cases of another atypical respiratory disease caused worldwide concern. This disease became known as Middle East respiratory syndrome (MERS) and was even more lethal than SARS. Currently, history has repeated itself with the emergence of a new Chinese epidemic at the end of 2019. For this respiratory disease, called COVID-19, a novel coronavirus (SARS-CoV-2) was identified as the etiologic agent. In sum, SARS, MERS and COVID-19 are caused by recently discovered coronaviruses that cause flu-like illnesses, but with a clinical outcome that tends to be more severe. As a result of the current importance of coronaviruses in global public health, we conducted a review to summarize and update, above all, the epidemiological historical aspects of the three major diseases in humans caused by coronaviral infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04628-0) contains supplementary material, which is available to authorized users.


title: Adult cardiac critical care at the King Abdulaziz Cardiac Center

text: Adult Cardiac Critical Cardiac Care division at the King Abdulaziz Cardiac Center – Riyadh, Saudi Arabia, was created in 2011 to address the critical care needs of cardiac surgery and adult cardiology patients that were beyond the scope of their specialties. The division offers its services in two semi-closed intensive care units consisting of 17 beds of Level 3 care. The concept and rationale behind this relatively new subspecialty and its organization in our center are presented in this brief report.


title: Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection

text: HIV infection of CD4(+) T cells induces a range of host transcriptional changes in mRNAs as well as microRNAs that may coordinate changes in mRNAs. To survey these dynamic changes, we applied next-generation sequencing, analyzing the small RNA fraction of HIV-infected cells at 5, 12, and 24 h postinfection (RNA-Seq). These time points afforded a view of the transcriptomic changes occurring both before and during viral replication. In the resulting small RNA-Seq data set, we detected a phased pattern of microRNA expression. Largely distinct sets of microRNAs were found to be suppressed at 5 and 12 h postinfection, and both sets of changes rebounded later in infection. A larger set of microRNA changes was observed at 24 h postinfection. When integrated with mRNA expression data, the small RNA-Seq data indicated a role for microRNAs in transcriptional regulation, T cell activation, and cell cycle during HIV infection. As a unique benefit of next-generation sequencing, we also detected candidate novel host microRNAs differentially expressed during infection, including one whose downregulation at 24 h postinfection may allow full replication of HIV to proceed. Collectively, our data provide a uniquely comprehensive view of the changes in host microRNAs induced by HIV during cellular infection.


title: Infectious aetiologies in elderly patients hospitalised with non‐pneumonic lower respiratory tract infection

text: Objective: to identify the infectious aetiologies of non‐pneumonic lower respiratory tract infections in hospitalised elderly patients, and to characterise the patients in terms of demographic, clinical and therapeutic variables. Design: a prospective, non‐interventional, purely serologically based diagnostic study. Setting: a tertiary university hospital in southern Israel. Subjects: 133 elderly patients hospitalised for non‐pneumonic lower respiratory tract infections. Methods: paired sera were obtained for each of the hospitalisations and were tested using immunofluorescence or enzyme immunoassay methods to identify 13 different pathogens. Only significant changes in antibody titers or levels between the paired sera were considered diagnostic. Results: at least one infectious aetiology was identified in 77 patients (58%). At least one of seven viral aetiologies was identified in 52 patients (39%). A bacterial aetiology was identified in 27 patients (20%) including Streptococcus pneumoniae in 24 (18%). An atypical bacterium was found in 27 patients (20%) including Mycoplasma pneumoniae in 15 (11%) and Legionella spp. in nine (7%). More than one aetiology was found in 23 patients (17%). One hundred and twenty nine patients (96%) suffered from serious chronic co‐morbidity. One hundred and twenty one patients received antibiotics during their hospitalisation, 106 (80%) with a beta‐lactam and 42 (31%) with another antibiotic. Conclusions: non‐pneumonic lower respiratory tract infection is caused in hospitalised elderly patients by a broad spectrum of aetiological agents, primarily respiratory viruses with a significant, though lesser, prevalence of classical and atypical bacteria. Despite this distribution of aetiologies, most patients are treated with beta‐lactam antibiotics. The indication for antibiotic therapy in these patients and the choice of antibiotic preparation should be addressed in further studies.


Increased rate of ruptured ectopic pregnancy in the COVID‐19 pandemic: an analysis from the North of Italy


title: Population-based surveys and interventions for mental health literacy in China during 1997–2018: a scoping review

text: BACKGROUND: This scoping review maps population-based surveys and mental health literacy (MHL) interventions undertaken in China during 1997–2018 in order to identify research gaps. METHOD: Following Arksey and O’Malley’s framework for a scoping review, five English databases (Medline, PsycINFO, Cochrane library, Web of Science and CINAHL) and two Chinese ones (CNKI and WanFang) were systematically searched, identifying both reports of surveys and evaluation of interventions from Jan 1997 to Oct 2018. RESULTS: MHL research has developed rapidly in China in terms of numbers of studies and geographic coverage over the past two decades. There were 350 peer-reviewed publications included in this review, covering diverse settings and participants. Of these publications, 313 (89.4%) were published in Chinese-language journals and 37 in English-language journals; 303 (86.6%) reported on survey findings and 47 reported on the evaluation of MHL interventions. MHL research in China has mainly focused on the assessment of mental health-related knowledge and beliefs. Much less attention has been given to developing and evaluating relevant interventions. MHL related to general mental health and suicide were most commonly studied, with less focus on specific disorders, although some studies covered depression, psychosis and anxiety disorders. The majority of MHL tools utilized in the studies reported in this review were developed in China (n = 97, 80.2% ) and almost half of these studies (57.8%) did not provide enough details concerning psychometrics. CONCLUSIONS: More interventions targeting the general public and aiming to improve MHL and promote behaviour change, are needed in China. These should be evaluated with high-quality study designs, such as randomised controlled trials. Proper validation of tools used for measuring MHL should also be addressed in future studies.


title: Virus Removal by Disinfection of Effluents

text: KEYWORDS Enteric-viruses, effluent, disinfection, halogens, chlorine dioxide, ozone, peracetic acid


title: PCR diagnostics: In silico validation by an automated tool using freely available software programs

text: Abstract PCR diagnostics are often the first line of laboratory diagnostics and are regularly designed to either differentiate between or detect all pathogen variants of a family, genus or species. The ideal PCR test detects all variants of the target pathogen, including newly discovered and emerging variants, while closely related pathogens and their variants should not be detected. This is challenging as pathogens show a high degree of genetic variation due to genetic drift, adaptation and evolution. Therefore, frequent re-evaluation of PCR diagnostics is needed to monitor its usefulness. Validation of PCR diagnostics recognizes three stages, in silico, in vitro and in vivo validation. In vitro and in vivo testing are usually costly, labour intensive and imply a risk of handling dangerous pathogens. In silico validation reduces this burden. In silico validation checks primers and probes by comparing their sequences with available nucleotide sequences. In recent years the amount of available sequences has dramatically increased by high throughput and deep sequencing projects. This makes in silico validation more informative, but also more computing intensive. To facilitate validation of PCR tests, a software tool named PCRv was developed. PCRv consists of a user friendly graphical user interface and coordinates the use of the software programs ClustalW and SSEARCH in order to perform in silico validation of PCR tests of different formats. Use of internal control sequences makes the analysis compliant to laboratory quality control systems. Finally, PCRv generates a validation report that includes an overview as well as a list of detailed results. In-house developed, published and OIE-recommended PCR tests were easily (re-) evaluated by use of PCRv. To demonstrate the power of PCRv, in silico validation of several PCR tests are shown and discussed.


Is it too premature to recommend against laparoscopic emergency surgery in COVID‐19 patients?


title: Influenza not MERS CoV among returning Hajj and Umrah pilgrims with respiratory illness, Kashmir, north India, 2014–15

text: Abstract Background The increasing reports of Middle East Respiratory Syndrome (MERS) caused by MERS coronavirus (MERS-CoV) from many countries emphasize its importance for international travel. Muslim pilgrimages of Hajj and Umrah involve mass gatherings of international travellers. We set out to assess the presence of influenza and MERS-CoV in Hajj/Umrah returnees with acute respiratory infection. . Methods Disembarking passengers (n = 8753) from Saudi Arabia (October 2014 to April 2015) were interviewed for the presence of respiratory symptoms; 977 (11%) reported symptoms and 300 (age 26–90, median 60 years; 140 male) consented to participate in the study. After recording clinical and demographic data, twin swabs (nasopharyngeal and throat) were collected from each participant, pooled in viral transport media and tested by real-time RT PCR for MERS-CoV and influenza A and B viruses and their subtypes. Results The participants had symptoms of 1–15 days (median 5d); cough (90%) and nasal discharge (86%) being the commonest. None of the 300 participants tested positive for MERS-CoV; however, 33 (11%) tested positive for influenza viruses (A/H3N2 = 13, A/H1N1pdm09 = 9 and B/Yamagata = 11). Eighteen patients received oseltamivir. No hospitalizations were needed and all had uneventful recovery. Conclusion Despite a high prevalence of acute respiratory symptoms, MERS coV was not seen in returning pilgrims from Hajj and Umrah. However detection of flu emphasises preventive strategies like vaccination.


title: Insomnia during the COVID-19 pandemic in a Greek population

text: Insomnia is a major health issue associated with great psychological burden. Research of insomnia during a pandemic crisis is limited. The aim of the present study was to explore sleep difficulties during the COVID-19 pandemic in a Greek population. The three-day online survey included questions about sociodemographic characteristics, contact with COVID-19 and COVID-19-related negative attitudes, as well as the Athens Insomnia Scale (AIS), the Intolerance to Uncertainty scale (IUS), the De Jong Gierveld Loneliness scale (JGLS) and the Patient Health Questionnaire-2 (PHQ-2) Depression Scale. Altogether, 2,427 individuals participated in the study (2,363 of them provided all basic demographic data). Sleep problems were detected in 37.6% of the participants. Women and people in urban areas were more vulnerable to sleep problems, while younger age showed a non-significant trend. Those uncertain about having themselves, or someone close to them contacted the virus, also demonstrated elevated insomnia scores. Lastly, according to the regression analysis, higher levels of intolerance to uncertainty, COVID-19-related worry, loneliness, as well as more severe depressive symptoms, were all predictive of insomnia. Results may be used for the development of therapeutic strategies and implementation of social policies to support people with sleep difficulties.


title: Detection and clinical characteristics analysis of respiratory viruses in hospitalized children with acute respiratory tract infections by a GeXP‐based multiplex‐PCR assay

text: BACKGROUND: The information regarding viral epidemiology and clinical characteristics in hospitalized children with acute respiratory tract infection (ARTI) in central Fujian is limited. In this study, we aimed at analyzing the viral epidemiology and clinical characteristics of ARTI in hospitalized children admitted to The First Affiliated Hospital of Fujian Medical University. METHODS: Cohort of 386 hospitalized children (31 days to 15 years) diagnosed with ARTI admitted to the Department of Pediatrics from January 1, 2018, to December 31, 2018, was enrolled in this study. Nasopharyngeal swab or sputum samples on the day of hospitalization were tested for 11 viruses via a GeXP‐based multiplex‐PCR assay. The viral profiles and clinical characteristics were analyzed. RESULTS: The overall positive rate of the samples was 43.26% (167/386). Among the 167 positive samples, 134 (80.24%, 134/167) had a single virus and 33 (19.76%, 33/167) had multiple viruses. There was a significant difference in the frequency of single vs mixed infections among positive samples (80.24% vs 19.76%; χ (2) = 122.168, P = .000) as well as among the total examined samples (34.72% vs 8.55%; χ (2) = 77.945, P = .000). Human rhinovirus was the most prevalent virus (17.36%, 67/386), followed by influenza A (5.96%, 23/386) and human adenovirus (5.70%, 22/386). There was no significant difference in the etiological distribution of viral pathogens between males and females (χ (2) = 0.480, P = .489). Viral infections were more likely to occur in the winter‐spring months than in the summer‐autumn months (52.51% vs 33.53%, χ (2) = 13.830, P = .000). CONCLUSIONS: The GeXP‐based multiplex PCR is an accurate and high‐throughput assay allows us to quickly detect multiple respiratory viruses simultaneously in pediatric patients. Our study provides information on the viral profiles and clinical characteristics in hospitalized children with ARTI, which would help better effective prevention strategies.


title: From SARS to Avian Influenza: The Role of International Factors in China's Approach to Infectious Disease Control

text: Abstract Background Over the past decades global environmental change, globalization, urbanization, and the rise in movement of people have increased the risk for pandemic disease outbreaks. As environmental exposures do not respect state borders, a globalist concept of global health response has developed, which requires transparency and cooperation for coordinated responses to disease outbreaks. Countries that avoid cooperation on health issues for social or political reasons can endanger the global community. Objectives The aim of this study was to examine the rapid change in China's infectious disease policy between 2000 and 2013, from actively rejecting the assistance of international health experts during the HIV/AIDS and severe acute respiratory syndrome crises to following best-practice disease response policies and cooperating with international health actors during the 2013 avian influenza outbreak. Methods Using international relations theory, I examined whether international political factors had a major influence on this change. Using the case studies of international reputation, socialization with international organizations, and the securitization of infectious disease, this study examined the influence of international and domestic pressures on Chinese infectious disease policy. Findings Although international relations theory, especially theories popular in global health diplomacy literature, provide valuable insight into the role of international factors and foreign policy interests in China's changing approach to infectious disease control, it cannot provide viable explanations without considering the domestic interests of the Chinese government. Conclusion Analysis of state responses to infectious disease using international relations theories must consider domestic political factors.


title: Infectious Diseases of Dogs and Cats on Isabela Island, Galapagos

text: Background: Vaccination and importation of dogs and cats are prohibited in the Galapagos, resulting in a uniquely isolated population. The purpose of this study was to determine the prevalence of infectious diseases of dogs and cats that impact their health, could spill over to native wildlife, or sentinel diseases of concern to humans. Hypothesis: The isolation of dogs and cats in the Galapagos protects them from diseases common in mainland populations. Animals: Ninety‐five dogs and 52 cats presented during a neutering campaign. Methods: A prospective cross‐sectional study was performed. Blood was collected for serological and DNA evaluation of a panel of infectious diseases. Results: Antibodies against parvovirus (100%), parainfluenza virus (100%), adenovirus 1/2 (66–67%), and distemper virus (22%) were present in dogs. Dirofilaria immitis was also common in dogs (34%), with lower prevalences of Wolbachia pipiens (22%), Bartonella sp. (13%), Ehrlichia/Anaplasma spp. (1%), and Mycoplasma haemocanis (1%) observed. Antibodies against panleukopenia virus (67%), Toxoplasma gondii (63%), calicivirus (44%), and herpesvirus 1 (10%) were detected in cats. Feline leukemia virus antigen, feline immunodeficiency virus antibody, or coronavirus antibodies were not detected. Bartonella sp. (44%) infections were common in cats, but only one was infected with M. haemofelis. Conclusions and Clinical Importance: Despite their relative seclusion from the rest of the world, cats and dogs of Isabela were exposed to many pathogens found in mainland South America. Parasite prophylaxis, neutering, and strict enforcement of animal movement restrictions would control a majority of the diseases. In the absence of vaccination, a reservoir of susceptible animals remains vulnerable to new disease introductions.


title: Effectiveness of Noninvasive Positive Pressure Ventilation in the Treatment of Acute Respiratory Failure in Severe Acute Respiratory Syndrome

text: Objectives: To study the effectiveness of noninvasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory failure (ARF) in severe acute respiratory syndrome (SARS), and the associated infection risk. Methods: All patients with the diagnosis of probable SARS admitted to a regional hospital in Hong Kong from March 9 to April 28, 2003, and who had SARS-related respiratory distress complications were recruited for NIPPV usage. The health status of all health-care workers working in the NIPPV wards was closely monitored, and consent was obtained to check serum for coronavirus serology. Patient outcomes and the risk of SARS transmission to health-care workers were assessed. Results: NIPPV was applied to 20 patients (11 male patients) with ARF secondary to SARS. Mean age was 51.4 years, and mean acute physiology and chronic health evaluation II score was 5.35. Coronavirus serology was positive in 95% (19 of 20 patients). NIPPV was started 9.6 days (mean) from symptom onset, and mean duration of NIPPV usage was 84.3 h. Endotracheal intubation was avoided in 14 patients (70%), in whom the length of ICU stay was shorter (3.1 days vs 21.3 days, p < 0.001) and the chest radiography score within 24 h of NIPPV was lower (15.1 vs 22.5, p = 0.005) compared to intubated patients. Intubation avoidance was predicted by a marked reduction in respiratory rate (9.2 breaths/min) and supplemental oxygen requirement (3.1 L/min) within 24 h of NIPPV. Complications were few and reversible. There were no infections among the 105 health-care workers caring for the patients receiving NIPPV. Conclusions: NIPPV was effective in the treatment of ARF in the patients with SARS studied, and its use was safe for health-care workers.


title: Zoonotic Viral Diseases of Equines and Their Impact on Human and Animal Health

text: INTRODUCTION: Zoonotic diseases are the infectious diseases that can be transmitted to human beings and vice versa from animals either directly or indirectly. These diseases can be caused by a range of organisms including bacteria, parasites, viruses and fungi. Viral diseases are highly infectious and capable of causing pandemics as evidenced by outbreaks of diseases like Ebola, Middle East Respiratory Syndrome, West Nile, SARS-Corona, Nipah, Hendra, Avian influenza and Swine influenza. EXPALANTION: Many viruses affecting equines are also important human pathogens. Diseases like Eastern equine encephalitis (EEE), Western equine encephalitis (WEE), and Venezuelan-equine encephalitis (VEE) are highly infectious and can be disseminated as aerosols. A large number of horses and human cases of VEE with fatal encephalitis have continuously occurred in Venezuela and Colombia. Vesicular stomatitis (VS) is prevalent in horses in North America and has zoonotic potential causing encephalitis in children. Hendra virus (HeV) causes respiratory and neurological disease and death in man and horses. Since its first outbreak in 1994, 53 disease incidents have been reported in Australia. West Nile fever has spread to many newer territories across continents during recent years. It has been described in Africa, Europe, South Asia, Oceania and North America. Japanese encephalitis has expanded horizons from Asia to western Pacific region including the eastern Indonesian archipelago, Papua New Guinea and Australia. Rabies is rare in horses but still a public health concern being a fatal disease. Equine influenza is historically not known to affect humans but many scientists have mixed opinions. Equine viral diseases of zoonotic importance and their impact on animal and human health have been elaborated in this article. CONCLUSION: Equine viral diseases though restricted to certain geographical areas have huge impact on equine and human health. Diseases like West Nile fever, Hendra, VS, VEE, EEE, JE, Rabies have the potential for spread and ability to cause disease in human. Equine influenza is historically not known to affect humans but some experimental and observational evidence show that H3N8 influenza virus has infected man. Despite our pursuit of understanding the complexity of the vector-host-pathogen mediating disease transmission, it is not possible to make generalized predictions concerning the degree of impact of disease emergence. A targeted, multidisciplinary effort is required to understand the risk factors for zoonosis and apply the interventions necessary to control it.


title: A Poisson model of sequence comparison and its application to coronavirus phylogeny

text: Abstract In this paper, we propose two metrics to compare DNA and protein sequences based on a Poisson model of word occurrences. Instead of comparing the frequencies of all fixed-length words in two sequences, we consider (1) the probability of ‘generating’ one sequence under the Poisson model estimated from the other; (2) their different expression levels of words. Phylogenetic trees of 25 viruses including SARS-CoVs are constructed to illustrate our approach.


Thromboembolic Events in Patients with SARS-CoV-2


View from Portsmouth during COVID‐19 pandemic ward work


title: Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability

text: Abstract Background Dihydromyricetin (DMY) is an important plant flavonoid, which has received great attention due to its health-benefiting activities, including antioxidant, antimicrobial, anti-inflammatory, anticancer, antidiabetic and neuroprotective activities. DMY capsules have been sold in US as a nutraceutical supplement to prevent alcoholic hangovers. The major disadvantage associated with DMY is its chemical instability and poor bioavailability caused by the combined effects of its low solubility and poor membrane permeability. This limits its practical use in the food and pharmaceutical fields. Scope and approach The present paper gives an overview of the current methods for the identification and quantification of DMY. Furthermore, recent findings regarding the main biological properties and chemical stability of DMY, the metabolism of DMY as well as different approaches to increase DMY bioavailability in both aqueous and lipid phases are discussed. Key findings and conclusions Current trends on identification and quantification of DMY have been focused on spectral and chromatographic techniques. Many factors such as heat, pH, metal ions, could affect the chemical stability of DMY. Despite the diverse biological effects of DMY, DMY faces with the problem of poor bioavailability. Utilization of different delivery systems including solid dispersion, nanocapsule, microemuslion, cyclodextrin inclusion complexes, co-crystallization, phospholipid complexes, and chemical or enzymatic acylation has the potential to improve both the solubility and bioavailability. DMY digested in laboratory animals undergoes reduction, dehydroxylation, methylation, glucuronidation, and sulfation. Novel DMY delivery systems and basic pharmacokinetic studies of encapsulated DMY on higher animals and humans might be required in the future.


title: Recurrence or Relapse of COVID‐19 in Older Patients: A Description of Three Cases.

text: BACKGROUND: The coronavirus disease 2019 (COVID‐19) has infected millions of people worldwide, particularly in older adults. The first cases of possible re‐infection by SARS‐CoV‐2 were reported in April 2020 among older adults. DESIGN/SETTING: In this brief report, we present three geriatric cases with two episodes of SARS‐CoV‐2 infection separated by a symptom‐free interval.


title: Experimental coronavirus retinopathy (ECOR): Retinal degeneration susceptible mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early after virus infection

text: Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown. Herein, we show that IFN-α, IFN-β and IFN-γ act in concert as part of the innate immune response to the retinal infection. At day 2, high serum levels of IFN-γ, CXCL9 and CXCL10, were detected in BALB/c mice. Moreover, elevated levels of CXCL9 and CXCL10 gene expression were detected in retinal tissue. Although IFN-γ and the chemokines were detected in CD-1 mice, they were at significantly lower levels compared to BALB/c mice. These augmented innate responses observed correlated with the development of autoimmune reactivity and retinal degeneration and thus may contribute to the pathogenic processes.


title: Mental health status of the general population, healthcare professionals, and university students during 2019 coronavirus disease outbreak in Jordan: A cross‐sectional study

text: BACKGROUND: The emergence of COVID‐19 global pandemic coupled with high transmission rate and mortality has created an unprecedented state of emergency worldwide. This global situation may have a negative impact on the psychological well‐being of individuals which in turn impacts individuals' performance. This study aims to explore the prevalence of depression and anxiety among the GP, HCPs, and USs during COVID‐19 outbreak, and to identify key population(s) who might need psychological intervention. METHODS: A cross‐sectional study using an online survey was conducted in Jordan between 22 and 28 March 2020 to explore the mental health status (depression and anxiety) of the general population, healthcare professionals, and university students during the COVID‐19 outbreak. The Patient Health Questionnaire (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) were used to assess depression and anxiety among the study participants. Logistic regression analysis was used to identify predictors of depression and anxiety. RESULTS: The prevalence of depression and anxiety among the entire study participants was 23.8% and 13.1%, respectively. Anxiety was most prevalent across university students 21.5%, followed by healthcare professionals 11.3%, and general population 8.8%. Females among healthcare professionals and university students, divorced healthcare professionals, pulmonologists, and university students with history of chronic disease were at higher risk of developing depression. Females, divorced participants among the general population, and university students with history of chronic disease and those with high income (≥1,500 JD) were at higher risk of developing anxiety. CONCLUSIONS: During outbreaks, individuals are put under extreme stressful condition resulting in higher risk of developing anxiety and depression particularly for students and healthcare professionals. Policymakers and mental healthcare providers are advised to provide further mental support to these vulnerable groups during this pandemic.


title: Diminished COX-2/PGE(2)-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

text: Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble control and G6PD-knockdown (G6PD-kd) A549 cells upon tumor necrosis factor-α (TNF-α) stimulation. A decreased expression pattern of induced COX-2 and reduced production of downstream PGE(2) occurred upon TNF-α stimulation in G6PD-kd A549 cells compared with scramble control A549 cells. TNF-α-induced antiviral activity revealed that decreased COX-2 expression enhanced the susceptibility to coronavirus 229E infection in G6PD-kd A549 cells and was a result of the decreased phosphorylation levels of MAPK (p38 and ERK1/2) and NF-κB. The impaired inflammatory response in G6PD-kd A549 cells was found to be mediated through NADPH oxidase (NOX) signaling as elucidated by cell pretreatment with a NOX2-siRNA or NOX inhibitor, diphenyleneiodonium chloride (DPI). In addition, NOX activity with TNF-α treatment in G6PD-kd A549 cells was not up-regulated and was coupled with a decrease in NOX subunit expression at the transcriptional level, implying that TNF-α-mediated NOX signaling requires the participation of G6PD. Together, these data suggest that G6PD deficiency affects the cellular inflammatory response and the decreased TNF-α-mediated antiviral response in G6PD-kd A549 cells is a result of dysregulated NOX/MAPK/NF-κB/COX-2 signaling.


title: Examining health disparities and characteristics in general practice utilization: based on outpatient data from 2014 - 2018 in Shanghai

text: BACKGROUND: Since 2000, China has been developing primary care institutions to serve as the gateway to the healthcare system. However, the investment of resources in primary care institutions is not based on the actual medical demands of the public. This study analysed primary care utilization to provide targeted guidance for the improvement of primary healthcare delivery in China. METHODS: We extracted outpatient visit data from all community healthcare centres in Shanghai from 2014 to 2018. Diseases were then classified according to ICD-10 codes. The disease spectrum (frequency, proportion, rank) was stratified by sex, age, and region. RESULTS: Most primary care outpatients were female (58.20%), 60–79 years old (57.91%), and in suburban regions (62.18%). Chronic diseases accounted for the majority (91.41%). Hypertension, chronic ischaemic heart disease, diabetes, and acute upper respiratory tract infections were the top four disorders for primary care visits regardless of sex. In the group aged 0–18 years, symptoms, signs and abnormal clinical and laboratory findings not elsewhere classified accounted for 37.96% of the top 20 reasons. Acute upper respiratory tract infections were the most common diseases in the groups aged 0–18 (11.20%) and 19–39 (11.14%) years. However, hypertension was the most common disease in the group aged > 39 years old (> 20%). There were more outpatients with respiratory and digestive diseases in suburban areas than in urban areas. In addition, problems associated with medical equipment and other healthcare deficiencies were relatively more common in suburban areas (suburban: 4.13%, rank 5; urban: 2.29%, rank 10). CONCLUSIONS: To meet the patients’ needs and to develop the primary care system, the Shanghai government should focus on diseases with regionally high proportions. Disease diagnosis and treatment should be improved in the younger and suburban populations.


title: The isolation period should be longer: Lesson from a child infected with SARS‐CoV‐2 in Chongqing, China

text: In December 2019, COVID‐19 caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) outbroke in Wuhan, the capital city of Hubei province, China. The disease rapidly spread to other areas in China due to a huge population movement during the New Year Festival. Here, a 7‐year‐old child with SARS‐CoV‐2 infection in Chongqing, outside of Wuhan, Hubei province, was reported. This case suggested that children infected with SARS‐CoV‐2 are more likely to present milder manifestations than adults. The continuous positive real‐time reverse transcription‐polymerase chain reaction assay for SARS‐CoV‐2 in the child's throat swab sample indicated the isolation period for suspected child cases should be longer than 14 days.


title: Descriptive epidemiology of fatal respiratory outbreaks and detection of a human‐related metapneumovirus in wild chimpanzees (Pan troglodytes) at Mahale Mountains National Park, Western Tanzania

text: Over the past several years, acute and fatal respiratory illnesses have occurred in the habituated group of wild chimpanzees at the Mahale Mountains National Park, Tanzania. Common respiratory viruses, such as measles and influenza, have been considered possible causative agents; however, neither of these viruses had been detected. During the fatal respiratory illnesses in 2003, 2005 and 2006, regular observations on affected individuals were recorded. Cause‐specific morbidity rates were 98.3, 52.4 and 33.8%, respectively. Mortality rates were 6.9, 3.2 and 4.6%; all deaths were observed in infants 2 months–2 years 9 months of age. Nine other chimpanzees have not been seen since the 2006 outbreak and are presumed dead; hence, morbidity and mortality rates for 2006 may be as high as 47.7 and 18.5%, respectively. During the 2005 and 2006 outbreaks, 12 fecal samples were collected from affected and nonaffected chimpanzees and analyzed for causative agents. Analysis of fecal samples from 2005 suggests the presence of paramyxovirus, and in 2006 a human‐related metapneumovirus was detected and identified in an affected chimpanzee whose infant died during the outbreak. Our findings provide preliminary evidence that the causative agent associated with these illnesses is viral and contagious, possibly of human origin; and that, possibly more than one agent may be circulating in the population. We recommend that baseline health data be acquired and food wadge and fecal samples be obtained and bio‐banked as early as possible when attempting to habituate new groups of chimpanzees or other great apes. For already habituated populations, disease prevention strategies, ongoing health monitoring programs and reports of diagnostic findings should be an integral part of managing these populations. In addition, descriptive epidemiology should be a major component of disease outbreak investigations. Am. J. Primatol. 70: 755–765, 2008. © 2008 Wiley‐Liss, Inc.


title: Impact of the COVID-19 Pandemic on Quality of Life for Women with Ovarian Cancer

text: Abstract Purpose The COVID-19 pandemic has resulted in unprecedented challenges for the oncology community. For people living with cancer, treatments are interrupted, surgeries cancelled and regular oncology evaluations rescheduled. People with cancer and their physicians must balance plausible fears of COVID-19 and cancer treatment with the consequences of delaying cancer care. We aim to evaluate the experience of women with ovarian cancer during the COVID-19 pandemic. Methods Women with a current or prior diagnosis of ovarian cancer completed an online survey focusing on treatment interruptions and quality of life (QOL). QOL was measured with the Cancer Worry Scale and Hospital Anxiety and Depression Scale. The survey was distributed through survivor networks and social media. Univariate and multivariable linear regression analysis were utilized to evaluate the effect of participant characteristics on QOL survey scores. Results Six hundred and three women, from 41 states, visited the survey website between March 30 and April 13, 2020 and 555 (92.0%) completed the survey. The median age was 58 years (range 20-85). Two hundred and seventeen participants (43.3%) were in active treatment at the time of survey completion. One hundred and seventy-five participants (33%) experienced a delay in some component of their cancer care. Ten (26.3%) of the 38 participants scheduled for surgery experienced a delay and 18 (8.3%) of the 217 participants scheuled for nonsurgical cancer treatment. One hundred and thirty-three participants (24.0%) had a delayed physician appointment, 84 (15.1%) laboratory test and 53 (9.6%) cancer related imaging. Among the cohort, 88.6% (489) reported significant cancer worry, 51.4% (285) borderline or abnormal anxiety and 26.5% (147) borderline or abnormal depression. On univariate analysis, age less than 65 years, being scheduled for cancer treatment or cancer surgery, delay in oncology care, self-described as immunocompromised and use of telemedicine were all associated with higher levels of cancer worry. Higher anxiety scores were associated with age less than 65 years and self-described as immunocompromised. Higher depression scores were associated with age less than 65 years, being scheduled for cancer surgery, delay in oncology care, self-described as immunocompromised and use of telemedicine. On multivariable linear regression analysis, age less than 65 and being self-described as immunocompromised were independently predictive of greater cancer worry, anxiety and depression and delay in cancer care was predictive of anxiety and depression. Conclusions The COVID-19 crisis is impacting care of ovarian cancer patients: surgeries, treatments, scheduled physician appointments, laboratory tests and imaging are cancelled or delayed. Younger age, presumed immunocompromise and delay in cancer care were associated with significantly higher levels of cancer worry, anxiety and depression. Providers must work with patients to balance competing risks of COVID-19 and cancer, recognizing that communication is a critical clinical tool to improve quality of life in these times.


title: Maternal and neonatal outcomes associated with COVID-19 infection: A systematic review

text: BACKGROUND: COVID-19 has created an extraordinary global health crisis. However, with limited understanding of the effects of COVID-19 during pregnancy, clinicians and patients are forced to make uninformed decisions. OBJECTIVES: To systematically evaluate the literature and report the maternal and neonatal outcomes associated with COVID-19. SEARCH STRATEGY: PubMed, MEDLINE, and EMBASE were searched from November 1(st), 2019 and March 28(th), 2020. SELECTION CRITERIA: Primary studies, reported in English, investigating COVID-19-positive pregnant women and reporting their pregnancy and neonatal outcomes. DATA COLLECTION AND ANALYSIS: Data in relation to clinical presentation, investigation were maternal and neonatal outcomes were extracted and analysed using summary statistics. Hypothesis testing was performed to examine differences in time-to-delivery. Study quality was assessed using the ICROMS tool. MAIN RESULTS: Of 73 identified articles, nine were eligible for inclusion (n = 92). 67.4% (62/92) of women were symptomatic at presentation. RT-PCR was inferior to CT-based diagnosis in 31.7% (26/79) of cases. Maternal mortality rate was 0% and only one patient required intensive care and ventilation. 63.8% (30/47) had preterm births, 61.1% (11/18) fetal distress and 80% (40/50) a Caesarean section. 76.92% (11/13) of neonates required NICU admission and 42.8% (40/50) had a low birth weight. There was one indeterminate case of potential vertical transmission. Mean time-to-delivery was 4.3±3.08 days (n = 12) with no difference in outcomes (p>0.05). CONCLUSIONS: COVID-19-positive pregnant women present with fewer symptoms than the general population and may be RT-PCR negative despite having signs of viral pneumonia. The incidence of preterm births, low birth weight, C-section, NICU admission appear higher than the general population.


title: Study of interactions between actinomycin D and oligonucleotides by microchip electrophoresis and ESI-MS

text: In the present study, the interactions between actinomycin D (ActD) and single stranded DNA (ssDNA) 5′-CGTAACCAACTGCAACGT-3′ and a duplex stranded DNA (dsDNA) with this sequence were investigated by microchip-based non-gel sieving electrophoresis and electrospray ionization mass spectrometry (ESI-MS). The ssDNA was designed according to the conserved regions of open reading frame 1b (replicase 1B) following the Tor 2 SARS genome sequence of 15611-15593. The binding constants of the interactions between ActD and ssDNA/dsDNA were (8.3 ± 0.32) × 10(6) M(−1) (ssDNA) and (2.8 ± 0.02) × 10(5) M(−1) (dsDNA), respectively, calculated from microchip electrophoresis via Scatchard plot. The binding stoichiometries were 1:1 (single/1ActD molecule) and 1:2 (duplex/2ActD molecules) calculated from microchip electrophoresis, and the results were further verified by ESI-MS. The results obtained by these two methods indicated that ActD bound much more tightly to ssDNA used in this work than dsDNA. Furthermore, this is shown that the microchip-based non-gel sieving electrophoresis method is a rapid, highly sensitive and convenient method for the studies of interactions between DNA and small molecule drugs.


title: MERS coronavirus outbreak: Implications for emerging viral infections

text: Abstract In September 2012, a novel coronavirus was isolated from a patient who died in Saudi Arabia after presenting with acute respiratory distress and acute kidney injury. Analysis revealed the disease to be due to a novel virus which was named Middle East Respiratory Coronavirus (MERS-CoV). There have been several MERS-CoV hospital outbreaks in KSA, continuing to the present day, and the disease has a mortality rate in excess of 35%. Since 2012, the World Health Organization has been informed of 2220 laboratory-confirmed cases resulting in at least 790 deaths. Cases have since arisen in 27 countries, including an outbreak in the Republic of Korea in 2015 in which 36 people died, but more than 80% of cases have occurred in Saudi Arabia.. Human-to-human transmission of MERS-CoV, particularly in healthcare settings, initially caused a ‘media panic’, however human-to-human transmission appears to require close contact and thus far the virus has not achieved epidemic potential. Zoonotic transmission is of significant importance and evidence is growing implicating the dromedary camel as the major animal host in spread of disease to humans. MERS-CoV is now included on the WHO list of priority blueprint diseases for which there which is an urgent need for accelerated research and development as they have the potential to cause a public health emergency while there is an absence of efficacious drugs and/or vaccines. In this review we highlight epidemiological, clinical, and infection control aspects of MERS-CoV as informed by the Saudi experience. Attention is given to recommended treatments and progress towards vaccine development.


title: An improved nonchromatographic method for the purification of recombinant proteins using elastin-like polypeptide-tagged proteases

text: Abstract Proteins fused to the elastin-like polypeptide (ELP) tag can be selectively separated from crude cell extract without chromatography. To avoid the interference of the ELP tag on properties of the target protein, it is necessary to remove the ELP tag from target protein by protease digestion. Therefore, an additional chromatographic purification step is required to remove the proteases, and this is time- and labor-consuming. Here we demonstrate the utility of the ELP-tagged proteases for cleavage of ELP fusion proteins, allowing one-step removal of the cleaved ELP tag and ELP-tagged proteases without chromatography.


The Vascular Surgery Covid-19 Collaborative (VASCC)


title: The impact of the SARS‐CoV‐2 infection, with special reference to the haematological setting

text: SARS‐CoV‐2 is a disease known from a few months, caused by a recently arisen virus and, consequently, it is little known. The disease has a benign course in most infected subjects (children and young adults), is often symptomatic in adults over the age of 50 and often serious and life threatening in people with comorbidities and the elderly. The few data published on COVID‐19 in the blood‐oncology field report a serious clinical presentation, a serious course of the disease and a high mortality rate, as has also been reported for other cancer contexts. The current strategy for treating patients with SARS‐CoV‐2 includes antivirals that are effective against other viral infections and drugs that can moderate the cytokine storm. There is no specific vaccine and consequently all possible precautions must be taken to prevent SARS‐CoV‐2 infection in the areas of oncology, onco‐hematology, and bone marrow transplantation. In this reviewer's article, we report the information currently available on SARS‐CoV‐2 infection to help young doctors and hematologists to successfully manage patients with COVID‐19. This article is protected by copyright. All rights reserved.


title: Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

text: Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.


title: Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice

text: BACKGROUND: Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation. METHODS: Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined. RESULTS: The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal. CONCLUSION: Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.


Palliative Care in the time of COVID-19: Reflections from the frontline


Program and Abstracts for the 18th ICAR


title: Genome-wide host responses against infectious laryngotracheitis virus vaccine infection in chicken embryo lung cells

text: BACKGROUND: Infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) infection causes high mortality and huge economic losses in the poultry industry. To protect chickens against ILTV infection, chicken-embryo origin (CEO) and tissue-culture origin (TCO) vaccines have been used. However, the transmission of vaccine ILTV from vaccinated- to unvaccinated chickens can cause severe respiratory disease. Previously, host cell responses against virulent ILTV infections were determined by microarray analysis. In this study, a microarray analysis was performed to understand host-vaccine ILTV interactions at the host gene transcription level. RESULTS: The 44 K chicken oligo microarrays were used, and the results were compared to those found in virulent ILTV infection. Total RNAs extracted from vaccine ILTV infected chicken embryo lung cells at 1, 2, 3 and 4 days post infection (dpi), compared to 0 dpi, were subjected to microarray assay using the two color hybridization method. Data analysis using JMP Genomics 5.0 and the Ingenuity Pathway Analysis (IPA) program showed that 213 differentially expressed genes could be grouped into a number of functional categories including tissue development, cellular growth and proliferation, cellular movement, and inflammatory responses. Moreover, 10 possible gene networks were created by the IPA program to show intermolecular connections. Interestingly, of 213 differentially expressed genes, BMP2, C8orf79, F10, and NPY were expressed distinctly in vaccine ILTV infection when compared to virulent ILTV infection. CONCLUSIONS: Comprehensive knowledge of gene expression and biological functionalities of host factors during vaccine ILTV infection can provide insight into host cellular defense mechanisms compared to those of virulent ILTV.


Why transition matters as much as eradication: lessons from global polio surveillance


title: Highly sensitive detection of SARS-CoV-2 RNA by multiplex rRT-PCR for molecular diagnosis of COVID-19 by clinical laboratories

text: Abstract Background The detection of SARS-CoV-2 RNA by real-time reverse transcription–polymerase chain reaction (rRT-PCR) is used to confirm the clinical diagnosis of COVID-19 by molecular diagnostic laboratories. We developed a multiplex rRT-PCR methodology for the detection of SARS-CoV-2 RNA. Methods Three genes were used for multiplex rRT-PCR: the Sarbecovirus specific E gene, the SARS-CoV-2 specific N gene, and the human ABL1 gene as an internal control. Results Good correlation of Cq values was observed between the simplex and multiplex rRT-PCR methodologies. Low copies (<25 copies/reaction) of SARS-CoV-2 RNA were detected by the novel multiplex rRT-PCR method. Conclusion The proposed multiplex rRT-PCR methodology will enable highly sensitive detection of SARS-CoV-2 RNA, reducing reagent use and cost, and time required by clinical laboratory technicians.


title: A Rare Case of Immune Thrombocytopenic Purpura Secondary to COVID‐19

text: Coronavirus Disease 2019 (COVID‐19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). After its first occurrence in Wuhan of China from December 2019, COVID‐19 rapidly spread around the world. Studies have shown that coagulation dysfunction is one of the important reason causing death of COVID‐19 patients and appeared in many patients. However, cases of COVID‐19 with immune thrombocytopenic purpura were very rare. Here, a patient with immune thrombocytopenic purpura in Huoshenshan Hospital (Wuhan, China) was reported, whose laboratory data, clinical treatment and hospital outcome was described in this study. Fortunately, immune thrombocytopenic purpura with COVID‐19 of the patient was diagnosed and treated in time and cured eventually. This case illustrates the need to be vigilant for complications associated with COVID‐19. This article is protected by copyright. All rights reserved.


title: Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China

text: OBJECTIVE: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.


Prévention de la Covid-19 après le confinement : pour un retour rapide « à la vie d’avant »


title: The interplay between endoplasmic reticulum stress and inflammation

text: Endoplasmic reticulum (ER) stress may be both a trigger and consequence of chronic inflammation. Chronic inflammation is often associated with diseases that arise because of primary misfolding mutations and ER stress. Similarly, ER stress and activation of the unfolded protein response (UPR) is a feature of many chronic inflammatory and autoimmune diseases. In this review, we describe how protein misfolding and the UPR trigger inflammation, how environmental ER stressors affect antigen presenting cells and immune effector cells, and present evidence that inflammatory factors exacerbate protein misfolding and ER stress. Examples from both animal models of disease and human diseases are used to illustrate the complex interactions between ER stress and inflammation, and opportunities for therapeutic targeting are discussed. Finally, recommendations are made for future research with respect to the interaction of ER stress and inflammation.


title: The pathologic autopsy of coronavirus disease 2019 (COVID-2019) in China: a review

text: The coronavirus disease 2019 (COVID-2019) emerged in Wuhan, China, has rapidly spread to many countries across all six WHO regions. However, its pathobiology remains incompletely understood and many efforts are underway to study it worldwide. To clarify its pathogenesis to some extent, it will inevitably require lots of COVID-2019-associated deaths at pathologic autopsy. Pathologists from all over the world have raised concern with pathologic autopsy relating to COVID-2019. The issue of whether a person dies from COVID-2019 infection or not always is an ambiguous problem in some cases, and ongoing epidemiology from China may shed light on it. This review retrospectively summarizes the research status of pathologic autopsy in COVID-2019 in China, which will be important for the cause of death, prevention, control and clinical strategies of COVID-2019. Moreover, it points out several challenges at autopsy. We believe pathological studies from China enable to correlate clinical symptoms and pathological features of COVID-2019 for doctors and provide an insight into COVID-2019 disease.


title: The Demand for Health Care

text: Health-care demand analysis provides information that policy makers can use to improve a population's health. Since demand estimates identify determinants of health-care utilization, the estimates could be used to design policies to improve access to health facilities. However, evidence on health-care demand alone is insufficient to implement policies aimed at improving health. To facilitate implementation of such interventions, it is necessary to link health-care utilization to health status. This article provides an exposition of a model that links health-care demand to health production. Implications of the model in settings of information imperfections and lack of self-control in health-care markets are analyzed.


title: Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.


title: Delivery of RNAi mediators

text: Delivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody‐mediated delivery techniques, it is possible to rationally design delivery vehicles that circulate in the blood stream and are specifically delivered into target organs. If the targeting moiety is designed to contain the cargo of an RNAi mediator without impacting its paratope, directed delivery can be achieved. In this article, we review the state of art in delivery technology for RNA mediators and address how this technique could soon be used to enhance the efficacy of the numerous small RNA therapeutic programs currently under evaluation. Copyright © 2010 John Wiley & Sons, Ltd. 1.. Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action; 2.. RNA Methods > RNA Analyses in Cells; 3.. RNA in Disease and Development > RNA in Disease.


title: Multiplex real-time PCR for prompt diagnosis of an outbreak of human parainfluenza 3 virus in children with acute leukemia

text: INTRODUCTION: Human parainfluenza virus type 3 (HPIV-3) causes significant morbimortality in immunocompromised patients. Outbreaks of severe pneumonitis have been previously described in this setting. MATERIALS AND METHODS: Retrospective observational study in children diagnosed with acute leukemia and a documented HPIV-3 infection in the context of a nosocomial outbreak occurred in a single center. RESULT: During summer 2012, an HPIV-3 infection was detected in six hospitalized children with acute leukemia. All the patients had respiratory symptoms and one of them suffered from parotitis. CONCLUSION: Early diagnoses using multiplex real-time polymerase chain reaction (PCR) let us control this outbreak. A phylogenetic analysis confirmed person-to-person transmission of a single HPIV-3 variant.


title: Tacrolimus trough levels before, during and after jejunostomy in a liver transplant patient: A case report

text: Summary Although the feasibility of oral tacrolimus administration in the presence of jejunostomy has already been reported, few studies monitoring tacrolimus trough blood levels have been analyzed in detail, either during or after a jejunostomy closure. We report on our experience with a 34-year-old patient who underwent liver transplantations, with a proximal jejunostomy constructed a few days prior to the second transplantation. He was administered tacrolimus by a predominantly oral route, and less frequently received it by jejunostomy. The aim of this paper is to discuss this administration strategy and whether a different method could have been more suitable. This case report highlights that during the jejunostomy period, the tacrolimus doses that were required to maintain trough concentrations within the therapeutic range were four times higher than those administered after the closure of the jejunostomy. We observed an increase in the Dose-Normalized Trough Concentration (DNTC) values when tacrolimus was administered for 4 consecutive days by jejunostomy as compared to oral administration, indicating that the relative bioavailability of tacrolimus increased. Moreover, when returning to oral administration, the subsequent DNTC value was halved, highlighting a reduction in the tacrolimus bioavailability. Thus, in such a case, administration by jejunostomy could be more appropriate.


title: Antiviral activity of interleukin-11 as a response to porcine epidemic diarrhea virus infection

text: Interleukin-11 (IL-11), a well-known anti-inflammatory factor, provides protection from intestinal epithelium damage caused by physical or chemical factors. However, little is known of the role of IL-11 during viral infections. In this study, IL-11 expression at mRNA and protein levels were found to be high in Vero cells and the jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, while IL-11 expression was found to be positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) was found to suppress PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 was found to inhibit viral infection by preventing PEDV-mediated apoptosis of cells by activating the IL-11/STAT3 signaling pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggest that IL-11 is a newfound PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential of IL-11 to be used as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.


Tromboembolia pulmonar aguda y enfermedad por coronavirus (COVID-19): ¿una asociación frecuente en pacientes graves?


title: Que reste t-il de la microscopie électronique pour le diagnostic anatomopathologique en 2010 ?

text: In the last decades, several ancillary methods, such as immunohistochemistry and molecular biology techniques, have increased the possibilities for the diagnosis and to evaluate the prognosis of lesions observed in a laboratory of pathology. Conversely, the impact of another method largely used a couple of years ago in a laboratory of pathology, the electron microscopy (EM), is currently limited. EM is a difficult, quite expensive and long method, which requires technicians with a high qualification. Therefore, EM is currently rarely available at the hospital in a laboratory of pathology and is essentially established in research centers. However, EM is still an essential tool for the surgical pathologist. This method allows in some circumstances to confirm or, more rarely, to make the diagnosis of a couple of tissular and cellular lesions observed in human pathology. EM is also an interesting method to better understand the etiopathogenesis of emerging human diseases, in particular of emerging infectious diseases. In this review, we report the main indication of EM in human pathology, we lay special emphasize in certain infectious diseases and neoplasia.


title: SYNCRIP (Synaptotagmin-Binding, Cytoplasmic RNA-Interacting Protein) Is a Host Factor Involved In Hepatitis C virus RNA Replication

text: Hepatitis C virus (HCV) RNA replication requires viral nonstructural proteins as well as cellular factors. Recently, a cellular protein, synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as NSAP1, was found to bind HCV RNA and enhance HCV IRES-dependent translation. We investigate whether this protein is also involved in the HCV RNA replication. We found that SYNCRIP was associated with detergent-resistant membrane fractions and colocalized with newly-synthesized HCV RNA. Knock-down of SYNCRIP by siRNA significantly decreased the amount of HCV RNA in the cells containing a subgenomic replicon or a full-length viral RNA. Lastly, an in vitro replication assay after immunodepletion of SYNCRIP showed that SYNCRIP was directly involved in HCV RNA replication. These findings indicate that SYNCRIP has dual functions, participating in both RNA replication and translation in HCV life cycle.


ABSTRACTS From Concurrent Meetings of The Southern Poultry Science Society, 22nd Annual Meeting The Southern Conference on Avian Diseases, 42nd Annual Meeting January 15 & 16, 2001


title: Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis

text: INTRODUCTION: Within this large‐scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID‐19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed‐effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID‐19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID‐19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid‐19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X‐ray. The mortality rate in COVID‐19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID‐19 confirmed cases is lower than in SARS‐ and MERS‐infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.


title: The Neglected Role of Physical Education Participation on Suicidal Ideation and Stress in High School Adolescents from South Korea

text: Adolescents are at high risk of suicidal ideation and stress. This study aimed to investigate how physical education participation predicts suicidal ideation and stress in South Korean high school students. Data from the Twelfth Korea Youth Risk Behaviour Web-Based Survey 2016 (KYRBS) were used for analyses. Two multiple logistic regressions were performed to determine the influence of selected factors on suicidal ideation and stress (model 1: subjective health, social support, body mass index, academic achievement, perceived economic status of family, and physical education participation; model 2: adjusting for school type and year). Model 2 revealed negative associations between subjective health, academic achievement, perceived economic status of family, social support, physical education participation (≥2 times/weekly), and suicidal ideation for male students. Female students exhibited negative associations between subjective health, social support, and academic achievement, along with a positive association between body mass index and suicidal ideation. For both genders, stress was negatively associated with subjective health, social support, academic achievement, perceived economic status of family, and physical education participation (≥2 times/weekly). These findings suggest that participating in physical education can mitigate the risk of suicidal ideation and stress among high school students.


Management of Graves’ hyperthyroidism and orbitopathy in time of COVID-19 pandemic


Mechanisms and Consequences of Virus Persistence in the Human Nervous System


title: The pig as a mixing vessel for influenza viruses: Human and veterinary implications

text: Influenza A viruses are highly infectious respiratory pathogens that can infect many species. Birds are the reservoir for all known influenza A subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. Because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the “mixing vessel” theory. There is no direct evidence that the reassortment events culminating in the 1918, 1957 or 1968 pandemic influenza viruses originated from pigs. Genetic reassortment among avian, human and/or swine influenza virus gene segments has occurred in pigs and some novel reassortant swine viruses have been transmitted to humans. Notably, novel reassortant H2N3 influenza viruses isolated from the US pigs, most likely infected with avian influenza viruses through surface water collected in ponds for cleaning barns and watering animals, had a similar genetic make-up to early isolates (1957) of the H2N2 human pandemic. These novel H2N3 swine viruses were able to cause disease in swine and mice and were infectious and highly transmissible in swine and ferrets without prior adaptation. The preceding example shows that pigs could transmit novel viruses from an avian reservoir to other mammalian species. Importantly, H2 viruses pose a substantial risk to humans because they have been absent from mammalian species since 1968 and people born after 1968 have little preexisting immunity to the H2 subtype. It is difficult to predict which virus will cause the next human pandemic and when that pandemic might begin. Importantly, the establishment and spread of a reassorted mammalian-adapted virus from pigs to humans could happen anywhere in the world. Therefore, both human and veterinary research needs to give more attention to potential cross-species transmission capacity of influenza A viruses.


Appointment Characteristics in an Allergy/Immunology Practice in the Immediate Aftermath of COVID-19 Restrictions


title: Identification of six new polymorphisms in the human coronavirus 229E receptor gene (aminopeptidase N/CD13)

text: Abstract Objective: Human aminopeptidase N (APN/CD13/ANPEP) has been identified as the receptor for human coronavirus (HCoV) 229E. In this study, we analyzed the region of the APN gene that encodes a stretch of amino acid residues, essential for its HCoV-229E receptor function (amino acids 260–353). Methods: Full-length APN exon 3, intron 3 and exon 4, was PCR-amplified and sequenced in DNA samples from 100 unrelated Caucasian Belgian healthy volunteers. Results: We identified seven polymorphisms, including four intron 3 and three exon 4 variations. Apart from the already known C956T exon 4 mutation, the six other polymorphisms have not yet been described. The most prevalent APN variations in this population (C956T leading to an alanine to valine substitution, G978T, G987A and intron3-C389T) always occurred together at an allele frequency of 8.5%. Haploid DNA sequencing demonstrated the presence of these four variations on the same allele. Three polymorphisms in intron 3, intron3-G395C, intron3-C86T, and intron3-C429T, were identified with an allele frequency of 3.5%, 1% and 0.5% respectively. Five haplotypes were identified in the population of 100 individuals. Conclusion: These results demonstrate that there is a relatively broad spectrum of variations in the APN domain critical for coronavirus binding. The nucleotide sequence reported here has been submitted to the GenBank database with the following accession number: AF527789.


Lost ground: Female academics face an uphill battle in post‐pandemic world


title: Detection and molecular characterization of canine circovirus circulating in northeastern China during 2014–2016

text: Canine circovirus (canine CV) is an etiological agent associated with diarrhea, hemorrhagic gastroenteritis and vasculitis. Although canine CV has been identified and characterized in southern China in recent years, its epidemiology in other regions of China and its precise molecular characteristics have not been examined. In this study, we examined 141 fecal specimens collected from domestic dogs with or without diarrhea in Heilongjiang province, Northeastern China, during 2014 to 2016. A total of 18 out of 141 samples were found to be positive for canine CV by real-time quantitative PCR. In the diarrhea samples, canine CV was detected in coinfections with canine parvovirus 2. More importantly, two different canine CV strains were detected in one sample. Five canine CV genomes were successfully amplified. Sequence analysis showed that there were two unique amino acid changes in the Rep protein (N39S in the K1 strain, and T71A in the XF16 strain). Phylogenetic analysis indicated that canine CV could be divided into four genotypes, and specific nucleotide mutations could be used for confirming the four genotypes. Moreover, recombination analysis revealed that a total of eight recombination events were found in five genomic sequences. Molecular evolution analysis showed that the canine CV has been under purifying selection. This study provides evidence that at least three genotypes of canine CV are co-circulating in China. Continuous epidemiological surveillance is therefore necessary to understand their importance for the evolution of canine CV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04433-4) contains supplementary material, which is available to authorized users.


title: Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein

text: Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide, that possesses both enteric and respiratory tropism. The ability to replicate in the enteric tract directly correlates with virulence, as TGEVs with an exclusive respiratory tropism are attenuated. The tissue tropism is determined by spike (S) protein, although the molecular bases for enteric tropism remain to be fully characterized. Both pAPN and sialic acid binding domains (aa 506–655 and 145–155, respectively) are necessary but not sufficient for enteric tract infection. Using a TGEV infectious cDNA and enteric (TGEV-SC11) or respiratory (TGEV-SPTV) isolates, encoding a full-length S protein, a set of chimeric recombinant viruses, with a sequential modification in S protein amino terminus, was engineered. In vivo tropism, either enteric, respiratory or both, was studied by inoculating three-day-old piglets and analyzing viral titers in lung and gut. The data indicated that U655>G change in S gene (S219A in S protein) was required to confer enteric tropism to a respiratory virus that already contains the pAPN and sialic acid binding domains in its S protein. Moreover, an engineered virus containing U655>G and a 6 nt insertion at position 1124 (Y374-T375insND in S protein) was genetically stable after passage in cell cultures, and increased virus titers in gut by 1000-fold. We postulated that the effect of these residues in enteric tropism may be mediated by the modification of both glycosaminoglycan binding and S protein structure.


title: Complete genome comparison of duck hepatitis virus type 1 parental and attenuated strains

text: Two complete duck hepatitis virus type 1 (DHV-1) genomes, strain SY5 and its chicken embryos passage descendent vaccine strain ZJ-A, were compared and analyzed in order to identify possible sites of attenuation. Of the 205 nucleotide changes, 22 resulted in sense mutations, 174 produced nonsense mutations. Besides, there are 7 consistent nucleotides substitutions in 5′UTR and 2 in 3′UTR. Three of these 22 sense mutations resided in VP0, 6 exists in VP1, one exists in VP3, 3 exists in 2A2, 3 exists in 2C, one was detected in 3B and 5 was in 3D. These results suggested that VP0, VP1, 3D, and 5′/3′UTR may contribute to the attenuation of DHV-1 in chicken/duck/embryos. The results provide a genetic basis for future manipulation of a DHV-1 infectious clone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-012-0767-0) contains supplementary material, which is available to authorized users.


title: The Challenges of COVID‐19 for Divorcing and Post‐divorce Families

text: COVID‐19 and the accompanying procedures of shelter‐in‐place have had a powerful effect on all families but have additional special meanings in the context of families contemplating divorce, divorcing, or carrying out postdivorce arrangements. This paper explores those special meanings for these families. It also offers suggestions for couple and family therapists involved in helping these families during the time of COVID‐19.


title: Infection of a calf with the enteric coronavirus strain Paris

text: A tissue-culture-grown enteric coronavirus infected the whole of the gastrointestinal tract and caused enteritis and diarrhoea in a 10-day-old gnotobiotic Friesian calf. Diarrhoea occurred 2 days after inoculation and excretion of virus in faeces and rectal swabs increased until necropsy at 3 days. Virus growth, as detected by indirect immunofluorescence, virus isolation, and thin section electron microscopy, was most extensive in the epithelium of the colon and rectum at 3 days after inoculation. No virus was detected in other organs or in the pleural, peritoneal and oropharyngeal cavities. The origin and host specificity of this coronavirus is discussed.


title: The 2009 influenza A (H1N1) pandemic: Management and vaccination strategies in The Netherlands

text: Prior to 2009, The Netherlands had prepared itself extensively for a potential pandemic. Multidisciplinary guidelines had been drafted to control transmission and limit adverse outcomes for both a phase of early incidental introduction and for a phase with widespread transmission. The Ministry of Health had ensured a supply and distribution schedule for antivirals and negotiated a contract for vaccine purchases. During the pandemic, existing surveillance was expanded, the established infectious disease response structure was activated, and the previously prepared protocols for communication, diagnostics, use of antivirals, and vaccination implementation were operationalized and implemented. When the pandemic turned out to be less severe than many had anticipated, risk communication and rapid modification of guidelines and communication became a major challenge. Antivirals and pandemic vaccines were reserved for those at high risk for severe outcomes only. Overall, the impact of the pandemic was comparable to the impact of an average seasonal influenza epidemic, but with a shift in (severe) outcomes from the very young and elderly toward young adults. Established prepared protocols enabled timely coordinated responses. In preparing for the worst, sufficient attention must be given to preparing for a mild scenario as well.


title: Triaging advanced GI endoscopy procedures during the COVID-19 Pandemic: consensus recommendations using the Delphi method

text: Abstract Background and Aims There remains a lack of consensus on which gastrointestinal endoscopic procedures should be performed during the COVID-19 pandemic, and which procedures could be safely deferred without significantly impacting outcomes. Methods We selected a panel of 14 expert endoscopists. We identified 41 common indications for advanced endoscopic procedures from the ASGE Appropriate Use of GI Endoscopy guidelines. Using a modified Delphi method, we first achieved consensus on patient-important outcome for each procedural indication. Panelists prioritized consensus patient-important outcome when categorizing each indication into one of the following 3 procedural time periods: (1) time-sensitive emergent (schedule within 1 week), (2) time-sensitive urgent (schedule within 1 to 8 weeks), and (3) non-time sensitive (defer for >8 weeks and then reassess the timing). Three anonymous rounds of voting were allowed before attempts at consensus were abandoned. Results All 14 invited experts agreed to participate in the study. The prespecified consensus threshold of 51% was achieved for assigning patient-important outcome/s to each advanced endoscopy indication. The prespecified consensus threshold of 66.7% was achieved for 40 out of 41 advanced endoscopy indications in stratifying them into 1 of 3 procedural time periods. For 12 out of 41 indications 100% consensus, and for 20 out of 41 indications 75% to 99% consensus was achieved. Conclusions By using a Modified Delphi method that prioritized patient-important outcomes, we developed consensus recommendations on procedural timing for common indications for advanced endoscopy. These recommendations and the structured decision framework provided by our study can inform decision-making as endoscopy services are reopened.


title: The effect of the “stay‐at‐home” policy on requests for dermatology outpatient clinic visits after the COVID‐19 outbreak

text: The Coronavirus Disease 2019 (COVID‐19) emerged late in Turkey but it showed a rapid progression later. We aimed to investigate the changes in the number of patients who requested a dermatology outpatient clinic visit due to the increased social and medical burden caused by COVID‐19 in Turkey during the first days of the pandemic. We also examined the most common dermatologic diseases diagnosed during the COVID‐19 outbreak. A statistically significant negative correlation was found between the number of COVID‐19 patients in the country and the number of patients requesting a dermatology outpatient clinic visit in the secondary and tertiary care hospitals during self‐quarantine. In the first 10 days after the COVID‐19 outbreak, acne (28.2%), urticaria (12.8%), scabies (12.8%), irritant contact dermatitis (10.3%), and xerosis cutis (10.2%) were the most common diseases seen in the dermatology clinic at the secondary care hospital, while acne (23.3%), warts (5.4%), seborrheic dermatitis (4.5%), urticaria (3.8%), and psoriasis (3.32%) were the most common diseases seen in the dermatology clinic at the tertiary care hospital. This is our first study on the frequency and nature of outpatient dermatology visits during this novel coronavirus pandemic. Understanding the trends and impacts of dermatologic diseases on patients and health systems during this pandemic will allow for better preparation of dermatologists in the future.


title: Membrane dynamics associated with viral infection

text: Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease. © 2015 The Authors Reviews in Medical Virology Published by John Wiley & Sons, Ltd.


title: The COVID-19 pandemic from an ophthalmologist’s perspective

text: Abstract The current COVID-19 pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how SARS-Cov2 affects the eye and discuss implications for ophthalmologists.


Molecular Biology: Control of Messenger Synthesis


title: Comparison of a fimbrial versus an autotransporter display system for viral epitopes on an attenuated Salmonella vaccine vector

text: Attenuated Salmonella have been used as vectors to deliver foreign antigens as live vaccines. We have previously developed an efficient surface-display system by genetically engineering 987P fimbriae to present transmissible gastroenteritis virus (TGEV) C and A epitopes for the induction of anti-TGEV antibodies with a Salmonella vaccine vector. Here, this system was compared with an autotransporter protein surface display system. The TGEV C and A epitopes were fused to the passenger domain of the MisL autotransporter of Salmonella. Expression of both the MisL- and 987P subunit FasA-fusions to the TGEV epitopes were under the control of in vivo-induced promoters. Expression of the TGEV epitopes from the Salmonella typhimurium CS4552 (crp cya asd pgtE) vaccine strain was greater when the epitopes were fused to MisL than when they were fused to the 987P FasA subunit. However, when BALB/c mice were orally immunized with the Salmonella vector expressing the TGEV epitopes from either one of the fusion constructs or both together, the highest level of anti-TGEV antibody was obtained with the 987P-TGEV immunogen-displaying vector. This result suggested that better immune responses towards specific epitopes could be obtained by using a polymeric display system such as fimbriae.


Letter to the Editor: Kim, S-W., Su, K-P. (2020) Using psychoneuroimmunity against COVID-19, Brain, Behavior, and Immunity (2020), doi: https://doi.org/10.1016/j.bbi.2020.03.025


title: Early experience with influenza A H1N109 in an Australian intensive care unit

text: Summary Influenza is a common seasonal viral infection that affects large numbers of people. In early 2009, many people were admitted to hospitals in Mexico with severe respiratory failure following an influenza-like illness, subtyped as H1N1. An increased mortality rate was observed. By June 2009, H1N1 was upgraded to pandemic status. In June–July, Australian ICUs were experiencing increased activity due to the influenza pandemic. While hospitals implemented plans for the pandemic, the particularly heavy demand to provide critical care facilities to accommodate an influx of people with severe respiratory failure became evident and placed a great burden on provision of these services. This paper describes the initial experience (June to mid September) of the pandemic from the nursing perspective in a single Australian ICU. Patients were noted to be younger with a higher proportion of women, two of whom were pregnant. Two patients had APACHE III comorbidity. Of the 31 patients admitted during this period, three patients died in ICU and one patient died in hospital. Aerosol precautions were initiated for all patients. The requirement for single room accommodation placed enormous demands for bed management in ICU. Specific infection control procedures were developed to deal with this new pandemic influenza.


title: WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13–14 May 2009()

text: In May 2009, WHO convened a meeting of Working Group on Technical Specifications for Manufacturing and Evaluating Yellow Fever (YF) Vaccines, Geneva, Switzerland to initiate revision of the WHO Recommendations (formerly, Requirements) for YF vaccine published in WHO Technical Report Series number 872 (1998). The Working Group, consisting of experts from academia, industry, national regulatory authorities and national control laboratories, reviewed the latest issues of safety, efficacy and quality of YF vaccines and agreed that (i) the revision should focus on live attenuated YF vaccine virus 17D lineage; and that (ii) nonclinical and clinical guidelines for new vaccines prepared from 17D lineage be developed.


title: Neurological Causes of Diaphragmatic Paralysis in 11 Alpacas (Vicugna pacos)

text: Background: Diaphragmatic paralysis is a relatively uncommon medical condition in animals not reported in alpacas. Objectives: Describe the signalment, physical examination, diagnostic testing, clinical, and histopathologic findings related to diaphragmatic paralysis in alpacas. Animals: Eleven alpacas with spontaneous diaphragmatic paralysis. Methods: A retrospective study examined medical records from a 10‐year period and identified 11 alpacas with confirmed diaphragmatic paralysis admitted to Washington State University and Colorado State University Veterinary Teaching Hospitals between September 2003 and October 2009. Results: The 11 alpacas ranged in age from 2 to 12 months. Fluoroscopic imaging confirmed the presence of bilateral diaphragmatic paralysis in the 7 alpacas that were imaged. Arterial blood gas analyses showed hypercapnea, hypoxemia, and low oxygen saturation. Seven alpacas died or were euthanized between 2 and 60 days after onset of respiratory signs. Histopathologic examination of tissues found phrenic nerve degeneration in the 6 alpacas that were necropsied and additional long nerves examined demonstrated degeneration in 2 of these animals. Two animals had spinal cord lesions and 2 had diaphragm muscle abnormalities. No etiologic agent was identified in the alpacas. Conclusions and Clinical Importance: The etiology for diaphragmatic paralysis in these alpacas is unknown. A variety of medical treatments did not appear to alter the outcome.


title: 14 Climate change and infectious diseases

text: Publisher Summary The worldwide upturn in the occurrence of both new (emerging) and reemerging or spreading infectious diseases highlights the importance of underlying environmental and social conditions as determinants of the generation, spread, and impact of infectious diseases in human populations. Human ecology is undergoing rapid transition. This encompasses urbanization, rising consumerism, changes in working conditions, population aging, marked increases in mobility, changes in culture and behavior, evolving health-care technologies, and other factors. Global climate change is becoming a further, and major, large-scale influence on the pattern of infectious disease transmission. It is likely to become increasingly important over at least the next halfcentury, as the massive, highinertial, and somewhat unpredictable process of climate change continues. The many ways in which climate change does and will influence infectious diseases are subject to a plethora of modifying influences by other factors and processes: constitutional characteristics of hosts, vectors and pathogens; the prevailing ambient conditions; and coexistent changes in other social, economic, behavioral, and environmental factors. This global anthropogenic process, climate change, along with other unprecedented global environmental changes, is beginning to destabilize and weaken the planet's life-support systems. Infectious diseases, unlike other diseases, depend on the biology and behavior—each often climate-sensitive—of two or more parties. Hence, these diseases will be particularly susceptible to changes as the world's climate and its climate-sensitive geochemical and ecological systems undergo change over the coming decades.