title: Management factors associated with bovine respiratory disease in preweaned calves on California dairies: The BRD 100 study

text: ABSTRACT The objective of this cross-sectional study was to determine how management practices on California dairies may be associated with bovine respiratory disease (BRD) in preweaned calves. A convenience sample of 100 dairies throughout California, providing a study population of 4,636 calves, were visited between May 2014 and April 2016. During each farm visit, in-person interviews with the herd manager or calf caretaker were conducted to collect information about herd demographics, maternity pen, colostrum and calf management, herd vaccinations, and dust abatement. A random sample of preweaned calves was identified and evaluated for the presence of BRD using a standardized tool. A survey-adjusted generalized linear mixed model with a logit link function was fitted with calf as the unit of analysis and dairy as the random effect. Mean study herd size (±SE) was 1,718 (±189.9) cows. Survey-adjusted estimates of breed types in the sample were 81.6% (±0.6) Holstein, 13.1% (±0.4) Jersey, and 5.3% (±0.5) crossbred or other purebred breeds, and calf sex proportions were 73.8% (±1.0) female and 26.2% (±1.0) male. Overall survey-adjusted BRD prevalence in the study herds was 6.91% (±0.69). Housing factors positively associated with BRD were metal hutches compared with wood hutches [odds ratio (OR) = 11.19; 95% confidence interval (CI) = 2.80–44.78], calf-to-calf contact in calves >75 d of age (OR = 9.95, 95% CI = 1.50–65.86), feeding Holstein calves <2.84 L of milk or replacer per day (OR = 7.16, 95% CI = 1.23–41.68), and lagoon water used for flushing manure under hutches compared with no flush (OR = 12.06, 95% CI = 1.93–75.47). Providing extra shade over hutches (OR = 0.08; 95% CI = 0.02–0.37), feeding calves at least 90% saleable milk (OR = 0.27, 95% CI = 0.13–0.54) or pasteurized milk (OR = 0.10; 95% CI = 0.03–0.36), and feeding >5.68 L of milk or replacer per day to Jersey calves (OR = 0.04; 95% CI = 0.01–0.28) were negatively associated with BRD. Our study identified management practices on California dairies with variability and that may contribute to differences in BRD prevalence, which will be incorporated into a risk-assessment tool to control and prevent BRD in preweaned dairy calves.


title: Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein–lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.


title: Inhibition of alphavirus infection in cell culture and in mice with antisense morpholino oligomers

text: The genus Alphavirus contains members that threaten human health, both as natural pathogens and as potential biological weapons. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) enter cells readily and can inhibit viral replication through sequence-specific steric blockade of viral RNA. Sindbis virus (SINV) has low pathogenicity in humans and is regularly utilized as a model alphavirus. PPMO targeting the 5′-terminal and AUG translation start site-regions of the SINV genome blocked the production of infectious SINV in tissue culture. PPMO designed against corresponding regions in Venezuelan equine encephalitis virus (VEEV) were likewise found to be effective in vitro against several strains of VEEV. Mice treated with PPMO before and after VEEV infection were completely protected from lethal outcome while mice receiving only post-infection PPMO treatment were partially protected. Levels of virus in tissue samples correlated with animal survival. Uninfected mice suffered no apparent ill-effects from PPMO treatment. Thus, PPMO appear promising as candidates for therapeutic development against alphaviruses.


title: In vitro inhibition of coronavirus replications by the traditionally used medicinal herbal extracts, Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, and Phellodendron cortex

text: Abstract Background A search for new anti-coronaviral drugs to treat coronaviral infections was motivated by an outbreak of severe acute respiratory syndrome (SARS). Objectives In order to find drugs that treat coronavirus infections, including SARS, we screened traditional medicinal herbal extracts and evaluated their antiviral activities on coronavirus replication. Study design We employed a plaque assay to evaluate the effect of 22 medicinal herbal extracts on virus replication. We determined the 50% effective concentration (EC50) of each extract that was necessary to inhibit the replication of mouse hepatitis virus A59 (MHV-A59); we also determined 50% cytotoxic concentrations (CC50) for each extract. Northern and Western blot analyzes were performed to investigate antiviral activity in MHV-infected DBT cells, including virus entry, viral RNA and protein expression, and virus release. Coronavirus specific inhibition was also demonstrated using porcine epidemic diarrhea virus (PEDV). Results Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, Phellodendron cortex and Sophora subprostrata radix decreased the MHV production and the intracellular viral RNA and protein expression with EC50 values ranging from 2.0 to 27.5μg/ml. These extracts also significantly decreased PEDV production and less dramatically decreased vesicular stomatitis virus (VSV) production in vitro. Conclusions The extracts selected strongly inhibited MHV replication and could be potential candidates for new anti-coronavirus drugs.


title: Atherosclerotic spontaneous coronary artery dissection (A-SCAD) in a patient with COVID-19: case report and possible mechanisms

text: BACKGROUND: Spontaneous coronary artery dissection (SCAD) may be atherosclerotic (A-SCAD) or non-atherosclerotic (NA-SCAD) in origin. Contemporary usage of the term ‘SCAD’ is typically synonymous with NA-SCAD. COVID-19 could induce a vascular inflammation localized in the coronary adventitia and periadventitial fat and contribute to the development of an A-SCAD of a vulnerable plaque in a susceptible patient. CASE SUMMARY: In this report we describe a case of a COVID-19 patient with past cardiac history of CAD who was admitted for acute coronary syndrome (ACS). Coronary angiography demonstrated the culprit lesion in the proximal LAD that presented with a very complex and unusual morphology, indicative of an A-SCAD. The diagnosis of A-SCAD was supported by the presence of a mild stenosis in the same coronary segment in the last angiogram performed 3 years previously. He was successfully treated by PCI, had a favourable course of the COVID-19 with no symptoms of pneumonia, and was discharged from the hospital after two negative tests for SARS-CoV-2. DISCUSSION: A higher index of suspicion of A-SCAD is needed in patients with suspected or confirmed COVID-19 presenting with ACS. The proposed approach with ‘thrombolysis first’ for treating STEMI patients with suspected or confirmed COVID-19 infection could be unsafe in the case of underlying A-SCAD.


title: Circulating endocannabinoid concentrations in grieving adults

text: Bereavement is one of the most intense, distressing, and traumatic events an elderly person will experience. The symptom responses to bereavement vary, particularly during the first year. However, the neurobiology underlying the symptom variance in grief is poorly understood. The endocannabinoid signaling (ECS) system is stress-responsive; mounting evidence implicates abnormalities in the central ECS system could contribute to psychopathology. The current study aimed to investigate the hypothesis that the ECS is abnormal in grief, using circulating eCB concentrations as a biomarker of central ECS. A predominantly older sample of grief participants, within 13 months following the death of a loved one, and healthy comparison (HC) participants were studied. Associations of circulating eCBs with symptom variance in grievers were also examined. A total of 61 (grief: n = 44; HC: n = 17) adults completed cross-sectional clinical assessments and a fasting blood draw. Assessments included the Inventory of Complicated Grief scale; the 17-item Hamilton Depression Rating Scale; and the Hamilton Anxiety scale. Serum eCB concentrations (i.e., N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) were quantified using isotope dilution, liquid chromatography-mass spectrometry. Relative to HC participants, grievers had significantly elevated serum AEA but similar 2-AG concentrations. In grievers, serum AEA concentrations were positively associated with depressive and anxiety symptoms, but only in those with low grief symptoms. These novel findings indicate that elevated circulating eCB concentrations are found following bereavement. The eCB signaling response varies based on the degree of grief severity. Circulating eCB measures may have the potential to serve as biomarkers of prolonged grief disorder.


Virologists—Heroes need weapons


Prevalence of and factors associated with mental health problems and suicidality among senior high school students in rural China during the COVID-19 outbreak


title: Imaging manifestations and diagnostic value of chest CT of coronavirus disease 2019 (COVID-19) in the Xiaogan area

text: AIM To report the epidemiological, clinical, and radiological characteristics of patients with COVID-19 in Xiaogan, Hubei, China. MATERIALS AND METHODS The complete clinical and imaging data of 114 confirmed COVID-19 patients treated in Xiaogan Hospital were analysed retrospectively. Data were gathered regarding the presence of chest computed tomography (CT) abnormalities; the distribution, morphology, density, location, and stage of abnormal shadows on chest CT; and observing the correlation between the severity of chest infection and lymphocyte ratio and blood oxygen saturation (SPO2) in patients. RESULTS Chest CT revealed abnormal lung shadows in 110 patients. Regarding lesion distribution, multi-lobe lesions in both lungs were present in most patients (80 cases; 72.7%). Lesions most frequently involved both the peripheral zone and the central zone (62 cases; 56.4%). Regarding lesion morphology, 56 cases (50.1%) demonstrated patchy shadows that were partially fused into large areas. Thirty cases showed ground-glass opacity (27.3%), 30 cases showed the consolidation change (27.3%), and the remaining 50 cases showed both types of changes (45.4%). The progressing stage was the most common stage (54 cases; 49.1%). CT results showed a negative correlation with SPO2 and lymphocyte numbers (p<0.05), with r-values of −0.446 and −0.780, respectively. CONCLUSION Spiral CT is a sensitive examination method, which can be applied to make an early diagnosis and for evaluation of progression, with a diagnostic sensitivity and accuracy better than that of nucleic acid detection.


title: Transnational Quarantine Rhetorics: Public Mobilization in SARS and in H1N1 Flu

text: This essay examines how Chinese governments, local communities, and overseas Chinese in North America responded to the perceived health risks of Severe Acute Respiratory Syndrome (SARS) and H1N1 flu through the use of public and participatory rhetoric about risk and quarantines. Focusing on modes of security and quarantine practices, I examine how globalization and the social crises surrounding SARS and H1N1 flu operated to regulate differently certain bodies and areas. I identify three types of quarantines (mandatory, voluntary, and coerced) and conduct a transnational comparative analysis to investigate the relationships among quarantines, rhetoric, and public communication. I argue that health authorities must openly acknowledge the legitimacy of public input and actively seek public support regarding health crises. Only by collaborating with concerned communities and citizens and by providing careful guidance for public participation can health institutions ensure the efficacy of quarantine orders during emerging epidemics.


title: COVID-19 in der Allgemeinarztpraxis

text: Der Erreger SARS-CoV-2 und die Furcht vor einer Infektion führen in vielen Arztpraxen zu großer Verunsicherung und zu teils chaotischen Zuständen. MMW-Schriftleiter Prof. J. R. Bogner gibt im Folgenden Antworten auf Fragen, die sich viele Hausärzte derzeit stellen.


title: Cell-surface proteolysis, growth factor activation and intercellular communication in the progression of melanoma

text: Abstract Normal skin architecture and melanocyte function is maintained by a dynamic interplay between the melanocytes themselves, the epithelial cells between which they are interspersed, and their microenvironment. The microenvironment consists of the extracellular matrix, fibroblasts, migratory immune cells, and neural elements supported by a vascular network, all within a milieu of cytokines, growth factors, and bioactive peptides as well as proteolytic enzymes. Cells interact with the microenvironment via complex autocrine and paracrine mechanisms. Proteolytic enzymes in melanoma may activate or release growth factors from the microenvironment or act directly on the microenvironment itself, thereby facilitating angiogenesis or tumor cell migration. This review summarizes recent findings regarding the expression, structure and function of proteolytic enzymes at or near the cell surface in cell–cell and cell–stroma interactions during melanoma progression. Cell-surface (membrane) peptidases are a multi-functional group of ectoenzymes that have been implicated in the control of growth and differentiation of many cellular systems. The potential, but yet speculative, role of other membrane-bound molecules, such as multifunctional surface proteins with adhesion and protease activity (ADAM gene family) or the ephrin/Eph receptor protein kinases in the pathogenesis of melanoma are discussed.


title: Human–livestock contacts and their relationship to transmission of zoonotic pathogens, a systematic review of literature

text: BACKGROUND: Micro-organisms transmitted from vertebrate animals – including livestock – to humans account for an estimated 60% of human pathogens. Micro-organisms can be transmitted through inhalation, ingestion, via conjunctiva or physical contact. Close contact with animals is crucial for transmission. The role of intensity and type of contact patterns between livestock and humans for disease transmission is poorly understood. In this systematic review we aimed to summarise current knowledge regarding patterns of human–livestock contacts and their role in micro-organism transmission. METHODS: We included peer-reviewed publications published between 1996 and 2014 in our systematic review if they reported on human–livestock contacts, human cases of livestock-related zoonotic diseases or serological epidemiology of zoonotic diseases in human samples. We extracted any information pertaining the type and intensity of human–livestock contacts and associated zoonoses. RESULTS: 1522 papers were identified, 75 were included: 7 reported on incidental zoonoses after brief animal–human contacts (e.g. farm visits), 10 on environmental exposures and 15 on zoonoses in developing countries where backyard livestock keeping is still customary. 43 studies reported zoonotic risks in different occupations. Occupations at risk included veterinarians, culling personnel, slaughterhouse workers and farmers. For culling personnel, more hours exposed to livestock resulted in more frequent occurrence of transmission. Slaughterhouse workers in contact with live animals were more often positive for zoonotic micro-organisms compared to co-workers only exposed to carcasses. Overall, little information was available about the actual mode of micro-organism transmission. CONCLUSIONS: Little is known about the intensity and type of contact patterns between livestock and humans that result in micro-organism transmission. Studies performed in occupational settings provide some, but limited evidence of exposure response-like relationships for livestock–human contact and micro-organism transmission. Better understanding of contact patterns driving micro-organism transmission from animals to humans is needed to provide options for prevention and thus deserves more attention.


title: The impact of having inadequate safety equipment on mental health

text: BACKGROUND: Concerns are being raised about the impact of inadequate safety equipment on the mental health of healthcare workers during the COVID-19 medical response. AIMS: To assess the impact of inadequate safety equipment on the mental health of service personnel deployed on operations in order to better understand the impact on those working under the similarly demanding conditions of the COVID-19 medical response. METHODS: Self-report surveys were conducted in four operational environments with 3435 personnel providing data. Surveys recorded data on socio-demographic, military and operational characteristics, mental health measures and specific occupational stressors. Analysis through logistic regression explored the association between inadequate equipment and all other factors. RESULTS: A total of 3401 personnel provided data on their perceptions of the adequacy of their equipment, of which 532 (15%) stated that they had a lot of concerns that they did not have the right equipment in working order. Analysis found significantly greater odds of reporting symptoms of common mental health disorders (CMD), 2.49 (2.03–3.06), post-traumatic stress disorder (PTSD), 2.99 (2.11–4.24), poorer global health 2.09 (1.62–2.70) and emotional problems 1.69 (1.38–2.06) when individuals reported working with inadequate equipment. Analyses remained significant when adjusted for confounding factors such as rank, sex and operational environment. CONCLUSIONS: An individual’s perception of having inadequate equipment is significantly associated with symptoms of CMD, probable PTSD, poorer global health and increased reporting of emotional problems. This in turn may impact on their ability to safely carry out their duties and may have longer-term mental health consequences.


title: Cytokine Profiles in Human Immunodeficiency Virus-Infected Children Treated With Highly Active Antiretroviral Therapy

text: CONTEXT: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children. OBJECTIVE: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection. SETTING: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong. PATIENTS: Ten Asian and 2 Eurasian children infected with HIV-1 by mother-to-child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART). MAIN OUTCOME MEASURES: Numbers of unstimulated and mitogen-activated cytokine-secreting cells (IFN-gamma, interleukin [IL]-2, IL-4, IL-6, IL-10, IL-12, and TNF-alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads. RESULTS: Mitogen-stimulated IL-2-secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A-induced IFN-gamma, Con A-induced IL-4, and unstimulated IL-10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN-gamma, IL-2-, IL-4-, and IL-12-secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3-4 years of treatment but declined thereafter. CONCLUSION: Alterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme-linked immunospots (ELISPOTs) could contribute to pediatric patient management.


title: Healthcare utilization among breast cancer patients during the COVID-19 outbreak

text: OBJECTIVE: Continuing to utilize healthcare as needed during an epidemic outbreak is significant, in general, and especially for cancer patients. Therefore, this study aimed to explore factors associated with health services utilization among breast cancer patients during the coronavirus disease (COVID-19) outbreak. METHOD: A cross-sectional online survey was conducted among 151 women with breast cancer. Participants completed measures of perceived health status, perceived susceptibility to COVID-19, anxiety, coping resources, health services utilization (contact with healthcare professionals and cancellation of an appointment to the oncology/hematology clinic), and socio-demographic questionnaires. A multiple hierarchical regression was calculated; contact with healthcare professionals was the dependent variable. In addition, a logistic regression was calculated; cancellation of an appointment to the oncology/hematology clinic because of the COVID-19 was the dependent variable. RESULTS: Breast cancer patients’ contact with healthcare professionals was lower than their contact prior to the pandemic. A higher extent of contact with healthcare professionals was related to patients’ perception of health as bad/reasonable, lower perceived susceptibility, a lower sense of mastery, and higher social support. In addition, the odds of cancelling an appointment to the oncology/hematology clinic were higher in the presence of additional chronic illnesses and a higher sense of mastery. SIGNIFICANCE OF RESULTS: The results could provide public health agencies with a more complete picture of the impact of the COVID-19 epidemic among breast cancer patients. This is significant because, in the event that COVID-19 re-emerges, the findings of the current study could help guide public health officials and possibly prevent the future avoidance of health services’ use among this high-risk population.


title: Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense

text: Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions. Here, we review the mechanisms underlying HDAC regulation during herpesvirus infection. We next discuss the roles of acetylation in host defense against herpesvirus infection. Finally, we provide a perspective on the contribution of current mass spectrometry-based “omic” technologies to infectious disease research, offering a systems biology view of infection.


title: Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody

text: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.


title: Receptor-mediated induction of human dermal fibroblast ectoaminopeptidase N by glucocorticoids

text: Aminopeptidase N was demonstrated in human dermal fibroblasts as an ectoenzyme. The enzyme has wide substrate specificity, with a K (m) of 0.63 mM and V (max) of 338 nmol min(−1) mg(−1). Addition of fetal calf serum to the culture medium increased aminopeptidase N activity up to 63% by 10% serum in a 48-h culture. Treatment of fibroblasts by dexamethasone increased ectoaminopeptidase N activity in a dose- and time-dependent manner. Maximal increase of aminopeptidase N occurred after treatment with 1 μM dexamethasone for 3 days. Actinomycin D, a blocker of RNA synthesis, and cycloheximide, an inhibitor of protein synthesis, did not alter basal aminopeptidase N activity. However, they prevented stimulation by dexamethasone. RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone-induced increase in aminopeptidase N activity. This study shows that human dermal fibroblasts contain ectoaminopeptidase N controlled by glucocorticoids through a receptor-mediated mechanism.


Should I be worried about carrying the virus that causes COVID‐19 home on my clothes?


title: Pharmacological modulation of cough reflex

text: Abstract The cough reflex is an attack of powerful expiratory efforts produced by active contractions of the expiratory muscles, preceded by deep inspirations. Cough is a normal physiological defensive reflex responsible for keeping the airways free of obstruction and harmful substances. However, cough is also the most frequent symptom of acute respiratory system diseases and is the most common reason why sick patients visit physicians. The largest diagnostic group associated with chronic cough is asthma or asthma-like syndromes and chronic obstructive pulmonary disease. Furthermore, gastroesophageal reflux, rhinitis/postnasal drip syndrome and unpleasant side effects accompanying the therapy with angiotensin-converting enzyme inhibitors (ACEI) represent other causes of chronic cough. The cough reflex may be elicited by the activation of receptors of non-myelinated nociceptive Aδ-fibers and C-fibers and receptors of myelinated Aδ-fibers distributed throughout the respiratory tract. In recent times as proper cough receptors are thought to be rapidly adapting receptors (RARs) of myelinated fibers, C-fibers and transient receptor potential vanilloid 1 (TRPV1) localize on the non-myelinated fibers. As the pathological cough (especially its chronic form) has significant impact on patient's quality of life, observed either in physical activity or psychosocial domain, various treatment attitudes are used for different forms of cough (acute, subacute, chronic, productive, nonproductive, psychogenic, asthma-associated, or painful). Interest of research in this field is accompanied with the fact, that many antitussive drugs (mainly from the opioid group), which have been the antitussives of choice for decades, are limited by their unpleasant and very often adverse reactions. In this chapter the authors divided the drugs used in the pharmacological treatment of cough into several groups. These include the drugs acting at the level of receptors, the drugs affecting the propagation of cough impulses in afferent nerves, the drugs modulating the central coordination of cough reflex, the drugs acting at the level of efferent nerves, and the drugs affecting the effectors. Efficacy of many antitussive agents is connected with their influence on more than one level of cough reflex. Another group used in the therapy of cough are mucoactive substances that change the dry, irritant and nonproductive cough into the so-called productive cough with nonirritating expectoration. The last-mentioned group in this chapter is demulcerative and hydrating drugs, which can create a defense layer protecting the mucous membranes from other irritant stimuli.


title: Environmental and infectious conditions in sports

text: The hearts and lungs of athletes are subject to damage from a wide array of infections and environmental factors. Mild to moderate exercise has been shown to be beneficial to overall health, and strenuous exercise simply requires proper rest and rehabilitation to ensure its beneficial effects as well. Simple colds and URTIs are very common in athletes and do not usually require significant intervention. Any suspected cardiac infection mandates a thorough evaluation and proper management to prevent catastrophic consequences. High altitudes can be helpful in enhancing performance, but caution must be exercised at even modest altitude to prevent serious complications. With diving, participants should know their time limits and ascend properly to avoid serious complications. Keeping the heart and lungs in a good state of health is a major priority for the weekend warrior and world-class athletes alike. A thorough knowledge of infections and environmental issues in the cardiopulmonary health of athletes should always be of highest priority.


title: A minute virus of canines (MVC: canine bocavirus) isolated from an elderly dog with severe gastroenteritis, and phylogenetic analysis of MVC strains

text: Abstract Two of the three adult dogs kept in a family developed severe gastroenteritis. From the feces of one of the affected dogs a minute virus of canines (MVC) was detected by PCR and virus isolation. That this virus had recently infected the dogs was indicated by high anti-MVC antibody titers of their sera. No other virus commonly associated with canine gastrointestinal disease was implicated. As no previous association of MVC infection and disease in aged dogs had been described, further characterization of the isolated virus was performed to determine if it had unique pathogenic or genetic properties. Experimental infection of adult dogs did not result in clinical disease and comparison of the viral genome with other MVCs did not reveal any novel elements. The American, Japanese and Korean MVC strains studied were closely related to bocaviruses of bovine and human origin, and appeared to have evolved uniquely in the dog population after dividing from the common ancestor of bocaviruses. Further detailed clinical and virological studies are warranted to define the role of MVCs in disease in adult dogs.


Re-orienting policy for growing food to nourish communities


An integrated national scale SARS-CoV-2 genomic surveillance network


title: Chapter 45 Naked Mole Rat

text: This chapter describes the use of the naked mole rat in the research laboratory setting giving details on its anatomy, natural habitat, reproductive behavior, and physiology followed by a detailed description of its organ systems. This is followed by sections on aging, husbandry of the naked mole rat, colony health, and finally the main models used in research.


title: The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

text: BACKGROUND: Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. METHODS: Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. RESULTS: By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. CONCLUSION: This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.


title: SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus

text: BACKGROUND: 9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood. PRINCIPAL FINDINGS/METHODOLOGY: In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. CONCLUSION/SIGNIFICANCE: Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.


title: COVID-19 findings identified in chest computed tomography: a pictorial essay.

text: The disease caused by the new coronavirus, or COVID-19, has been recently described and became a health issue worldwide. Its diagnosis of certainty is given by polymerase chain reaction. High-resolution computed tomography, however, is useful in the current context of pandemic, especially for the most severe cases, in assessing disease extent, possible differential diagnoses and searching complications. In patients with suspected clinical symptoms and typical imaging findings, in which there is still no laboratory test result, or polymerase chain reaction is not available, the role of this test is still discussed. In addition, it is important to note that part of the patients present false-negative laboratory tests, especially in initial cases, which can delay isolation, favoring the spread of the disease. Thus, knowledge about the COVID-19 and its imaging manifestations is extremely relevant for all physicians involved in the patient care, clinicians or radiologists.


title: The impact of preoperative screening system on head and neck cancer surgery during the COVID-19 pandemic: Recommendations from the nationwide survey in Japan

text: OBJECTIVE: the pandemic of coronavirus disease 2019 (COVID-19), hospitals worldwide are at risk of nosocomial infection. Preoperative identification of COVID-19 in patients who are scheduled to be admitted to the hospital is essential to preventing the collapse of medical facility. In Japan, the preoperative observation and screening tests with the RT-PCR testing for the new coronavirus (SARS-CoV-2) and chest CT scan are recommended for head and neck cancer surgery during the COVID-19 pandemic. METHOD: We conducted surveys of the current situation in Japan through the internet. RESULTS: Chest CT scan was fully performed (90%), but the RT-PCR testing was not adequately performed (51%). CONCLUSION: Although the current screening system can be considered effective to a certain extent, we recommend further widespread use of pre-admission RT-PCR testing not only for patients with head and neck cancer surgery but also for all the hospitalized patients, in order to promote safer treatments, during the COVID-19 pandemic.


title: Clinical features of severe patients infected with 2019 novel coronavirus: a systematic review and meta-analysis

text: Background: 2019 novel coronavirus disease (COVID-19) has posed significant threats to public health To identify and treat the severe and critical patients with COVID-19 is the key clinical problem to be solved The present study aimed to evaluate the clinical characteristics of severe and non-severe patients with COVID-19 Methods: We searched independently studies and retrieved the data that involved the clinical characteristics of severe and non-severe patients with COVID-19 through database searching Two authors independently retrieved the data from the individual studies, assessed the study quality with Newcastle-Ottawa Scale and analyzed publication bias by Begg's test We calculated the odds ratio (OR) of groups using fixed or random-effect models Results: Five studies with 5,328 patients confirmed with COVID-19 met the inclusion criteria Severe patents were older and more common in dyspnea, vomiting or diarrhea, creatinine >104 micromol/L, procalcitonin >/=0 05 ng/mL, lymphocyte count <1 5x10(9)/L and bilateral involvement of chest CT Severe patents had higher risk on complications including acute cardiac injury (OR 13 48;95% CI, 3 60 to 50 47, P<0 001) or acute kidney injury (AKI) (OR 11 55;95% CI, 3 44 to 38 77, P<0 001), acute respiratory distress syndrome (ARDS) (OR 26 12;95% CI, 11 14 to 61 25, P<0 001), shock (OR 53 17;95% CI, 12 54 to 225 4, P<0 001) and in-hospital death (OR 45 24;95% CI, 19 43 to 105 35, P<0 001) Severe group required more main interventions such as received antiviral therapy (OR 1 69;95% CI, 1 23 to 2 32, P=0 001), corticosteroids (OR 5 07;95% CI, 3 69 to 6 98, P<0 001), CRRT (OR 37 95;95% CI, 7 26 to 198 41, P<0 001) and invasive mechanical ventilation (OR 129 35;95% CI, 25 83 to 647 68, P<0 001) Conclusions: Severe patients with COVID-19 had more risk of clinical characteristics and multiple system organ complications Even received more main interventions, severe patients had higher risk of mortality


title: Generality of endemic prevalence formulae

text: Abstract In simple infection models, the susceptible proportion s * in endemic equilibrium is related to the basic reproduction number R 0 by s * = 1 / R 0 . We investigate the extent to which this relationship remains valid under more realistic modelling assumptions. In particular, we relax the biologically implausible assumptions that individuals’ lifetimes and infectious periods follow exponential distributions; allow a general recruitment process; allow for multiple stages of infection; and consider extension to a multigroup model in which the groups may represent, for instance, spatial heterogeneity, or the existence of super-spreaders. For a homogeneous population, we find that: (i) the susceptible proportion is s * = 1 / R 0 e , where R 0 e is a modified reproduction number, equal to R 0 only in certain circumstances; (ii) the proportions of the population in each stage of infection are proportional to the expected time spent by an infected individual in that stage before recovery or death. We demonstrate robustness of the formula s * = 1 / R 0 for many human infections by noting conditions under which R 0 e is approximately equal to R 0, while pointing out other circumstances under which this approximation fails. For heterogeneous populations, the formula s * = 1 / R 0 does not hold in general, but we are able to exhibit symmetry conditions under which it is valid.


title: Evaluation of simple nucleic acid extraction methods for the detection of SARS-CoV-2 in nasopharyngeal and saliva specimens during global shortage of extraction kits

text: BACKGROUND: The severe shortage of nucleic acid extraction kits during the current COVID-19 pandemic represents a key limiting factor in testing capacity. OBJECTIVES: This study compared the results of SARS-CoV-2 RT-PCR using different simple nucleic acid extraction methods on nasopharyngeal and saliva specimens. STUDY DESIGN: Fifty nasopharyngeal swab and saliva specimens previously tested positive for SARS-CoV-2 were retrieved. Three different methods of nucleic acid extraction were compared. The first method involves incubating the specimen, with proteinase K, and then heat treatment at 98°C for 5 min (PHK); the second method involves heat treatment at 98°C fir 5 min without proteinase K pre-incubation (heat only); the third method involves no pre-processing steps (direct). The products from all 3 methods were tested by SARS-CoV-2 RT-PCR. RESULTS: PKH had significantly higher positive rate in SARS-CoV-2 RT-PCR (80%)than those of heat only (58%; P=0.001) or direct (56%; P=0.002). The median Ct value was significantly earlier for PKH (median Ct: 37.0, IQR 31.7-40) than that of heat only (median Ct: 40, IQR 36.2-41; P<0.0001) and direct (median Ct, 37.5; IQR 33.9-41.0; P=0.0049). Subgroup analysis showed that PKH had higher detection rate, lower limit of detection and earlier Ct values than the other two groups for both NPS and saliva specimens. CONCLUSIONS: PKH pre-processing resulted in the highest detection rate of SARS-CoV-2 by RT-PCR, and can serve as an alternative for nucleic acid extraction when commercial extraction kits are not available.


title: Virulence Potential of Fusogenic Orthoreoviruses

text: Several severe respiratory virus infections that have emerged during the past decade originated in animals, including bats. In Indonesia, exposure to bats has been associated with increased risk of acquiring orthoreovirus infection. Although orthoreovirus infections are mild and self-limiting, we explored their potential for evolution into a more virulent form. We used conventional virus culture, electron microscopy, and molecular sequencing to isolate and identify orthoreoviruses from 3 patients in whom respiratory tract infection developed after travel to Indonesia. Virus characterization by plaque-reduction neutralization testing showed antigenic similarity, but sequencing of the small segment genes suggested virus reassortment, which could lead to increased virulence. Bats as a reservoir might contribute to virus evolution and genetic diversity, giving orthoreoviruses the potential to become more virulent. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.


title: Chimeric Antigen Receptor T Cell Therapy During the COVID-19 Pandemic

text: ABSTRACT The SARS-CoV-2 coronavirus (COVID-19) pandemic has significantly impacted the delivery of cellular therapeutics, including chimeric antigen receptor (CAR) T cells. This impact has extended beyond patient care to include logistics, administration, and distribution of increasingly limited health care resources. Based on the collective experience of the CAR T-cell Consortium investigators, we review and address several questions and concerns regarding cellular therapy administration in the setting of COVID-19 and make general recommendations to address these issues. Specifically, we address (1) necessary resources for safe administration of cell therapies; (2) determinants of cell therapy utilization; (3) selection among patients with B cell non-Hodgkin lymphomas and B cell acute lymphoblastic leukemia; (4) supportive measures during cell therapy administration; (5) use and prioritization of tocilizumab; and (6) collaborative care with referring physicians. These recommendations were carefully formulated with the understanding that resource allocation is of the utmost importance, and that the decision to proceed with CAR T cell therapy will require extensive discussion of potential risks and benefits. Although these recommendations are fluid, at this time it is our opinion that the COVID-19 pandemic should not serve as reason to defer CAR T cell therapy for patients truly in need of a potentially curative therapy.


title: Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations

text: The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.


Screening of donor and recipient prior to solid organ transplantation


Response to “Another vision from the coronavirus health crisis in Spain: the perspective from 'Plena inclusión' Developmental Disabilities associative movement.” By M. Galvan.


title: [The importance of strengthening the ability of fundamental disease prevention and control system from the perspective of the epidemic situation of COVID-19].

text: COVID-19 has been in epidemic for nearly two months. The prevention and control measures have achieved remarkable results. From the response and disposal process of this epidemic, it is exposed that fundamental disease prevention and control system are insufficient in human resources and ability of laboratory testing. It is suggested that the disease control institutions should strengthen the construction of these aspects in future.


title: Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of Glycyrrhiza glabra L. (Fabaceae)

text: Traditional herbal remedies have been attracting attention as prospective alternative resources of therapy for diverse diseases across many nations. In recent decades, medicinal plants have been gaining wider acceptance due to the perception that these plants, as natural products, have fewer side effects and improved efficacy compared to their synthetic counterparts. Glycyrrhiza glabra L. (Licorice) is a small perennial herb that has been traditionally used to treat many diseases, such as respiratory disorders, hyperdipsia, epilepsy, fever, sexual debility, paralysis, stomach ulcers, rheumatism, skin diseases, hemorrhagic diseases, and jaundice. Moreover, chemical analysis of the G. glabra extracts revealed the presence of several organic acids, liquirtin, rhamnoliquirilin, liquiritigenin, prenyllicoflavone A, glucoliquiritin apioside, 1-metho-xyphaseolin, shinpterocarpin, shinflavanone, licopyranocoumarin, glisoflavone, licoarylcoumarin, glycyrrhizin, isoangustone A, semilicoisoflavone B, licoriphenone, and 1-methoxyficifolinol, kanzonol R and several volatile components. Pharmacological activities of G. glabra have been evaluated against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium falciparum, and completely eradicated P. yoelii parasites. Additionally, it shows antioxidant, antifungal, anticarcinogenic, anti-inflammatory, and cytotoxic activities. The current review examined the phytochemical composition, pharmacological activities, pharmacokinetics, and toxic activities of G. glabra extracts as well as its phytoconstituents.


title: DNA vaccines and their applications in veterinary practice: current perspectives

text: Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. The potential of DNA vaccines to act in presence of maternal antibodies, its stability and cost effectiveness and the non-requirement of cold chain have heightened the prospects. Even though great strides have been made in nucleic acid vaccination, still there are many areas that need further research for its wholesome practical implementation. Major areas of concern are vaccine delivery, designing of suitable vectors and cytotoxic T cell responses. Also, the induction of immune responses by DNA vaccines is inconclusive due to the lack of knowledge regarding the concentration of the protein expressed in vivo. Alternative delivery systems having higher transfection efficiency and the use of cytokines, as immunomodulators, needs to be further explored. Recently, efforts are being made to modulate and prolong the active life of dendritic cells, in order to make antigen presentation a more efficacious one. For combating diseases like acquired immunodeficiency syndrome (AIDS), influenza, malaria and tuberculosis in humans; and foot and mouth disease, Aujesky’s disease, swine fever, rabies, canine distemper and brucellosis in animals, DNA vaccine clinical trials are underway. This review highlights the salient features of DNA vaccines, and measures to enhance their efficacy so as to devise an effective and novel vaccination strategy against animal diseases.


title: Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes

text: In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs. Communicated by Ramaswamy H. Sarma


title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland

text: The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland.


title: Production of Recombinant N Protein of Infectious Bronchitis Virus Using the Baculovirus Expression System and Its Assessment as a Diagnostic Antigen

text: The avian coronavirus-infectious bronchitis virus (AvCoV-IBV) is recognized as an important avian pathogen, and new viral variants are a continuous threat to the poultry industry worldwide. Sensitive diagnostics and efficacious vaccines are necessary to combat IBV infections in chickens. The aim of this study was to produce recombinant N protein of IBV in the baculovirus system to use in ELISA diagnostic tests in order to enable the assessment of the sero-prevalence and risk of IBV infections in chickens in Turkey. For this, the gene encoding the N protein of the Beaudette strain of IBV was expressed using a recombinant baculovirus expression system. The recombinant N protein was purified using Ni-NTA affinity chromatography. An estimated 50-kDa recombinant protein corresponding to the expected molecular weight of IBV N including the 6xHis tag was detected using an anti-His monoclonal antibody. Specific immunoreactivity of the recombinant protein was confirmed by Western blot using antiserum obtained from vaccinated and naturally infected chicken from Turkey as well as using a monoclonal antibody raised against the N protein of the IBV Massachusetts strain. The results obtained with the in-house ELISA had high agreement with a commercial ELISA. Immunoreactivity analysis using antisera in Western blotting and the in-house ELISA suggests that the recombinant IBV N protein could be broadly cross-reactive with antisera produced against different IBV strains. We conclude that the recombinant baculovirus expressed IBV N protein could serve as a useful diagnostic antigen for detection of IBV infections in chickens by ELISA.


title: Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations

text: Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.


MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS – MERS, MERS CoV


Histopathology of viral infections of the lung


title: Systematic Review of Economic Evaluations of Preparedness Strategies and Interventions against Influenza Pandemics

text: BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies.


title: Complete Genome Sequence of a Severe Acute Respiratory Syndrome-Related Coronavirus from Kenyan Bats

text: We identified a strain of betacoronavirus BtKY72/Rhinolophus sp./Kenya/2007 (here BtKY72) from rectal swab samples in Kenyan bats. This paper reports the complete genomic sequence of BtKY72, which is closely related to BtCoV/BM48-31/Bulgaria/2008, a severe acute respiratory syndrome (SARS)-related virus from Rhinolophus bats in Europe.


title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins

text: Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.


title: A Nationwide Survey of Psychological Distress among Italian People during the COVID-19 Pandemic: Immediate Psychological Responses and Associated Factors

text: The uncontrolled spread of the coronavirus disease 2019 (COVID-19) has called for unprecedented measures, to the extent that the Italian government has imposed a quarantine on the entire country. Quarantine has a huge impact and can cause considerable psychological strain. The present study aims to establish the prevalence of psychiatric symptoms and identify risk and protective factors for psychological distress in the general population. An online survey was administered from 18–22 March 2020 to 2766 participants. Multivariate ordinal logistic regression models were constructed to examine the associations between sociodemographic variables; personality traits; depression, anxiety, and stress. Female gender, negative affect, and detachment were associated with higher levels of depression, anxiety, and stress. Having an acquaintance infected was associated with increased levels of both depression and stress, whereas a history of stressful situations and medical problems was associated with higher levels of depression and anxiety. Finally, those with a family member infected and young person who had to work outside their domicile presented higher levels of anxiety and stress, respectively. This epidemiological picture is an important benchmark for identifying persons at greater risk of suffering from psychological distress and the results are useful for tailoring psychological interventions targeting the post-traumatic nature of the distress.


title: Porcine Deltacoronavirus Accessory Protein NS7a Antagonizes IFN-β Production by Competing With TRAF3 and IRF3 for Binding to IKKε

text: As an emerging swine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) not only causes serious diarrhea in suckling piglets but also possesses the potential for cross-species transmission, which has sparked growing interest when studying this emerging virus. We previously identified a novel accessory protein NS7a encoded by PDCoV; however, the function of NS7a was not resolved. In this study, we demonstrated that PDCoV NS7a is an interferon antagonist. Overexpression of NS7a notably inhibited Sendai virus (SeV)-induced interferon-β (IFN-β) production and the activation of IRF3 rather than NF-κB. NS7a also inhibited IFN-β promoter activity induced by RIG-I, MDA5, MAVS, TBK1, and IKKε, which are key components of the RIG-I-like receptor (RLR) signaling pathway but not IRF3, the transcription factor downstream of TBK1/IKKε. Surprisingly, NS7a specifically interacts with IKKε but not with the closely related TBK1. Furthermore, NS7a interacts simultaneously with the kinase domain (KD) and the scaffold dimerization domain (SDD) of IKKε, competing with TRAF3, and IRF3 for binding to IKKε, leading to the reduction of RLR-mediated IFN-β production. The interactions of TRAF3-IKKε and IKKε-IRF3 are also attenuated in PDCoV-infected cells. Taken together, our results demonstrate that PDCoV NS7a inhibits IFN-β production by disrupting the association of IKKε with both TRAF3 and IRF3, revealing a new mechanism utilized by a PDCoV accessory protein to evade the host antiviral innate immune response.


title: Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives

text: The advancements in technology and manufacturing processes have allowed the development of new derivatives, biosimilar or advanced improved versions for approved antibodies each year for treatment regimen. There are more than 700 antibody-based molecules that are in different stages of phase I/II/ III clinical trials targeting new unique targets. To date, approximately more than 80 monoclonal antibodies (mAbs) have been approved. A total of 7 novel antibody therapeutics had been granted the first approval either in the United States or European Union in the year 2019, representing approximately 20% of the total number of approved drugs. Most of these licenced mAbs or their derivatives are either of hybridoma origin or their improvised engineered versions. Even with the recent development of high throughput mAb generation technologies, hybridoma is the most favoured method due to its indigenous nature to preserve natural cognate antibody pairing information and preserves innate functions of immune cells. The recent advent of antibody engineering technology has superseded the species level barriers and has shown success in isolation of hybridoma across phylogenetically distinct species. This has led to the isolation of monoclonal antibodies against human targets that are conserved and non-immunogenic in the rodent. In this review, we have discussed in detail about hybridoma technology, its expansion towards different animal species, the importance of antibodies isolated from different animal sources that are useful in biological applications, advantages, and limitations. This review also summarizes the challenges and recent progress associated with hybridoma development, and how it has been overcome in these years to provide new insights for the isolation of mAbs.


title: Characterization of humoral responses in mice immunized with plasmid DNAs encoding SARS-CoV spike gene fragments

text: Abstract The immunological characteristics of SARS-CoV spike protein were investigated by administering mice with plasmids encoding various S gene fragments. We showed that the secreting forms of S1, S2 subunits and the N-terminus of S1 subunit (residues 18–495) were capable of eliciting SARS-CoV specific antibodies and the region immediate to N-terminus of matured S1 protein contained an important immunogenic determinant for elicitation of SARS-CoV specific antibodies. In addition, mice immunized with plasmids encoding S1 fragment developed a Th1-mediated antibody isotype switching. Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. These results provide insights into understanding the immunological characteristics of spike protein and the development of subunit vaccines against SARS-CoV.


title: Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

text: Abstract Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatments for COPD are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD. Since comorbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its comorbidities. It is now emerging that up to 50% of COPD patients have metabolic syndrome (MetS) as a comorbidity. It is currently not clear whether metabolic syndrome is an independent co-existing condition or a direct consequence of the progressive lung pathology in COPD patients. As MetS has important clinical implications on COPD outcomes, identification of disease mechanisms linking COPD to MetS is the key to effective therapy. In this comprehensive review, we discuss the potential mechanisms linking MetS to COPD and hence plausible therapeutic strategies to treat this debilitating comorbidity of COPD.


title: Reverse transcriptase-polymerase chain reaction for the detection equine rhinitis B viruses and cell culture isolation of the virus

text: Equine rhinitis B virus (ERBV), genus Erbovirus, family Picornaviridae occurs as two serotypes, ERBV1 and ERBV2. An ERBV-specific nested reverse transcriptase-polymerase chain reaction (RT-PCR) that amplified a product within the 3D(pol) and 3′ non-translated region of the viral genome was developed. The RT-PCR detected all 24 available ERBV1 isolates and one available ERBV2 isolate. The limit of detection for the prototype strain ERBV1.1436/71 was 0.1 50% tissue culture infectious doses. The RT-PCR was used to detect viral RNA in six of 17 nasopharyngeal swab samples from horses that had clinical signs of acute febrile respiratory disease but from which ERBV was not initially isolated in cell culture. The sequences of these six ERBV RT-PCR positive samples had 93–96% nucleotide identity with six other partially sequenced ERBV1 isolates and one ERBV2. ERBV was isolated from one of the six samples at fourth cell culture passage when it was shown that the addition of 20 mg/mL MgCl(2) to the cell culture medium enhanced the growth of the virus. This isolated virus was antigenically similar to ERBV2.313/75. Determination of the nucleotide sequence of the P1 region of the genome also indicated that the isolate was ERBV2, and it was therefore designated ERBV2.1576/99. This is the first reported isolation of ERBV in Australia. The study highlights the utility of PCR for the identification of viruses in clinical samples that may initially be considered negative by conventional cell culture isolation.


title: Influence of the pandemic dissemination of COVID-19 on radiotherapy practice: A flash survey in Germany, Austria and Switzerland

text: BACKGROUND: The COVID-19 pandemic has already changed our globalised world and its long-term impact is not yet known. It is apparent that businesses and institutions are increasingly affected. COVID-19 discussions often focus on intensive care units in hospitals. However, COVID-19 also effects life-saving and -prolonging radiotherapy for patients suffering from cancer. METHOD: We have conducted a structured online survey among medical physicists in Germany, Austria and Switzerland from March 23rd to 26th 2020. In total 154 responses (82 completed, 72 partially completed) were analysed in the context of the COVID-19 dissemination. RESULTS: 72.4% of the respondent’s state that their processes are affected due to COVID-19, while the top three answers are longer processing times (54.2%), patient no-shows (42.5%) and staff reduction (36.7%). 75.8% expect further unavailability of their personnel in the upcoming weeks. All participants have already taken several measures, especially providing information for patients at the entrance (89.6%) or over the phone (73.6%), restricting access for accompanying persons (77.4%) and providing disinfectant at the entrance (72.6%). DISCUSSION: The results presented in this article aim to support business continuity and risk management for radiotherapy centres to prepare for future challenges. The results show that most radiotherapy centres has implemented initial contingency measures, applying them pragmatically. The main problem however remains, that is the high risk of infection both for patients and medical personnel along with the associated risk of temporarily loss of personnel and ordered closure of business.


title: Structure analysis of the receptor binding of 2019-nCoV

text: Abstract 2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.


title: Coronavirus disease 2019 and gender-related mortality in European countries: A meta-analysis

text: OBJECTIVE: To examine mortality rates related to coronavirus disease 2019 (COVID-19) by gender among European countries. METHODS: PubMed, preprint medRxiv and bioRxiv repositories, and Google were searched for the terms COVID-19, mortality rates, gender, and Europe. Only Google provided a website with appropriate information. COVID-19 cases and deaths from European countries were extracted by gender from the Global Health 50/50 repository up to May 23, 2020. Extracted data included country, the total number of COVID-19 cases and the number of related deaths by gender. Random effects models with the inverse variance method were used for meta-analyses. Results are reported as death risk ratios (RRs). RESULTS: We identified information from 23 European countries that reported separately by gender mortality rates related to COVID-19. The sample comprised 484,919 men and 605,229 women positive for COVID-19. The mortality rate was significantly higher in men than in women (risk ratio = 1.60, 95% confidence interval [CI] 1.53, 1.68). The trend was similar when countries reporting < 5,000, or < 10,000 cases were excluded from the analysis (RR = 1.60, 95% CI 1.52, 1.69 and RR = 1.68; CI 1.62, 1.76, respectively). CONCLUSION: In Europe, the new zoonotic coronavirus causes significantly more deaths in men than in women.


title: Can we predict the occurrence of COVID-19 cases? Considerations using a simple model of growth

text: Abstract This study aimed to present a simple model to follow the evolution of the COVID-19 (CV-19) pandemic in different countries. The cumulative distribution function (CDF) and its first derivative were employed for this task. The simulations showed that it is almost impossible to predict based on the initial CV-19 cases (1st 2nd or 3rd weeks) how the pandemic will evolve. However, the results presented here revealed that this approach can be used as an alternative for the exponential growth model, traditionally employed as a prediction model, and serve as a valuable tool for investigating how protective measures are changing the evolution of the pandemic.


title: Les virus des bronchiolites aiguës

text: Résumé En Normandie, le virus respiratoire syncytial (hRSV) est trouvé dans 64,1 % des cas de bronchiolites aiguës chez l’enfant hospitalisé, les rhinovirus dans 26,8 %, le métapneumovirus humain (hMPV) dans 7,6 % et les virus para-influenza (PIV) dans 3,4 %. Dans les bronchiolites aiguës communautaires, on a une répartition différente : hRSV : 42 %, rhinovirus : 19,5 %, coronavirus : 8 %, PIV : 3,5 %, hMPV : 2,5 %. Le hRSV infecte les nourrissons (86,9 %), dont 53,7 % ont moins de 6 mois et 48,2 % des hRSV sont détectés en novembre et décembre, et 44,5 % en janvier et février. L’épidémie débute la 1re ou 2e semaine d’octobre, mais elle varie d’une année à l’autre et d’une région à l’autre. À l’hôpital, les bronchiolites à hRSV sont passées de 261 cas par épidémies de 1999 à 2003, à 341 cas de 2004 à 2009. Les rhinovirus sont associés à des bronchiolites aiguës dans 38,4 % des cas ; 54,6 % des souches étant identifiées en septembre et octobre, et 38,5 % en mars et avril ; 34,2 % infectent des nourrissons de moins de 6 mois, 37,8 % entre 6 mois et 2 ans, et 19,5 % des enfants entre 2 et 5 ans. Les épidémies à hMPV coïncident avec celles du hRSV mais ont 6 fois moins de cas hospitalisés. Le hMPV infecte les nourrissons (74 %) mais plus âgés que ceux infectés par le hRSV. Il entraîne une bronchiolite aiguë dans 59 % des cas, une pneumonie dans 17 %. Les infections à PIV (environ 100 cas hospitalisés par an) se répartissent en PIV3 : 62,7 %, PIV1 : 25,3 % et PIV2 : 7,3 %. Les PIV1 apparaissent tous les 2 ans, à l’automne. Les infections à PIV3 sont automnales et hivernales, avec des infections au printemps les années sans PIV1. Il y a des bronchiolites aiguës dans 29,8 % des infections à PIV3 et 18,3 % à PIV1. Summary In Normandy (France), human respiratory syncytial virus (hRSV) was detected in 64.1% of acute bronchiolitis in hospitalized children, rhinovirus in 26.8%, human metapneumovirus (hMPV) in 7.6%, and parainfluenza virus (PIV) in 3.4%. The viruses causing acute bronchiolitis in the community were hRSV (42%), rhinovirus (19.5%), coronavirus (8%), PIV (3.5%), and hMPV (2.5%). In 53.7% of the cases, hRSV infected infants (86.9%), 53.7% being less than 6months of age. Of the hRSV cases, 48.2% were detected in November and December and 44.5% in January and February. The hRSV epidemic started the 1st or 2nd week of October but it varied from one year to another and from one region to another. hRSV acute bronchiolitis increased from 261 cases in epidemics from 1999–2003 to 341 cases from 2004–2009. Rhinoviruses gave acute bronchiolitis in 38.4% of cases. A rate of 54.6% of viruses was detected in September and October and 38.5% in March and April. A total of 34.2% of infected infants were under 6months of age, 37.8% between 6months and 2years, and 19.5% were between 2 and 5years old. hMPV epidemics coincided with hRSV epidemics, but they accounted for one-sixth the number of cases. HMPV infected infants (74%) who were older than those infected with hRSV, and the diagnosis was bronchiolitis (59%) and pneumonia (17%). PIV infections (about 100 cases per year) included PIV3 (62.7%), PIV1 (25.3%), and PIV2 (7.3%). PIV1 infections occurred every 2years in the fall. PIV3 infections were observed every year during the fall and winter, with peaks of infections in the spring in the years without PIV1. There were acute cases of bronchiolitis in 29.8% of PIV3 infections and 18.3% in PIV1 infections.


title: Decrease of CD56(+)T cells and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma

text: CD56(+)T cells and CD56(+)natural killer (NK) cells are abundant in the human liver. The aim of this study was the further characterization of these cells in the liver with or without hepatitis C virus (HCV) infection. Liver mononuclear cells (MNC) were isolated from liver specimens obtained from the patients during abdominal surgery. In addition to a flow cytometric analysis, liver MNC and PBMC were cultured with the immobilized anti‐CD3 Ab, IL‐2, or a combination of IL‐2 and IL‐12 and their IFN‐γ production and the antitumor cytotoxicity were assessed. The liver MNC of HCV (−) patients contained 20% CD56(+)T cells whereas the same proportions decreased to 11% in chronic hepatitis livers and to 5% in cirrhotic livers. The proportion of NK cells also decreased in the cirrhotic livers. On the other hand, the populations of these cells in PBMC did not significantly differ among patient groups. The IFN‐γ production and the cytotoxicity against K562 cells, Raji cells, and a hepatocellular carcinoma, HuH‐7 cells, greatly decreased in the cirrhotic liver MNC. In contrast, the cytotoxicity in PBMC did not significantly differ among the patient groups and was lower than that in the liver MNC of HCV (−) patients. CD56(+)T cells and NK cells but not regular T cells purified from liver MNC cultured with cytokines showed potent cytotoxicities against HuH‐7 cells. These results suggest that a decreased number of CD56(+)T cells and NK cells in cirrhotic livers may be related to their susceptibility to hepatocellular carcinoma.


title: Let us unite against COVID-19 – a New Zealand perspective

text: Novel coronavirus 2019 (COVID-19) has shaken the existence of mankind worldwide, including that of New Zealand. In comparison to other countries, New Zealand has had a very low number of confirmed and probable cases as well as COVID-19-related deaths. New Zealand closed its borders and rapidly declared a stringent lockdown to eliminate COVID-19. The country’s ‘go hard, go early’ policy serves as an exemplar for the rest of the world to date. The mysterious nature of COVID-19 has caused tremendous stress and uncertainty leading to universal conflict between public health and state economy. Mental health services and non-government organisations have been proactive in the fight against COVID-19. Though there has been no significant rise in referrals to secondary mental health services to date (4 May 2020), a rapid surge in mental health presentations is widely anticipated. Telehealth may prove to be an efficient and cost-effective tool for the provision of future health services.


title: Equine sarcoid: In situ demonstration of matrix metalloproteinase expression

text: Abstract Sarcoids are the most prevalent equine skin tumours and remain a therapeutic challenge due to their differing clinical morphology, local aggressive behaviour, and high recurrence following surgical treatment. In vitro, sarcoid derived fibroblasts are invasive and express matrix metalloproteinase (MMP) -1, -2 and -9. It was hypothesised that the MMPs produced by neoplastic cells play a role in both their local invasiveness and interaction with the overlying epidermis (picket fence formation). The objective of this morphological study was to investigate the local behaviour and in situ MMP expression pattern in sarcoids of different clinical types. A total of 43 surgically excised sarcoids were examined by histology, immunohistology for the expression of MMP-1, -2 and -9, and transmission electron microscopy. Regardless of the clinical type, sarcoids showed local invasion of the dermis and damage to the basement membrane in areas of interaction with the epidermis. This was associated with MMP-1 expression in both neoplastic cells and epidermis. The results suggest a link between MMP-1 expression and the local aggressiveness of sarcoids regardless of the clinical type.


title: [Novel coronavirus pneumonia related liver injury: etiological analysis and treatment strategy].

text: The outbreak of novel coronavirus pneumonia(NCP) caused by 2019 novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.


title: A Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

text: COVID-19 has become a major global public health burden, currently causing a rapidly growing number of infections and significant morbidity and mortality around the world. Early detection with fast and sensitive assays and timely intervention are crucial for interrupting the spread of the COVID-19 virus (SARS-CoV-2). Using a mismatch-tolerant amplification technique, we developed a simple, rapid, sensitive and visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for SARS-CoV-2 detection based on its N gene. The assay has a high specificity and sensitivity, and robust reproducibility, and its results can be monitored using a real-time PCR machine or visualized via colorimetric change from red to yellow. The limit of detection (LOD) of the assay is 118.6 copies of SARS-CoV-2 RNA per 25 μL reaction. The reaction can be completed within 30 min for real-time fluorescence monitoring, or 40 min for visual detection when the template input is more than 200 copies per 25 μL reaction. To evaluate the viability of the assay, a comparison between the RT-LAMP and a commercial RT-qPCR assay was made using 56 clinical samples. The SARS-CoV-2 RT-LAMP assay showed perfect agreement in detection with the RT-qPCR assay. The newly-developed SARS-CoV-2 RT-LAMP assay is a simple and rapid method for COVID-19 surveillance.


title: Virus discovery: one step beyond

text: Recent advances in the metagenomics field have had huge effects on the identification and characterization of newly emerging viral pathogens. To allow timely and efficient responses to future viral threats, an integrated multidisciplinary approach utilizing expertises in several areas, including clinical assessment, virus surveillance, virus discovery, pathogenesis, and the molecular basis of the host response to infection, is required. It requires the scientific community involved in virus discovery to go one step beyond.


title: Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals

text: The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.


title: The role of the IKK complex in viral infections

text: The NF-κB signal transduction pathway is a critical regulator of multiple cellular functions that ultimately shift the balance between cell survival and death. The cascade is activated by many intrinsic and extrinsic stimuli, which is transduced via adaptor proteins to phosphorylate the IκB kinase (IKK) complex, which in turn phosphorylates the inhibitory IκBα protein to undergo proteasomal degradation and sets in motion nuclear events in response to the initial stimulus. Viruses are important modulators of the NF-κB cascade and have evolved multiple mechanisms to activate or inhibit this pathway in a manner conducive to viral multiplication and establishment of a productive infectious cycle. This is a subject of extensive research by multiple laboratories whereby unraveling the interactions between specific viral components and members of the NF-κB signal transduction cascade can shed unique perspectives on infection associated pathogenesis and novel therapeutic targets. In this review, we highlight the interactions between components of the IKK complex and multiple RNA and DNA viruses with the emphasis on mechanisms by which the interaction feeds the infection. Understanding these interactions will shed light on the exploitative capabilities of viruses to maintain an environment favorable for a productive infection.


title: Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells

text: Infectious diseases caused by human immunodeficiency virus (HIV) and other highly pathogenic enveloped viruses, have threatened the global public health. Most antiviral drugs act as passive defenders to inhibit viral replication inside the cell, while a few of them function as gate keepers to combat viruses outside the cell, including fusion inhibitors, e.g., enfuvirtide, and receptor antagonists, e.g., maraviroc, as well as virus inactivators (including attachment inhibitors). Different from fusion inhibitors and receptor antagonists that must act in the presence of target cells, virus inactivators can actively inactivate cell-free virions in the blood, through interaction with one or more sites in the envelope glycoproteins (Envs) on virions. Notably, a number of protein- and peptide-based virus inactivators (PPVIs) under development are expected to have a better utilization rate than the current antiviral drugs and be safer for in vivo human application than the chemical-based virus inactivators. Here we have highlighted recent progress in developing PPVIs against several important enveloped viruses, including HIV, influenza virus, Zika virus (ZIKV), dengue virus (DENV), and herpes simplex virus (HSV), and the potential use of PPVIs for urgent treatment of infection by newly emerging or re-emerging viruses.


title: Rhinitis, Asthma and Respiratory Infections among Adults in Relation to the Home Environment in Multi-Family Buildings in Sweden

text: Risk factors for rhinitis, asthma and respiratory infections in the home environment were studied by a questionnaire survey. Totally 5775 occupants (≥18 years old) from a stratified random sample of multi-family buildings in Sweden participated (46%). 51.0% had rhinitis in the last 3 months (current rhinitis); 11.5% doctor diagnosed asthma; 46.4% respiratory infections in the last 3 months and 11.9% antibiotic medication for respiratory infections in the last 12 months. Associations between home environment and health were analyzed by multiple logistic regression, controlling for gender, age and smoking and mutual adjustment. Buildings constructed during 1960–1975 were risk factors for day time breathlessness (OR = 1.53, 95%CI 1.03–2.29). And those constructed during 1976–1985 had more current rhinitis (OR = 1.43, 95%CI 1.12–1.84) and respiratory infections (OR = 1.46, 95%CI 1.21–1.78). Cities with higher population density had more current rhinitis (p = 0.008) and respiratory infections (p<0.001). Rented apartments had more current rhinitis (OR = 1.23, 95%CI 1.07–1.40), wheeze (OR = 1.20, 95%CI 1.02–1.41), day time breathlessness (OR = 1.31, 95%CI 1.04–1.66) and respiratory infections (OR = 1.13, 95%CI 1.01–1.26). Living in colder parts of the country was a risk factor for wheeze (p = 0.03) and night time breathlessness (p = 0.002). Building dampness was a risk factor for wheeze (OR = 1.42, 95%CI 1.08–1.86) and day time breathlessness (OR = 1.57, 95%CI 1.09–2.27). Building dampness was a risk factor for health among those below 66 years old. Odor at home was a risk factor for doctor diagnosed asthma (OR = 1.49, 95%CI 1.08–2.06) and current asthma (OR = 1.52, 95%CI 1.03–2.24). Environmental tobacco smoke (ETS) was a risk factor for current asthma (OR = 1.53, 95%CI 1.09–2.16). Window pane condensation was a risk factor for antibiotic medication for respiratory infections (OR = 1.41, 95%CI 1.10–1.82). In conclusion, rhinitis, asthma and respiratory infections were related to a number of factors in the home environment. Certain building years (1961–1985), building dampness, window pane condensation and odor in the dwelling may be risk factors.


title: Organisation d’un détachement pour renfort médical en situation de crise sanitaire lors de la pandémie COVID-19: retour sur une collaboration entre les CHU de Lille et de Strasbourg

text: Résumé La pandémie de COVID-19 a mis sous tension extrême un système de santé fondé essentiellement sur une organisation locale et régionale. Au plus fort de la crise, la nécessité exceptionnelle de faire appel à un renfort de médecins spécialistes en anesthésie-réanimation disponibles sur le territoire français a permis d’optimiser la prise en charge des patients les plus gravement atteints par le SARS-CoV-2 hospitalisés au CHU de Strasbourg. Cette formidable chaîne de solidarité a fonctionné grâce à une co-organisation administrative et médicale. Une gestion rigoureuse des moyens nécessaires doit permettre l’anticipation des besoins en renfort, la préparation de leurs arrivées et leurs affections dans un service adapté à leurs compétences. Afin d’optimiser l’efficience d’un tel processus, le maximum doit être fait pour faciliter l’exercice du praticien en renfort. Le facteur humain, souvent négligé dans nos exercices médicaux, se révèle être une fois de plus une composante essentielle dans la gestion de crise. Abstract The COVID-19 pandemic put the French health system, mainly based on local and regional organisation, under tremendously high pressure. During the crisis climax, many hospitals, like the Strasbourg University Hospital, had to rely on backup from available anaesthesiologists, working in spared regions, to relieve healthcare resources and reinforce local teams. This remarkable chain of solidarity compensated for limited healthcare resources and allowed for appropriate, high-level care of severe COVID-19 patients in Strasbourg. Adequate allocation of medical resources required anticipation, reactivity and a skill-oriented dispatch from both administrative and medical perspectives. To maximise its efficacy, this system should focus on facilitating rapid integration of medical resources from abroad in ancillary tasks and ease their rapid acquisition of local protocols. One again, human factor turned out to be the most decisive element in mitigating the COVID-19 pandemic.


title: Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules

text: Abstract Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in Vero E6 and Huh7 cells on two different CCHFV strains. Several combinations, including ribavirin, were assayed to test a potential synergistic effect. The two molecules inhibited CCHFV, and depending on the virus and the cell lines, the 50% inhibitory concentration (IC50) values for chloroquine and chlorpromazine ranged from 28 to 43 and 10.8–15.7μM, respectively. Time-of-addition studies demonstrated that these molecules had a direct effect on CCHFV infectivity and spread. The antiviral activity of the two molecules was still effective even when added up to 6h post-infection and up to 24h. The selectivity index ranging from 3 to 35 lead us to evaluate combinations with ribavirin. Combinations of ribavirin and chloroquine or chlorpromazine were synergistic against CCHFV. Though the low chlorpromazine selectivity index suggests the need for a chemical improvement, our present study highlights chloroquine as the main drug having the potential for drug repurposing.


title: Canine Influenza

text: Canine influenza, as a recognized clinical entity in dogs, has a relatively brief history. The presence of specific subtypes of influenza virus capable of being transmitted from dog to dog is at present geographically limited to the United States and Korea. As surveillance intensifies to meet the concerns of the human population on pandemic influenza viruses, more cases of influenza virus in dogs are certain to be detected. Each infection offers an opportunity for a unique variant to emerge and continue the evolution of influenza virus as a species-crossing pathogen.