title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?

text: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.


title: Methodology for assessment of public health emergency preparedness and response synergies between institutional authorities and communities

text: BACKGROUND: This paper describes a participatory methodology that supports investigation of the synergistic collaboration between communities affected by infectious disease outbreak events and relevant official institutions. The core principle underlying the methodology is the recognition that synergistic relationships, characterised by mutual trust and respect, between affected communities and official institutions provide the most effective means of addressing outbreak situations. METHODS: The methodological approach and lessons learned were derived from four qualitative case studies including (i) two tick-borne disease events (Crimean-Congo haemorrhagic fever in Spain, 2016, and tick-borne encephalitis in the Netherlands, 2016); and (ii) two outbreaks of acute gastroenteritis (norovirus in Iceland, 2017, and verocytotoxin-producing Escherichia coli [VTEC] in Ireland, 2018). An after-event qualitative case study approach was taken using mixed methods. The studies were conducted in collaboration with the respective national public health authorities in the affected countries by the European Centre for Disease Prevention and Control (ECDC). The analysis focused on the specific actions undertaken by the participating countries’ public health and other authorities in relation to community engagement, as well as the view from the perspective of affected communities. RESULTS: Lessons highlight the critical importance of collaborating with ECDC National Focal Points during preparation and planning and with anthropological experts. Field work for each case study was conducted over one working week, which although limiting the number of individuals and institutions involved, still allowed for rich data collection due to the close collaboration with local authorities. The methodology enabled efficient extraction of synergies between authorities and communities. Implementing the methodology required a reflexivity among fieldworkers that ackowledges that different versions of reality can co-exist in the social domain. The method allowed for potential generalisability across studies. Issues of extra attention included insider-outsider perspectives, politically sensitivity of findings, and how to deal with ethical and language issues. CONCLUSIONS: The overall objective of the assessment is to identify synergies between institutional decision-making bodies and community actors and networks before, during and after an outbreak response to a given public health emergency. The methodology is generic and could be applied to a range of public health emergencies, zoonotic or otherwise.


title: Feline Virome—A Review of Novel Enteric Viruses Detected in Cats

text: Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.


title: Structural Flexibility of the Pentameric SARS Coronavirus Envelope Protein Ion Channel

text: Coronaviruses contain a small envelope membrane protein with cation-selective ion channel activity mediated by its transmembrane domain (ETM). In a computational study, we proposed that ion channel activity can be explained by either of two similar ETM homopentameric transmembrane α-helical bundles, related by a ∼50° rotation of the helices. Later, we tested this prediction, using site-specific infrared dichroism of a lysine-flanked isotopically labeled ETM peptide from the virus responsible for the severe acute respiratory syndrome, SARS, reconstituted in lipid bilayers. However, the data were consistent with the presence of a kink at the center of the ETM α-helix, and it did not fit completely either computational model. Herein, we have used native ETM, without flanking lysines, and show that the helix orientation is now consistent with one of the predicted models. ETM only produced one oligomeric form, pentamers, in the lipid-mimic detergent dodecylphosphocholine and in perfluorooctanoic acid. We thus report the correct backbone model for the pentameric α-helical bundle of ETM. The disruptive effects caused by terminal lysines probably highlight the conformational flexibility required during ion channel function.


title: Organoid culture systems to study host–pathogen interactions

text: Recent advances in host–microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered. Here we discuss the most recent and striking studies on host–microbe interactions in organoid cultures, highlighting various methods which can be used for developing microbe-organoid co-culture systems.


title: Fluorogenic RT–PCR assay (TaqMan) for detection and classification of bovine viral diarrhea virus

text: Abstract A single tube fluorogenic RT–PCR-based ‘TaqMan’ assay was developed for detection and classification of bovine viral diarrhea virus (BVDV). TaqMan–PCR was optimized to quantify BVD virus using the ABI PRISM 7700 sequence detection system and dual-labeled fluorogenic probes. Two different gene specific labeled fluorogenic probes for the 5′ untranslated region (5′ UTR) were used to differentiate between BVD types I and II. Sensitivity of the single tube TaqMan assay was compared with two-tube TaqMan assay and standard RT–PCR using 10-fold dilutions of RNA. Single tube TaqMan assay was 10–100-fold more sensitive than the two-tube TaqMan assay and the standardized single tube RT–PCR. Specificity of the assay was evaluated by testing different BVD virus strains and other bovine viruses. A total of 106 BVD positive and negative pooled or single serum samples, field isolates and reference strains were tested. Quantitation of cRNA from types I and II BVD virus was accomplished by a standard curve plotting cycle threshold values (C T) versus copy number. Single tube TaqMan–PCR assay was sensitive, specific and rapid for detection, quantitation and classification of BVD virus.


title: Current literature in mass spectrometry

text: In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books, Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (6 Weeks journals ‐ Search completed at 4th. Oct. 2006)


title: The prophylactic effect of different levels of positive endexpiratory pressure on the incidence rate of atelectasis after cardiac surgery: A Randomized Controlled Trial

text: Background: The use of positive end-expiratory pressure (PEEP) can have an important role as one of the ways to prevent and treat atelectasis, but it seems that there is still no consensus about its beneficial level. The aim of this study was to determine the effect of different levels of PEEP on the incidence of atelectasis after heart surgery. Methods: This is a double-blind randomized controlled trial that was adopted from a research project recorded in the Iranian Registry of Clinical Trials. This paper is the result of a research project undertaken at Fatemeh Zahra Hospital (Mazandaran Heart Center) in 2015. 180 patients underwent open heart surgery were selected and were divided randomly into three groups: control, PEEP=8, and PEEP=10 (60 in each group). The patients in the two PEEP8 and PEEP10 intervention groups separately received 8 cm H2O and 10 cm H2O PEEP, respectively, 30 minutes after admission to the ICU for 4 hours and then received 5 cm H2O PEEP until extubation. Atelectasis was examined two hours after the extubation and on the third day after surgery. Results: The incidence rates of atelectasis two hours after extubation on the first day of surgery were 22 (36.7%), 20 (33.3%) and 10 (16.7%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were statistically significant among the three groups (p=0.035). The incidence rates of atelectasis on the third day after surgery were 39 (65%), 36 (60%) and 21 (35%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were also statistically significant among the three groups (p=0.003). Conclusion: The use of 10 cm H2O PEEP can lead to a reduction in the incidence of atelectasis, intubation time at the ICU and length of ICU and hospital stay. Given that this level of PEEP is effective, this method is recommended to be used in postoperative care of patients.


title: Hindsight: A re-analysis of the severe acute respiratory syndrome outbreak in Beijing

text: Summary Objective To review the severe acute respiratory syndrome (SARS) epidemic in Beijing using basic epidemiological principles omitted from the original analysis. Study design Analysis of Prospective surveillance data for Beijing collected during the outbreak. Methods Surveillance data were reclassified according to World Health Organization criteria. Cases previously excluded without date of onset of illness were included in the epidemic curve from estimates using the average time between date of onset and date of hospitalization for cases with both dates. Cases who failed to give a contact history were now included; 7% ( n = 5 ) of cases during the import phase and 61% ( n = 365 ) during the peak phase. Previously excluded cases were included for plotting on an epidemic curve, and basic spot mapping for distribution of cases was used from attack rates recalculated for age, gender, occupation, residential location, date of onset of illness and demographics. Results The spot map effectively illustrated clusters by residency, with the inner-city sustaining the highest attack rate (33.42 per 100,000), followed by an easterly distribution 5–30km away (21.62 per 10,000), and lowest in districts 60–160km away (9.21 per 100,000). The new epidemic curve shows the outbreak commencing 10 days earlier than initially reported, with a three-fold greater increase in cases during the escalation phase than previously estimated. Conclusion In hindsight, the investigation of the Beijing SARS would have benefited from the use of spot maping as an essential outbreak tool for early identification of specific geographical area(s) for quarantining. If a spot map of incidence density rates was used during the early phase of the outbreak, the inner city might have been identified as a major risk factor requiring rapid quarantining. Contact history became uncommon as the outbreak progressed, suggesting that hospitals were over-burdened or pathogenesis and environment risk factors changed, strengthening the usefulness of early spot mapping and the need to modify risk factors included as contact history as the epidemic progresses.


title: Molecular epidemiology and phylogenetic analysis of diverse bovine astroviruses associated with diarrhea in cattle and water buffalo calves in China

text: Astroviruses are the principal causative agents of gastroenteritis in humans and have been associated with diarrhea in other mammals as well as birds. However, astroviral infection of animals had been poorly studied. In the present study, 211 rectal swabs collected from cattle and water buffalo calves with mild to severe diarrhea were tested for bovine astrovirus (BAstV) by RT-PCR. Results: 92/211 (43.6%) samples were positive for BAstV, at a rate of 46.10% (71/154) in cattle and 36.84% (21/57) in water buffalo. Phylogenetic analysis based on the partial and full-length of 25 ORF2 amino acid sequences obtained in this study classified the Guangxi BAstVs isolates into five subgroups under the genus of Mamastrovirus, genotype MAstV33, which suggested that the water buffalo was a new host of this genogroup that previously included only cattle and roe deer. Despite the origin of the host, the Guangxi BAstV isolates were closely related to the BAstV Hong Kong isolates (B18/HK and B76-2/HK), but highly divergent from the BAstV NeuroS1 isolate previously associated with neurologic disease in cattle in the U.S.A. Nucleotide sequence-based characterization of the ORF1b/ORF2 junction and corresponding overlapping regions showed distinctive properties, which may be common to BAstVs. Our results suggested that cattle and water buffalo are prone to infection of closely related astroviruses, which probably evolved from the same ancestor. The current study described astroviruses in water buffalo for the first time and is thus far among the largest epidemiological investigations of BAstV infection in cattle conducted in China.


title: Enzyme-linked immunosorbent assay for the detection of the coronavirus-like agent and its antibodies in pigs with porcine epidemic diarrhea

text: Abstract An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the coronavirus-like agent in feces of pigs naturally affected with porcine epidemic diarrhea (PED) or experimentally infected with the CV777 isolate. The assay was specific and more sensitive than electron microscopy. An ELISA blocking assay is described for the detection and titration of antibodies. Specific antibody formation was demonstrated in pigs experimentally infected with CV777 and in swine naturally affected with PED.


title: Histophilosis as a Natural Disease

text: Histophilus somni is responsible for sporadic disease worldwide in cattle and, to a lesser extent, in small ruminants, bighorn sheep (Ovis canadensis), and North American bison (Bison bison). The importance of H. somni diseases can be attributed to improved clinical and laboratory recognition, combined with the growth in intensive management practices for cattle. Although outbreaks of bovine histophilosis can occur year-round, in northern and southern hemispheres, it is most frequent in late fall and early winter. Weather, stress, dietary changes, and comingling of cattle are likely to be major triggers for outbreaks. The most frequent clinical expressions of histophilosis include undifferentiated fever, fibrinosuppurative pneumonia, encephalitis-leptomeningitis, necrotizing myocarditis, and diffuse pleuritis. Neurological disease occurs either as thrombotic meningoencephalitis (TME) or as suppurative meningitis with ventriculitis. Acute myocarditis is characteristically necrotizing and generally involves one or both papillary muscles in the left ventricular myocardium. Biofilm-like aggregates of bacteria occur in capillaries and veins in myocardium, in the central nervous system, and on endocardial surfaces. H. somni is a component of bovine respiratory disease (BRD) complex. In our experience, it is most commonly diagnosed in subacute-to-chronic polymicrobial pulmonary infections in combination with Mannheimia haemolytica, Trueperella pyogenes, Pasteurella multocida, or Mycoplasma bovis. Other, less common forms of H. somni disease present as polyarthritis/tenosynovitis, abortion with placentitis and fetal septicemia, epididymitis-orchitis, and ocular infections. It is likely that H. somni is under-recognized clinically and diagnostically. Most state and provincial laboratories in North America rely on bacterial isolation to confirm infection. The use of more sensitive detection methods on field cases of histophilosis will help resolve the pathogenesis of H. somni in natural outbreaks, and whether the disease is as common elsewhere as it is in Canada.


title: Triterpenoids from the stems of Tripterygium regelii

text: Abstract Three new triterpenoids, triregelolides A, B (1, 2), and triregeloic acid (3), were isolated from the stems of Tripterygium regelii along with twenty known triterpene analogues (4–23). The structures of three new compounds were identified by analyzing their NMR spectroscopic and HRESIMS data. Compounds 4, 7, 8, 10, 13, 14, 17, 21–23 were isolated from T. regelii for the first time. Compounds 3, 5, 6, 8, 9, 10, 14 and 16 showed inhibitory effects on the proliferation of human breast cancer cells MCF-7 by 24.1%, 69.6%, 72.8%, 21.6%, 23.1%, 43.3%, 25.5% and 23.5% (p <0.05) at a concentration of 10μM, respectively.


title: Sore throat in COVID‐19: Comment on “Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis”

text: We read with interest the recent meta-analysis by Sun et al.1 that included 50466 patients with Coronavirus Disease 2019 (COVID-19). The author found that fever and cough were the most common symptoms, and several subjects had muscle soreness or fatigue. In addition, they reported that "by reading the included literature, we found that diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare".1 This article is protected by copyright. All rights reserved.


title: The New Public Health Hegemony: Response to Severe Acute Respiratory Syndrome (SARS) in Toronto

text: The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak presented a challenging period for public health in Toronto. Many old and new public health measures were implemented at local, national and global levels, in an attempt to control the outbreak of the disease. Among these, surveillance mechanisms dominated, which involved new epidemiological techniques and statistical profiling strategies. In this paper, Gramsci's concept of hegemony is used to further understandings of public health governance during the outbreak of emerging infectious diseases. Specifically, the function of the discourse of ‘risk’ in public health governance is examined, along with public health as a ‘moral agent’ in the naturalization of specific public health measures. In addition, the pervasive discourse of ‘security’ is discussed in relation to current public health practices. These characteristics of public health are examined with consideration of their potential for propagating social exclusion and stigmatization of individuals and communities. The specific case of SARS in Toronto is used to examine the implications of public health as a mechanism for social control and reproduction rather than the promotion of equality in health throughout the population.


title: Forecasting the incidence of tuberculosis in China using the seasonal auto-regressive integrated moving average (SARIMA) model

text: Abstract Objectives The aims of this study were to develop a forecasting model for the incidence of tuberculosis (TB) and analyze the seasonality of infections in China; and to provide a useful tool for formulating intervention programs and allocating medical resources. Methods Data for the monthly incidence of TB from January 2004 to December 2015 were obtained from the National Scientific Data Sharing Platform for Population and Health (China). The Box–Jenkins method was applied to fit a seasonal auto-regressive integrated moving average (SARIMA) model to forecast the incidence of TB over the subsequent six months. Results During the study period of 144 months, 12,321,559 TB cases were reported in China, with an average monthly incidence of 6.4426 per 100,000 of the population. The monthly incidence of TB showed a clear 12-month cycle, and a seasonality with two peaks occurring in January and March and a trough in December. The best-fit model was SARIMA (1,0,0)(0,1,1)12, which demonstrated adequate information extraction (white noise test, p> 0.05). Based on the analysis, the incidence of TB from January to June 2016 were 6.6335, 4.7208, 5.8193, 5.5474, 5.2202 and 4.9156 per 100,000 of the population, respectively. Conclusions According to the seasonal pattern of TB incidence in China, the SARIMA model was proposed as a useful tool for monitoring epidemics.


title: The Cell Biology of Acute Childhood Respiratory Disease: Therapeutic Implications

text: Respiratory syncytial virus (RSV), the recently identified human metapneumovirus (HMPV), and the human parainfluenza viruses (HPIVs), cause most cases of childhood croup, bronchiolitis, and pneumonia. Influenza virus also causes a significant burden of disease in young children, although its significance in children was not fully recognized until recently. This article discusses pathogens that have been studied for several decades, including RSV and HPIVs, and also explores the newly identified viral pathogens HMPV and human coronavirus NL63. The escalating rate of emergence of new infectious agents, fortunately meeting with equally rapid advancements in molecular methods of surveillance and pathogen discovery, means that new organisms will soon be added to the list. A section on therapies for bronchiolitis addresses the final common pathways that can result from infection with diverse pathogens, highlighting the mechanisms that may be amenable to therapeutic approaches. The article concludes with a discussion of the overarching impact of new diagnostic strategies.


title: Pulsed xenon ultraviolet and non-thermal atmospheric plasma treatments are effective for the disinfection of air in hospital blood sampling rooms

text: Abstract Background and objectives Non-thermal atmospheric plasma treatment and pulsed xenon ultraviolet (PX-UV) treatment are widely used in disinfection of hospital environments. However, their effectiveness has not been evaluated against a comparator. The objective of this study is to evaluate their effectiveness in the disinfection of pathogens in the air in hospital blood sampling rooms. Methods Samples were taken from the air before and after disinfection with PX-UV and non-thermal atmospheric plasma. We counted bacterial colonies and identified the types of bacteria. Results Non-thermal plasma treatment significantly reduced bacterial counts in the air, the median reduced from 1 before treatment to zero afterwards (p = 0.03). PX-UV treatment also significantly reduced bacterial counts in the air (p = 0.01), the median reduced from 1.5 before treatment to zero afterwards. Pathogens identified in the current study include nosocomial bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, and yeast. Conclusion Disinfection of blood sampling sites is essential in a health service department. The efficiency of PX-UV and non-thermal atmospheric plasma treatment are comparable in air disinfection.


title: Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases

text: Abstract Objectives. To describe the clinical characteristics and outcomes of patients with severe acute respiratory syndrome (SARS). Methods. Between March 28 and June 30 '2003, 29 patients with probable SARS seen at Shin Kong Wu Ho-Su Memorial Hospital, Taipei, were analysed. Results. Presenting symptoms included fever (100%), cough (69.0%), chills or rigor (62.1%), and shortness of breath (41.4%). Mean days to defervescence were 6.8±2.9 days, but fever recurred in 15 patients (51.7%) at 10.9±3.4 days. Common laboratory features included lymphopenia (72.4%), thrombocytopenia (34.5%) and elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) (93.1, 62.1, 44.8%, respectively). All patients except one had initial abnormal chest radiographs and 20 (69.0%) had radiological worsening at 7.5±2.6 days. Nine patients (31.0%) subsequently required mechanical ventilation with four deaths (13.8%). Most patients with clinical deterioration responded to pulse corticosteroid therapy (14 out of 17) but six complicated with nosocomial infections. The risk factors associated with severe disease were presence of diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and high peak values. Conclusions. Prudent corticosteroid use, vigilant microbiological surveillance and appropriate antibiotics coverage are the key to successful treatment.


title: The role of adipocytes and adipocyte‐like cells in the severity of COVID‐19 infections

text: Coronavirus disease‐2019 (COVID‐19), caused by the highly pathogenic virus SARS‐CoV‐2, demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis (PF). In this Perspective, we argue that adipocytes and adipocyte‐like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to COVID‐19. Expression of angiotensin‐converting enzyme 2 (ACE2 ‐ the functional receptor for SARS‐CoV) ‐ is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID‐19 infections. Similar to the recently established adipocyte‐myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF. This may significantly increase the severity of the local response to COVID‐19 in the lung. To reduce the severity and mortality with COVID‐19, we propose to probe for the clinical response to thiazolidinediones (TZDs), PPARγ agonists, that are the well‐known anti‐diabetic drugs. TZDs are able to stabilize lipofibroblasts in their “inactive” state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.


title: Scoping review sobre las recomendaciones para el aislamiento domiciliario en la pandemia del COVID-19

text: RESUMEN La pandemia COVID-19 ha afectado a países de todos los continentes donde se ha aplicado de forma sistemática medidas de confinamiento y aislamiento. Objetivo: Sintetizar la evidencia disponible sobre el manejo del aislamiento domiciliario por infección de COVID-19. Método: Se ha realizado una scoping review consultando mediante lenguaje controlado Trip Database, PUBMED, CINAHL, COCHRANE y Elsevier sin ningún tipo de límites. De todos los documentos localizados se extrajo información sobre la fecha de publicación, país de publicación, tipo de estudio, valoración del nivel de evidencia y grado de recomendación y resultados de interés para responder a la pregunta de investigación. Se ha realizado lectura crítica de los documentos seleccionados, pero sin utilizarla como criterio de exclusión sino informativo. Resultados: Se localizaron 163 registros y se han seleccionado 14. Las recomendaciones se han agrupado en 10 temas alrededor de todo el manejo cotidiano de un cuidado en domicilio. Conclusiones: Se objetiva la escasez de evidencias robustas sobre el aislamiento ante la infección del COVID-19. La mayoría de los documentos son revisiones realizadas tras el consenso de expertos a nivel internacional. ABSTRACT The COVID-19 pandemic has affected countries on all continents where containment and isolation measures have been systematically applied. Aim: To synthesize the available evidence on the management of home isolation due to COVID-19 infection. Method: A scoping review has been carried out using the Trip Database, PUBMED, CINAHL, COCHRANE and Scopus controlled language without any limits. From all the documents located, information was extracted on the date of publication, country of publication, type of study, assessment of the level of evidence and degree of recommendation, and results of interest to answer the research question. Critical reading of the selected documents has been carried out, but without using it as an exclusion criterion but rather informative. Results: 163 records were located and 14 were selected. The recommendations have been grouped into 10 topics around all the daily management of home care. Conclusions: The scarcity of robust evidence on isolation from COVID-19 infection is objective. Most of the documents are reviews carried out after the consensus of experts at the international level.


title: Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles

text: The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect.


title: Cognitive‐behavioral therapy in the time of coronavirus: Clinician tips for working with eating disorders via telehealth when face‐to‐face meetings are not possible

text: OBJECTIVE: The coronavirus pandemic has led to a dramatically different way of working for many therapists working with eating disorders, where telehealth has suddenly become the norm. However, many clinicians feel ill equipped to deliver therapy via telehealth, while adhering to evidence‐based interventions. This article draws together clinician experiences of the issues that should be attended to, and how to address them within a telehealth framework. METHOD: Seventy clinical colleagues of the authors were emailed and invited to share their concerns online about how to deliver cognitive‐behavioral therapy for eating disorders (CBT‐ED) via telehealth, and how to adapt clinical practice to deal with the problems that they and others had encountered. After 96 hr, all the suggestions that had been shared by 22 clinicians were collated to provide timely advice for other clinicians. RESULTS: A range of themes emerged from the online discussion. A large proportion were general clinical and practical domains (patient and therapist concerns about telehealth; technical issues in implementing telehealth; changes in the environment), but there were also specific considerations and clinical recommendations about the delivery of CBT‐ED methods. DISCUSSION: Through interaction and sharing of ideas, clinicians across the world produced a substantial number of recommendations about how to use telehealth to work with people with eating disorders while remaining on track with evidence‐based practice. These are shared to assist clinicians over the period of changed practice.


title: Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response

text: The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-cell PCR cloning of E-binding monoclonal antibodies for analysing antibody response in a patient from the early stages of infection to more than one year after the clearance of the virus. The patient's IgH repertoire 14 and 64 days after symptom onset showed dramatic dominant clonal expansion but low clonal diversity. IgH repertoire 6 months after disease-free status had few dominant clones but increased diversity. E-binding antibodies appeared abundantly in the repertoire during the early stages of infection but quickly declined after clearance of the virus. Certain VH genes such as VH5-10-1 and VH4-39 appeared to be preferentially enlisted for a rapid antibody response to ZIKV infection. Most of these antibodies require relatively few somatic hypermutations to acquire the ability to bind to the E protein, pointing to a possible mechanism for rapid defence against ZIKV infection. This study provides a unique and holistic view of the dynamic changes and characteristics of the antibody response to ZIKV infection.


title: The antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus

text: BACKGROUND: The 2003 outbreak of severe acute respiratory syndrome (SARS) infected over 8000 people and killed 774. Transmission of SARS occurred through direct and indirect contact and large droplet nuclei. The World Health Organization recommended the use of household disinfectants, which have not been previously tested against SARS coronavirus (SARS-CoV), to disinfect potentially contaminated environmental surfaces. There is a need for a surrogate test system given the limited availability of the SARS-CoV for testing and biosafety requirements necessary to safely handle it. In this study, the antiviral activity of standard household products was assayed against murine hepatitis virus (MHV), as a potential surrogate for SARS-CoV. METHODS: A surface test method, which involves drying an amount of virus on a surface and then applying the product for a specific contact time, was used to determine the virucidal activity. The virus titers and log reductions were determined by the Reed and Muench tissue culture infective dose (TCID)(50) end point method. RESULTS: When tested as directed, common household disinfectants or antiseptics, containing either 0.050% of triclosan, 0.12% of PCMX, 0.21% of sodium hypochlorite, 0.23% of pine oil, or 0.10% of a quaternary compound with 79% of ethanol, demonstrated a 3-log reduction or better against MHV without any virus recovered in a 30-second contact time. CONCLUSION: Common household disinfectants and antiseptics were effective at inactivating MHV, a possible surrogate for SARS-CoV, from surfaces when used as directed. In an outbreak caused by novel agents, it is important to know the effectiveness of disinfectants and antiseptics to prevent or reduce the possibility of human-to-human transmission via surfaces.


title: Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China

text: Summary Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China’s most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province’s large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.


title: Full-Length Genome Sequence of Porcine Epidemic Diarrhea Virus Strain CH/GX/2015/750A

text: We report here the complete genome sequence of porcine epidemic diarrhea virus (PEDV) strain CH/GX/2015/750A (750A), which was isolated from a suckling piglet with watery diarrhea in Guangxi, China. The isolate is genetically close to other recent Chinese variant PEDVs and distinct from the classical PEDVs.


title: Isolation and rapid sharing of the 2019 novel coronavirus (SARS‐CoV‐2) from the first patient diagnosed with COVID‐19 in Australia

text: OBJECTIVES: To describe the first isolation and sequencing of SARS‐CoV‐2 in Australia and rapid sharing of the isolate. SETTING: SARS‐CoV‐2 was isolated from a 58‐year‐old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID‐19 (the illness caused by SARS‐CoV‐2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS‐CoV‐2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS‐CoV‐2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS‐CoV‐2 genomes. Within 24 hours of isolation, the first Australian SARS‐CoV‐2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS‐CoV‐2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.


title: Diagnostic performance between CT and initial real-time RT-PCR for clinically suspected 2019 coronavirus disease (COVID-19) patients outside Wuhan, China

text: Abstract Introduction Chest CT is thought to be sensitive but less specific in diagnosing the 2019 coronavirus disease (COVID-19). The diagnostic value of CT is unclear. We aimed to compare the performance of CT and initial RT-PCR for clinically suspected COVID-19 patients outside the epicentre—Wuhan, China. Materials and methods Patients clinically suspected of COVID-19 infection who underwent initial RT-PCR and chest CT at the same time were retrospectively enrolled. Two radiologists with specific training reviewed the CT images independently and final diagnoses of the presence or absence of COVID-19 was reached by consensus. With serial RT-PCR as reference standard, the performance of initial RT-PCR and chest CT was analysed. A strategy of combining initial RT-PCR and chest CT was analysed to study the additional benefit. Results 82 patients admitted to hospital between Jan 10, 2020 to Feb 28, 2020 were enrolled. 34 COVID-19 and 48 non-COVID-19 patients were identified by serial RT-PCR. The sensitivity, specificity was 79% (27/34) and 100% (48/48) for initial RT-PCR and 77% (26/34) and 96% (46/48) for chest CT. The image readers had a good interobserver agreement with Cohen's kappa of 0.69. No statistical difference was found in the diagnostic performance between initial RT-PCR and chest CT. The comprehensive strategy had a higher sensitivity of 94% (32/34). Conclusions Initial RT-PCR and chest CT had comparable diagnostic performance in identification of suspected COVID-19 patients outside the epidemic center. To compensate potential risk of false-negative PCR, chest CT should be applied for clinically suspected patients with negative initial RT-PCR.


SARS attacks!


title: IFITM proteins inhibit HIV-1 protein synthesis

text: Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.


title: Cyclophilin A and viral infections

text: Abstract Cyclophilin A (CyPA) is a peptidyl-prolyl cis/trans isomerase originally identified as the target of the immunosuppressive drug cyclosporine A. A number of reports have demonstrated that CyPA plays a critical role in the successful replication of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), etc. However, recent studies demonstrated that CyPA also possesses a repressive effect on the replication of some viruses like Influenza A virus and rotavirus. Moreover, CyPA could also regulate host IFN-I response to viral infections. Together, these evidences showed diverse roles of CyPA in viral infection.


title: Expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome-associated coronavirus

text: SARS 8b is one of the putative accessory proteins of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) with unknown functions. In this study, the cellular localization and activity of this estimated 9.6 kDa protein were examined. Confocal microscopy results indicated that SARS 8b is localized in both nucleus and cytoplasm of mammalian cells. Functional study revealed that overexpression of SARS 8b induced DNA synthesis. Coexpression of SARS 8b and SARS 6, a previously characterized SARS-CoV accessory protein, did not elicit synergistic effects on DNA synthesis.


Personalized Cancer Supportive Care in COVID-19 Era


title: Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications

text: Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. Objective To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. Design, setting, and participants Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. Outcome measurements and statistical analysis Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. Results and limitations Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. Conclusions Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. Patient summary We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.


title: New strategy for virus discovery: viruses identified in human feces in the last decade

text: Emerging and re-emerging viruses continue to surface all over the world. Some of these viruses have the potential for rapid and global spread with high morbidity and mortality, such as the SARS coronavirus outbreak. It is extremely urgent and important to identify a novel virus near-instantaneously to develop an active preventive and/or control strategy. As a culture-independent approach, viral metagenomics has been widely used to investigate highly divergent and completely new viruses in humans, animals, and even environmental samples in the past decade. A new model of Koch’s postulates, named the metagenomic Koch’s postulates, has provided guidance for the study of the pathogenicity of novel viruses. This review explains the viral metagenomics strategy for virus discovery and describes viruses discovered in human feces in the past 10 years using this approach. This review also addresses issues related to the metagenomic Koch’s postulates and the challenges for virus discovery in the future.


title: Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits

text: ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction.


title: Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

text: BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. AIM: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. METHODS: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. RESULTS: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium. CONCLUSION: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.


title: Suppression of Drug Resistance in Dengue Virus

text: Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of “dominant drug targets,” in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection.


title: Proteomic analysis of cathepsin B and L-deficient mouse brain lysosomes

text: Abstract Cathepsins B and L are lysosomal cysteine proteases which have been implicated in a variety of pathological processes such as cancer, tumor angiogenesis, and neurodegeneration. However, only a few protein substrates have thus far been described and the mechanisms by which cathepsins B and L regulate cell proliferation, invasion, and apoptosis are poorly understood. Combined deficiency of both cathepsins results in early-onset neurodegeneration in mice reminiscent of neuronal ceroid lipofuscinoses in humans. Therefore, we intended to quantify accumulated proteins in brain lysosomes of double deficient mice. A combination of subcellular fractionation and LC-MS/MS using isobaric tagging for relative and absolute quantitation (iTRAQ™) allowed us to simultaneously assess wildtype and cathepsin B−/−L−/− cerebral lysosomes. Altogether, 19 different proteins were significantly increased in cathepsin B−/−L−/− lysosomes. Most elevated proteins had previously been localized to neuronal biosynthetic, recycling/endocytic or lysosomal compartments. A more than 10-fold increase was observed for Rab14, the Delta/Notch-like epidermal growth factor-related receptor (DNER), calcyon, and carboxypeptidase E. Intriguingly, immunohistochemistry demonstrated that Rab14 and DNER specifically stain swollen axons in double deficient brains. Since dense accumulations of expanded axons are the earliest phenotypic and pathognomonic feature of cathepsin B−/−L−/− brains, our data suggest a role for cathepsins B and L in recycling processes during axon outgrowth and synapse formation in the developing postnatal central nervous system.


title: What evidence-based medicine researchers can do to help clinicians fighting COVID-2019?

text: • The World Health Organization (WHO) has declared COVID-19 pandemic as a global public health emergency. • Research community has responded rapidly, and thousands of articles have been published already in scholarly journals, making it difficult for clinicians to sift through the evidence and find answers. • Methodologist researchers and relevant international organizations have addressed the pandemic immediately. However, these efforts are hindered with avoidable problems and massive duplication of effort. • We believe that research methodologists can be very useful now to clinicians. The COVID-evidence project can be an example of how to establish a living dialogue of methodologists and clinicians to fight COVID-19 pandemic.


title: Epimeric methylsulfinyladenosine derivatives from the marine ascidian Herdmania momus

text: Abstract Investigation of the secondary metabolites of the ascidian Herdmania momus led to the isolation and characterization of four new nucleoside derivatives (1–4). Structural studies showed that these derivatives represent a series of rare methylsulfinyladenosine derivatives of interconvertible transesterification isomers and/or sulfinyl epimers. The antiviral activities of these rare nucleosides were evaluated against a series of human pathogenic viruses.


title: The protein interaction networks of mucolipins and two-pore channels

text: Abstract Background The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While partially compensatory for each other, isoform-specific intracellular distribution, cell-type expression patterns, and regulatory mechanisms suggest different channel isoforms confer distinct properties to the cell. Scope of review Briefly, established TPC/TRPML functions and interaction partners (‘interactomes’) are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted. Accordingly, interactomes are compared and contrasted, and subsequently described in detail for TPC1, TPC2, TRPML1, and TRPML3. Major conclusions TPC interactomes are well-defined, encompassing intracellular membrane organisation proteins. TRPML interactomes are varied, encompassing cardiac contractility- and chaperone-mediated autophagy proteins, alongside regulators of intercellular signalling. General significance Comprising recently proposed targets to treat cancers, infections, metabolic disease and neurodegeneration, the advancement of TPC/TRPML understanding is of considerable importance. This review proposes novel directions elucidating TPC/TRPML relevance in health and disease. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.


title: Protection of human erythrocyte using Crinumasiaticum extract and lycorine from oxidative damage induced by 2-amidinopropane

text: The intention of this investigation was to evaluate the free radical scavenging activity and erythrocyte protective activity of ethanolic extract of Crinumasiaticum (L) and lycorine. The ethanolic extract of C. asiaticum (L) and lycorine were found to have different levels of antioxidant properties in the test models. Both ethanolic extract of C. asiaticum (L) (0.5–2.5 mg/ml) and lycorine (0.010 mg–0.050 mg/ml) increases the percentage of lipid peroxidation inhibition (26.25 ± 0.23% and 19.25 ± 0.23%) and enhances the free radical scavenging activity (20.92 ± 0.22% and 20.52 ± 0.22%), scavenging of hydrogen peroxide (25.67 ± 0.17% and 23.07 ± 0.3%) superoxide anion scavenging activity (27.69 ± 0.16% and 16.09 ± 0.7%) at concentration of 2.5 and 0.050 mg of C. asiaticum (L) and lycorine, respectively. But compared with tocopherol (P < 0.05) less activity was observed by C. asiaticum (L) and lycorine. The ethanolic extract of C. asiaticum (L) and lycorine were normalized to reduce the level of glutathione and also to sustain the status of protein in erythrocytes during the peroxyl radical [2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)] induced oxidative damage in ex vivo model. The present results of the investigations demonstrated that protective nature of the C. asiaticum (L) and lycorine will be considered as a significant natural antioxidant source.


Middle East Respiratory Syndrome (MERS) coronavirus. What travel health advice should be given to Hajj pilgrims?


A global recommendation for restrictive provision of fertility treatments during the COVID‐19 pandemic


title: Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

text: Abstract Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5′ cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent inhibitor of cap-dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells. EC50 values of 1.3 nM and 3 nM silvestrol were determined for MERS-CoV and HCoV-229E, respectively. For the highly pathogenic MERS-CoV, the potent antiviral activities of silvestrol were also confirmed using peripheral blood mononuclear cells (PBMCs) as a second type of human primary cells. Silvestrol strongly inhibits the expression of CoV structural and nonstructural proteins (N, nsp8) and the formation of viral replication/transcription complexes. Furthermore, potential antiviral effects against human rhinovirus (HRV) A1 and poliovirus type 1 (PV), representing different species in the genus Enterovirus (family Picornaviridae), were investigated. The two viruses employ an internal ribosomal entry site (IRES)-mediated translation initiation mechanism. For PV, which is known to require the activity of eIF4A, an EC50 value of 20 nM silvestrol was determined in MRC-5 cells. The higher EC50 value of 100 nM measured for HRV A1 indicates a less critical role of eIF4A activity in HRV A1 IRES-mediated translation initiation. Taken together, the data reveal a broad-spectrum antiviral activity of silvestrol in infected primary cells by inhibiting eIF4A-dependent viral mRNA translation.


title: Fit for the future? The place of global health in the UK's postgraduate medical training: a review

text: OBJECTIVES: That health is now global is increasingly accepted. However, a ‘mismatch between present professional competencies and the requirements of an increasingly interdependent world’ has been identified. Postgraduate training should take account of the increasingly global nature of health; this paper examines the extent to which they currently do. DESIGN: Trainees across 11 medical specialties reviewed the content of their postgraduate curriculum. SETTING: Not relevant. PARTCIPANTS: None. MAIN OUTCOME MEASURES: Competencies were coded as ‘UK’ (statement only relevant to UK work), ‘global’ (statement with an explicit reference to aspects of health outside the UK) or generic (relevant both to the UK and international settings). RESULTS: Six of the 11 curricula reviewed contained global health competencies. These covered the global burden or determinants of disease and appropriate policy responses. Only one College required trainees to ‘be aware of the World Health Organization’, or ‘know the local, national and international structures for health care’. These cross-cutting competencies have applicability to all specialties. All 11 curricula contained generic competencies where a global health perspective and/or experience could be advantageous, e.g. caring for migrant or culturally different patients. CONCLUSION: Trainees in all specialties should achieve a minimum requirement of global health awareness. This can be achieved through a small number of common competencies that are consistent across core curricula. These should lead on from equivalent undergraduate competencies. Addressing the current gap in the global health content of postgraduate medical curricula will ensure that the UK has health professionals that are trained to meet the health challenges of the future.


title: Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012

text: BACKGROUND: Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. METHODS: Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children’s Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing. RESULTS: Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients. CONCLUSIONS: During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection.


title: Identification of hepadnavirus in the sera of cats

text: Hepadnaviruses infect several animal species. The prototype species, human hepatitis B virus (HBV), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. Recently a novel hepadnavirus, similar to HBV, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in Australia. Herewith, a collection of 390 feline serum samples was screened for hepadnavirus. Overall, the virus was identified in 10.8% of the sera with a significantly higher prevalence (17.8%) in the sera of animals with a clinical suspect of infectious disease. Upon genome sequencing, the virus was closely related (97.0% nt identity) to the prototype Australian feline virus Sydney 2016. The mean and median values of hepadnavirus in the feline sera were 1.3 × 10(6) and 2.1 × 10(4) genome copies per mL (range 3.3 × 10(0)–2.5 × 10(7) genome copies per mL). For a subset of hepadnavirus-positive samples, information on the hemato-chemical parameters was available and in 10/20 animals a profile suggestive of liver damage was present. Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV.


title: An e-mental health intervention to support burdened people in times of the COVID-19 pandemic: CoPE It

text: The outbreak of the novel SARS CoV-2-virus (COVID-19) is pushing national and international healthcare systems to their limits. The aspect of mental health issues, which has been neglected (so far) in times of social isolation and governmental restrictions, now demands innovative and situation-based approaches to support psychological burdened people. The developed e-mental health intervention ‘CoPE It’ offers manualized, evidence-based psychotherapeutic/psychological support to overcome psychological distress in times of COVID-19. E-mental health approaches offer great possibilities to support burdened people during the SARS-CoV-2 pandemic effectively.


title: Genetic diversity and recombination within bufaviruses: Detection of a novel strain in Hungarian bats

text: Abstract Bats are important hosts of many viruses and in several cases they may serve as natural reservoirs even for viruses with zoonotic potential worldwide, including Europe. However, they also serve as natural reservoir for other virus groups with important evolutionary relevance and yet unknown zoonotic potential. We performed viral metagenomic analyses on Miniopterus schreibersii bat fecal samples. As a result, a novel parvovirus was detected for the first time in European bats. Although, bufavirus was recently discovered as a novel human infecting parvovirus, here we report sequence data of the first bufavirus from European bats related to human bufaviruses. Based on our sequence data a possible intragenic recombination event was detected within bufaviruses which may serves as an important milestone in their evolution.


title: Analysis of a SARS-CoV-2 infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation

text: Abstract Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject twenty-one days after the onset of clinical disease. Forty-five S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation, with limited clonal expansion and three bound the receptor binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine-design.


title: Two-Year Prospective Study of the Humoral Immune Response of Patients with Severe Acute Respiratory Syndrome

text: In a cohort study of 56 convalescent patients with severe acute respiratory syndrome (SARS), titers of immunoglobulin G (IgG) antibodies and neutralizing antibodies (NAbs) against SARS-associated coronavirus were assessed at regular intervals (at 1, 4, 7, 10, 16, and 24 months after the onset of disease) by use of enzyme-linked immunosorbent assay and neutralization assay. IgG antibody and NAb titers were highly correlated, peaking at month 4 after the onset of disease and decreasing thereafter. IgG antibodies remained detectable in all patients until month 16, and they became undetectable in 11.8% of patients at month 24. The finding that NAbs remained detectable throughout follow-up is reassuring in terms of protection provided against reinfection; however, NAb titers decreased markedly after month 16


title: Feline immunodeficiency virus (FIV) infection leads to increased incidence of feline odontoclastic resorptive lesions (FORL)

text: Abstract Feline odontoclastic resorptive lesions (FORL), previously known as `neck lesions,' are commonly known in domestic, but also in non-domestic cats. They are characterized by odontoclastic resorptive processes, which take place at the dental root and at the periodontium. Chronic inflammation of gingiva and periodontium is believed to be an important etiological factor in the development of FORL. In this context, various feline viruses have been discussed to play a relevant role in the pathogenesis of these lesions. The aim of this project was to determine in a blinded study the incidence of FORL in 10 cats which were infected for several years with feline immunodeficiency virus (FIV), but were otherwise free of feline viral infections (feline leukemia virus, feline calicivirus, feline herpesvirus, feline parvovirus, feline coronavirus, feline syncytium-forming virus). Nine age-matched controls were kept under identical conditions, but free of FIV. Subgingival resorptive lesions were found in six of 10 FIV-positive cats, but in three of nine controls only. FIV-positive cats had significantly more often gingivae with an increased tendency for bleeding upon probing than FIV-negative cats (p=0.0055), and they had slightly more often hyperplastic gingivae (p=0.0867). In conclusion, signs characteristic of FORL such as subgingival lesions, granulomatous or hyperplastic gingivae with a tendency for bleeding, were found significantly more often in FIV-positive cats than in the controls (p=0.0198). Therefore, it was concluded that FIV infection is an important factor for the occurrence of FORL, possibly through immune suppression or changes of the (sub)gingival micro-environment. However, non-infected control cats also showed some evidence of FORL in the absence of all tested viral infections. Therefore, factors other than viral infections must also play a role in the development of FORL in cats.


title: Clinical and genetic analysis of Human Bocavirus in children with lower respiratory tract infection in Taiwan

text: Abstract Background Human Bocavirus (HBoV) is a likely etiologic agent of acute respiratory disease in children. The prevalence of this virus has been studied in several sites worldwide. We conducted the first clinical and molecular study of HBoV in Taiwan at the Centers for Diseases Control, Taiwan. Objectives To investigate the genomic and epidemiologic profiles of HBoV infection in Taiwan. Study design Throat swabs or nasopharyngeal aspirates were obtained from hospitalized pediatric patients with acute lower respiratory tract infections. Specimens negative for other respiratory viruses by molecular screening were examined for HBoV. Results HBoV was the only virus detected in 30 (5.6%) of 531 samples. Of these positive cases, 56.7% were from children less than 2 years old. Two groups of HBoV co-circulated in Taiwan during the study. Results of evolutionary networks evaluation suggest that HBoV might have had an opportunity for interbreeding of viruses and genetic recombinations among the different genes. Conclusion HBoV may have circulated in Taiwan for some time and it appears to be one of the etiological agents responsible for lower respiratory tract infection in children.


title: Base-By-Base: Single nucleotide-level analysis of whole viral genome alignments

text: BACKGROUND: With ever increasing numbers of closely related virus genomes being sequenced, it has become desirable to be able to compare two genomes at a level more detailed than gene content because two strains of an organism may share the same set of predicted genes but still differ in their pathogenicity profiles. For example, detailed comparison of multiple isolates of the smallpox virus genome (each approximately 200 kb, with 200 genes) is not feasible without new bioinformatics tools. RESULTS: A software package, Base-By-Base, has been developed that provides visualization tools to enable researchers to 1) rapidly identify and correct alignment errors in large, multiple genome alignments; and 2) generate tabular and graphical output of differences between the genomes at the nucleotide level. Base-By-Base uses detailed annotation information about the aligned genomes and can list each predicted gene with nucleotide differences, display whether variations occur within promoter regions or coding regions and whether these changes result in amino acid substitutions. Base-By-Base can connect to our mySQL database (Virus Orthologous Clusters; VOCs) to retrieve detailed annotation information about the aligned genomes or use information from text files. CONCLUSION: Base-By-Base enables users to quickly and easily compare large viral genomes; it highlights small differences that may be responsible for important phenotypic differences such as virulence. It is available via the Internet using Java Web Start and runs on Macintosh, PC and Linux operating systems with the Java 1.4 virtual machine.


title: Prevalence of enteropathogens in cats with and without diarrhea in four different management models for unowned cats in the southeast United States

text: Abstract The objective of this study was to determine the prevalence of enteropathogens in cats with and without diarrhea in four different models for managing unowned cats: short-term animal shelter, long-term sanctuary, home-based foster care, and trap-neuter-return. Fecal samples from 482 cats, approximately half of the cats with normal fecal consistency and half with diarrhea, were tested by zinc sulfate centrifugation and by real-time PCR for a panel of enteropathogens. At least one enteropathogen of feline or zoonotic importance was detected in a majority of cats, regardless of management model. For most enteropathogens, the presence or absence of diarrhea was not significantly associated with infection, the exceptions being Tritrichomonas foetus in sanctuary cats with diarrhea (26%) and normal fecal consistency (10%), respectively (P ≤0.04), and feline coronavirus in foster cats (80% and 58%) (P ≤0.001). The types of enteropathogens detected were related to the type of management model, e.g., viral and protozoal infections were most common in shelters, sanctuaries, and foster homes (confinement systems), whereas helminth infections were most common in trap-neuter-return programs (free-roaming cats). These results suggest that management practices for unowned cats are inadequate for control of enteropathogens and that the presence of diarrhea is a poor indicator of enteropathogen carriage. Risk-management strategies to reduce transmission to people and other animals should focus on sanitation, housing, compliance with preventive care guidelines, periodic surveillance, response to specific enteropathogens, humane population management of free-roaming community cats, public health education, and minimizing the duration and number of cats in mass confinement.


title: Angiotensin receptor blockers and COVID-19

text: Abstract Angiotensin Receptor Blockers (ARBs) exhibit major pleiotropic protecting effects beyond their antihypertensive properties, including reduction of inflammation. ARBs directly protect the lung from the severe acute respiratory syndrome as a result of viral infections, including those from coronavirus. The protective effect of ACE2 is enhanced by ARB administration. For these reasons ARB therapy must be continued for patients affected by hypertension, diabetes and renal disease, comorbidities of the current COVID-19 pandemic. Controlled clinical studies should be conducted to determine whether ARBs may be included as additional therapy for COVID-19 patients.


title: Surgical treatment of diabetic foot ulcers during the COVID-19 pandemic in China

text: Abstract Diabetic foot ulcers are among the most serious complications of diabetes. If left untreated, these ulcers can lead to severe infection and gangrene; in some instances, they may result in death. Thus, timely treatment of diabetic foot ulcers is extremely important. However, timely patient treatment during the COVID-19 pandemic is particularly challenging, because of the higher volume of patients and the need to ensure safety of medical personnel. This article describes a proposed strategy for diagnosis and treatment of diabetic foot ulcers, based on experiences with infection and control strategies during the COVID-19 pandemic in China.


title: Improvement of the specificity of a pan‐viral microarray by using genus‐specific oligonucleotides and reduction of interference by host genomes

text: Rapid detection of viral pathogens is crucial for antiviral therapy. High‐density 60–70‐mer oligonucleotide microarrays have been explored for broad detection of many viruses. However, relatively low specificity and the complex analytical processes are the major limitations when pan‐viral oligonucleotide microarrays are used to detect viral pathogens. In this study, genus‐specific oligonucleotides were used as probes and modified sample preparations were carried out to improve the specificity and accuracy of the pan‐viral oligonucleotide microarray. Genus‐specific 63‐mer oligonucleotide probes were used for screening human pathogenic RNA viruses. A total of 628 oligonucleotide probes covering 32 RNA viral genera from 14 viral families were used. The number of oligonucleotide probes was decreased to simplify the analytical process of hybridization and to minimize cross‐hybridization. Host genomes were removed by DNase I/RNase T1 digestion before viral nucleic acid extraction, and non‐ribosomal hexanucleotides were used for reverse transcription to minimize interference of host genomes. Cultured viruses were used for microarray validation. The microarray was validated by cultured isolates that belonged to five viral genera. By using DNase I/RNase T1 digestion before viral nucleic acid extraction and non‐ribosomal hexanucleotides for reverse transcription, the specificity of the microarray was improved. Furthermore, the analytical process of hybridization results was simplified. The specificity of pan‐viral microarray could be improved by using genus‐specific oligonucleotides as probes and by using non‐ribosomal hexanucleotides for reverse transcription. Combined with subsequent degenerate reverse transcriptase‐polymerase chain reaction and sequencing processes, this improved genus‐specific oligonucleotides microarray provides a relatively flexible strategy for diagnosis of RNA virus diseases. J. Med. Virol. 83:1624–1630, 2011. © 2011 Wiley‐Liss, Inc.


title: Improving emergency preparedness capability of rural public health personnel in China

text: Summary Objectives Since the outbreaks of severe acute respiratory syndrome and avian influenza, improving the emergency preparedness capability of rural public health personnel has become a new priority in building the infrastructure needed to address public health emergencies. The Chinese Government has carried out a series of emergency preparedness education and training programmes to improve the emergency preparedness capability of rural public health personnel nationwide. The purpose of this study was to evaluate and develop a participatory emergency preparedness training programme for rural public health personnel. Study design The research emphasizes the major components of instructional design, including assessing, designing, delivering and evaluating training. The approach is an integrated system with results from one phase influencing the next, so that a series of steps are followed when developing, implementing and evaluating emergency preparedness training. Methods The 226 participants were rural public health personnel from 84 different rural centres for disease control and prevention in China. The programme was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-months after training (follow-up). Results The emergency preparedness training resulted in positive shifts in knowledge and skills for rural public health personnel. At follow-up, the knowledge and skill scores of participants declined slightly compared with the post-test levels (P >0.05). However, there was a significant increase compared with the pre-test levels (P <0.01). Moreover, more than 90% of participants reported that this training provided a valuable learning experience and reinforced the importance of emergency preparedness. Conclusions The emergency preparedness training programme was effective and feasible in improving the performance of rural public health personnel on emergency response. Further studies are needed to test the efficacy of the training approach for competency improvement.


title: Early SARS-CoV-2 outbreak detection by sewage-based epidemiology

text: Abstract Sewage can be used to determine the scale of COVID-19 outbreak. Sewage Epidemiology or Waste Based Epidemiology (WBE) approach has been successfully used to track and provide early warnings of outbreaks of pathogenic viruses such as Hepatitis A, Poliovirus and Norovirus. In untreated wastewater COVID-19 (excreted via faeces then introduced to wastewater) can survive from hours to days. Detection of COVID-19 can be carried out with nucleic acid−based polymerase chain reaction (PCR) assay, used for confirmation of COVID-19 patients around the globe. New cheaper and faster monitoring tools are being developed to detect Covid-19 in wastewater by biosensors, ELISA, or paper-based indicator methods. This will allow to reveal true scale of Covid-19 outbreak associated with population link to a specific wastewater treatment plant.


title: Synthesis of virus-specific RNA in permeabilized murine coronavirus-infected cells

text: Abstract We have developed a permeabilized cell system for assaying mouse hepatitis virus-specific RNA polymerase activity. This activity was characterized as to its requirements for mono- and divalent cations, requirements for an exogenous energy source, and pH optimum. This system faithfully reflects MHV-specific RNA synthesis in the intact cell, with regard to both its time of appearance during the course of infection and the products synthesized. The system is efficient and the RNA products were identical to those observed in intact MHV-infected cells as judged by agarose gel electrophoresis and hybridization. Permeabilized cells appear to be an ideal system for studying coronavirus RNA synthesis since they closely mimic in vivo conditions while allowing much of the experimental flexibility of truly cell-free systems.


title: Antenatal corticosteroid therapy and COVID‐19: Pathophysiological considerations

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many challenges in healthcare, including obstetrics. Therefore, we read with great interest the special editorial published in the AOGS regarding clinical recommendations for the management of coronavirus disease 2019 (COVID-19) in pregnant women.1 As illustrated by the authors, the usefulness and safety of corticosteroids as an adjuvant therapy for COVID-19 pneumonia remains controversial. Corticosteroids may diminish the inflammatory response, a major factor for lung damage and acute respiratory distress syndrome in viral respiratory tract infection. However, previous studies on corticosteroid therapy in severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus illustrated delayed viral clearance, with no survival benefit and perhaps even adverse outcomes.2 Some patients with COVID-19 exhibit biphasic disease evolution with a mild presentation followed by a secondary respiratory deterioration due to a cytokine storm, despite decreasing viral load.2 Therefore, timing of corticosteroid therapy might be particularly consequential, with early administration reducing inflammatory response and viral clearance during the initial phase.


title: Health Behavior Education, e-research and a (H1N1) Influenza (Swine Flu): Bridging the Gap between Intentions and Health Behavior Change

text: Abstract This study examined relations between risk perception/self-efficacy and handwashing intentions/behaviors during the A (H1N1) pandemic influenza. Data were collected from a longitudinal sample of Costa Ricans (NT1/T2 = 449/97). Results revealed that males and females presented a different social cognitive pattern in reaction to A (H1N1) pandemic. In females, the effects of risk perception/self-efficacy on handwashing behaviors were fully mediated by handwashing intentions. In males, self-efficacy influenced both directly and indirectly on handwashing behaviors, and risk perceptions showed no significant effect on handwashing behaviors. These results suggest that gender oriented protocols should be adopted by public health authorities in order to educate males and females in preventing both A (H1N1) and seasonal influenza.


title: Effect of tunicamycin and monensin on biosynthesis, transport, and maturation of bovine herpesvirus type-1 glycoproteins

text: Abstract The effect of tunicamycin and monensin on the biosynthesis, intracellular transport, and maturation of bovine herpesvirus type-1 (BHV-1) glycoproteins was examined. Tunicamycin completely inhibited the production of infectious virus particles and significantly reduced the incorporation of [3H]glucosamine into viral glycoproteins. In the presence of monensin, reduced amounts of infectious virus particles were produced, which was mainly due to inhibition of virus release, rather than virus production. Monensin only slightly inhibited viral glycoprotein synthesis. The effects of these compounds on infectivity indicated that glycosylation is required for the production of infectious virus, though complete processing of the glycoproteins is not essential. In addition, egress of the virions from infected cells probably requires a functional Golgi complex. In the presence of tunicamycin or monensin various degrees of glycosylation of the major glycoproteins occurred, consequently their rates of migration differed from that of the normal glycoproteins. Tunicamycin completely blocked glycosylation of GVP 6/11a/16 and GVP 7. In contrast, GVP 3/9 and GVP 11b were partially glycosyaated in the presence of tunicamycin. These results indicated that GVP 6/11a/16 and GVP 7 are N-linked glycoproteins, but GVP 3/9 and GVP 11b contain both N- and O-linked oligosaccharide side chains. Tunicamycin blocked the transport of all viral glycoproteins to the cell surface, suggesting that glycosylation is required for this process. In the presence of monensin, the viral glycoproteins were transported and expressed on the cell surface indicating that transport does not require complete processing of the glycoproteins and may occur via a Golgi-independent pathway. In addition, monensin-treated BHV-1 infected cells could act as target cells in an antibody-dependent cell cytotoxicity assay. Thus, complete glycosylation may not be essential for maintenance of antigenicity and participation in immune destruction.


title: Use of the Endoscopic Healing Index (EHI) for Monitoring of Disease Activity in Crohn’s Disease Patients in the COVID Era

text: Management of Crohn’s disease (CD) during COVID-19 is challenging when colonoscopy is not feasible. This study describes a blood-based test that has been validated against colonoscopy in CD patients as an alternative even in patients with high inflammation from infections.


title: Microbiology of hospital wastewater

text: The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. This chapter investigates the potential microbes such as bacteria, viruses, fungi, and parasites present in HWW along with the diseases associated and methods of treatment used. Due to the indiscriminate release of antibiotics from hospitals, HWW serves as a hotspot for emergence of antibiotic-resistance genes (ARGs) and antibiotic-resistance bacteria. This chapter discusses the ARGs occurrence in HWW, their prevalence in the environment, the molecular tools used for identification, and different mechanisms of horizontal gene transfer. Thus better understanding of the microbiology of HWW could further help in development of advanced treatment technologies for effective removal of microbes and their bioproducts (toxins and infectious nucleic acid) from HWW and contaminated water.


title: Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms

text: Abstract SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.


title: The sensitivity and specificity analyses of ambient temperature and population size on the transmission rate of the novel coronavirus (COVID-19) in different provinces of Iran

text: Abstract On 10 April 2020, Iran reported 68,192 COVID-19 cumulative cases including 4232 death and 35,465 recovery cases. Numerous factors could influence the transmission rate and survival of coronavirus. On this basis and according to the latest epidemiological researches, both ambient temperature (AT) and population size (PS) can be considered as significant transmissibility factors for coronavirus. The analysis of receiver operating characteristics (ROC) allows measuring the performance of a classification model using the confusion matrix. This study intends to investigate the sensitivity of AT and PS on the transmission rate of the novel coronavirus in different provinces of Iran. For this purpose, the information of each province of Iran including the annual average of AT and the number of healthy and diseased cases are categorized. Subsequently, the sensitivity and specificity analyses of both AT and PS factors are performed. The obtained results confirm that AT and PS have low sensibility and high sensitivity, respectively. Thus, there is no scientific reason to confirm that the number of COVID-19 cases in warmer climates is less than that of moderate or cold climates. Therefore, it is recommended that the cities/provinces with a population of over 1.7 million people have stricter inspections and more precise controls as their management policy.


title: MERS-CoV vaccine candidates in development: The current landscape

text: Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry.


title: Sequence analysis of infectious pancreatic necrosis virus genome segment B and its encoded VP1 protein: A putative RNA-dependent RNA polymerase lacking the Gly-Asp-Asp motif

text: Abstract The genome segment B sequence of infectious pancreatic necrosis virus was determined for both the Jasper and Sp serotypes. The sequences are 2784 and 2630 by long, respectively, and contain a single large open reading frame encoding the VP1 protein, the putative RNA-dependent RNA polymerase (RdRp) of IPNV. The proteins exhibit an 88% homology with each other, but only 41% with infectious bursal disease virus (IBDV) VP1, another member of the Birnaviridae. Despite the low overall homology between the IPNV and IBDV VP1 proteins, homologous regions were detected within the central portion of the proteins. The carboxy-proximal regions of the VP1, which contain very low amino acid homology, displayed evidence of conservation in structural features such as a hydrophilic, highly basic domain. Consensus sequences associated with GTP-binding proteins and RdRps were also detected in VP1. However, unlike the RdRps associated with single-stranded plus RNA viruses, the birnavirus RdRp lacks the Gly-Asp-Asp motif characteristic of this enzyme family.