title: Practice and technique of using face mask amongst adults in the community: a cross-sectional descriptive study

text: BACKGROUND: The proper use of face mask comprises the correct practice and wearing technique and is important in preventing the spread of respiratory infections. Previous studies have addressed only the aspect of practice and failed to provide a detailed account of face mask usage amongst community-based populations. This study examined the practice and technique of using face mask amongst adults. METHODS: A cross-sectional descriptive design was adopted. A quota sample of 1500 adults was recruited in Hong Kong during a nonepidemic state between January and February 2017. The participants’ practice of using face mask in five given situations was assessed using a questionnaire. Their technique in using face mask, including 12 steps, was assessed using an observation checklist. Statistical tests were used to compare the differences in practice and technique amongst adults of different gender and age groups. RESULTS: Findings revealed that the performance of the participants in both categories was unsatisfactory. In terms of practice, less than one-fifth of the participants reported that they always wore face mask when taking care of family members with fever (14.7%) or respiratory infections (19.5%). Male adults and those aged 55–64 reported low frequency in using face mask during required situations. In terms of technique, none of the participants performed all the required steps in using face mask correctly. More than 90% of the participants did not perform hand hygiene before putting on (91.5%), taking off (97.3%), or after disposing (91.5%) face mask. Adults aged 55 and above performed poorer than adults in the younger age groups. CONCLUSION: Compared with previous findings obtained during an epidemic, the performance of the participants during a nonepidemic state was less satisfactory. The possibility of developing fatigue after exposure to repeated epidemics was discussed. This study contributes to a comprehensive understanding of the use of face mask in a community and reveals the underperformed areas. Effort is required to enhance the proper practice of using face mask, convey the message that hand hygiene is an essential step in wearing and taking off a face mask and increase the public’s general concern in the value of using face mask.


title: Respiratory syncytial virus–associated illness in adults with advanced chronic obstructive pulmonary disease and/or congestive heart failure

text: BACKGROUND: Respiratory syncytial virus (RSV) is recognized as a serious pathogen in people with chronic cardiopulmonary conditions. Immunoprophylaxis might be considered for adults at high‐risk for frequent and severe RSV infection. Thus, we studied the incidence of RSV‐related medically attended acute respiratory illness (MARI) in adults with severe chronic obstructive pulmonary disease (COPD) and/or congestive heart failure (CHF). METHODS: Subjects ≥50 years of age with Gold Class III/IV COPD and/or American Heart Association class III/IV CHF and exposure to children ≥once per month were recruited. Subjects were evaluated over 1.5 to 2.5 years for RSV‐associated MARI, defined as polymerase chain reaction (PCR) and/or seroresponse. RESULTS: Four hundred forty‐five subjects were enrolled between October 2011 and May 2012. Overall, 99 RSV infections were documented by PCR or serology for a cumulative incidence of 22.2%. Of these, 42 (9.4%) subjects had protocol‐specified RSV‐MARI for an incidence of 4.68/100 patient‐seasons. All‐cause MARI was common (63.85/100 patient‐seasons) with rhinovirus most commonly identified. CONCLUSION: RSV infection was common in adults with severe COPD and/or advanced CHF. Given the severity of underlying cardiopulmonary diseases in the study population, most illnesses were surprisingly mild. Thus, active immunization rather than passive immunoprophylaxis with monoclonal antibodies may be a more cost‐effective strategy.


title: COVID-19 in an international European liver transplant recipient cohort

text: OBJECTIVE: Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. DESIGN: We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. RESULTS: 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57–70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. CONCLUSION: In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.


title: Subversion of Cellular Autophagosomal Machinery by RNA Viruses

text: Infection of human cells with poliovirus induces the proliferation of double-membraned cytoplasmic vesicles whose surfaces are used as the sites of viral RNA replication and whose origin is unknown. Here, we show that several hallmarks of cellular autophagosomes can be identified in poliovirus-induced vesicles, including colocalization of LAMP1 and LC3, the human homolog of Saccharomyces cerevisiae Atg8p, and staining with the fluorophore monodansylcadaverine followed by fixation. Colocalization of LC3 and LAMP1 was observed early in the poliovirus replicative cycle, in cells infected with rhinoviruses 2 and 14, and in cells that express poliovirus proteins 2BC and 3A, known to be sufficient to induce double-membraned vesicles. Stimulation of autophagy increased poliovirus yield, and inhibition of the autophagosomal pathway by 3-methyladenine or by RNA interference against mRNAs that encode two different proteins known to be required for autophagy decreased poliovirus yield. We propose that, for poliovirus and rhinovirus, components of the cellular machinery of autophagosome formation are subverted to promote viral replication. Although autophagy can serve in the innate immune response to microorganisms, our findings are inconsistent with a role for the induced autophagosome-like structures in clearance of poliovirus. Instead, we argue that these double-membraned structures provide membranous supports for viral RNA replication complexes, possibly enabling the nonlytic release of cytoplasmic contents, including progeny virions, from infected cells.


title: Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections

text: OBJECTIVES: The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. METHODS: Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. RESULTS: Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. CONCLUSION: Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. SUMMARY: We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms.


title: The Gendered Religious Response to State Action on the Coronavirus Pandemic

text: State action to curtail the spread of the coronavirus has meant advising, and sometimes mandating, houses of worship to close to in-person worship. While mostly cooperative, the religious response has been varied and has exposed a hardened, defiant core. Informed by gendered religious worldviews, religious defiance is led by men and disproportionately supported by men. In this article, we document the extent of the defiance as of late March 2020 with our survey data and then investigate how gendered religious worldviews serve to track men to public roles and women to private ones. We attempt to confirm the nature of these effects with a gendered nationalism item and parallel gender gaps in political participation.


title: Correlation between Preventive Health Behaviors and Psycho-Social Health Based on the Leisure Activities of South Koreans in the COVID-19 Crisis

text: COVID-19 has caused unprecedented damage worldwide, and quarantine and lockdown measures have been undertaken globally. This study focused on the differences in preventive behaviors and psycho-social health of South Koreans, as people continue engaging in leisure activities under self-regulation without a lockdown measure imposed by the government. For the sample, the frame of the “2018 Population and Housing Census” in South Korea was applied, and data from 1770 people were analyzed. The results showed that the groups participating in culture and arts and social activities displayed characteristics with high prevention. Additionally, the groups that continued leisure activities for more than five years and with family showed high preventive behaviors. Meanwhile, participation in leisure activities with friends of the opposite sex lowered preventive behavior. In terms of psycho-social health, all groups were affiliated to the potential stress group and there were no differences in the period and participation time for leisure activities. Furthermore, the group participating in leisure activities with their school and group experienced psychological stability. When lockdown measures are eased, the aforementioned characteristics should be considered to design government policy; they can also be used as a reference for public health in case of a future outbreak of an epidemic.


title: Severe acute respiratory syndrome‐related diarrhea

text: Background: Severe acute respiratory syndrome (SARS) is an emerging infectious disease and diarrhea has been reported in up to 76% of cases. The purpose of the present paper was to carry out a retrospective study of the clinical and demographic data of SARS patients with diarrhea in Princess Margaret Hospital. Methods: From 1 to 31 March 2003, hospital records from 240 patients with confirmed SARS were studied. Patients with watery stool of ≥3 times/day for at least 3 consecutive days were defined as the diarrhea group. Clinical and demographic data were compared between the diarrhea and non‐diarrhea groups. Chest X‐ray (CXR) scores during the peak of diarrhea period were recorded by a respiratory physician. These CXR scores were correlated with the peak frequency of diarrhea by Spearman's correlation coefficient. Results: Diarrhea occurred in 20.4% of patients after admission. Female patients were predominant with a female to male ratio of 6:1 (P < 0.001) and 69.4% of patients were living in Amoy Gardens Estate (P = 0.01). The proportions of patients requiring ventilatory care and mortality in the diarrhea group were 8.2% and 2%, respectively, which were significantly lower than those in the non‐diarrhea group (27.6% and 16.2%, P < 0.005). The CXR scores during the peak of diarrhea were not correlated with the maximum frequency of diarrhea (r = −0.09, P = 0.5). Conclusions: A total of 20.4% of SARS patients had the complication of diarrhea after hospital admission. Both female sex and being a resident of Amoy Gardens Estate were associated with diarrhea. The diarrhea group had a better prognosis.


title: Infectious diarrhea: Pathogenesis and risk factors

text: Abstract Our understanding of the pathogenesis of infectious, especially bacterial, diarrhea has increased dramatically. New etiologic agents, mechanisms, and diseases have become known. For example, Escherichia coli serogroup 0157 is now known to cause acute hemorrhagic colitis. Also, E. coli serogroups that produce Shiga toxin are recognized as etiologic agents in the hemolytic-uremic syndrome. The production of bacterial diarrhea has two major facets, bacterial-mucosal interaction and the induction of intestinal fluid loss by enterotoxins. Bacterial-mucosal interaction can be described in stages: (1) adherence to epithelial cell microvilli, which is often promoted by or associated with pill; (2) close adherence (enteroadherence), usually by classic enteropathogenic E. coli, to mucosal epithelial cells lacking microvilli; and (3) mucosal invasion, as with Shigella and Salmonella infections. Further large strides in understanding infectious diarrhea are likely with the cloning of virulence genes if additional host-specific animal pathogens become available for study.


title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.

text: BACKGROUND: Coccidiosis due to Eimeria spp. infections in lambs causes increased mortality and substantial production losses, and anticoccidials are important for control of the infection. Anticoccidial resistance has been reported in poultry and swine, and we recently described reduced toltrazuril efficacy in ovine Eimeria spp. in some Norwegian sheep farms using a newly developed faecal oocyst count reduction test (FOCRT). The aim of the present study was to use a controlled efficacy trial to assess the efficacy of toltrazuril against a field isolate suspected of being resistant. METHODS: Twenty lambs, 17–22 days old and raised protected against exposure to coccidia, were infected with a field isolate of 100,000 Eimeria spp. oocysts. This isolate was obtained from a farm with a previously calculated drug efficacy of 56% (95% confidence interval: -433.9 to 96.6%). At day 7 post-infection, 10 of the lambs were orally treated with 20 mg/kg toltrazuril (Baycox Sheep vet., Bayer Animal Health), while the other 10 lambs (controls) were given physiological saline. Clinical examinations were conducted, and weight gains recorded. Daily faecal samples were scored for diarrhoea on a scale from 1 to 5, and oocyst excretion was determined using a modified McMaster technique. Oocysts were morphologically identified to species level. At 17–24 days post-infection, the lambs were euthanized and necropsied. RESULTS: The tested Eimeria isolate was resistant against toltrazuril, and resistance was seen in both pathogenic and non-pathogenic species. In addition, no significant differences in faecal score, growth, gross pathology or histological changes were identified between the two groups. The pathogenic E. ovinoidalis was the dominant species, and no significant difference in the individual prevalence of E. ovinoidalis post-treatment was found between treated (66.9%) and control lambs (61.9%). Other species identified included E. crandallis/weybridgensis, E. parva, E. marsica, E. faurei, E. pallida, E. ahsata and E. bakuensis. CONCLUSIONS: This study confirms toltrazuril resistance in ovine Eimeria spp.; in addition, the data support the use of FOCRT as an appropriate tool for field evaluation of anticoccidial efficacy. Due to limited anticoccidial treatment alternatives, these findings may have important implications for the sheep industry, particularly in northern Europe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2976-4) contains supplementary material, which is available to authorized users.


title: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study

text: BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.


title: Pandemia De La Covid-19 Y Salud Mental: Reflexiones Iniciales Desde La Atención Primaria De Salud Española

text: Resumen En el trabajo se hace una aproximación a las características psicológicas y psicosociales que está adquiriendo la Pandemia de la Covid-19 en los países de nuestro medio socio-cultural. Se discute la escasez de investigaciones al respecto y la necesaria aceptación de la incertidumbre para enfrentar la situación, tanto a nivel social, como sanitario y personal. En consecuencia, se proponen una serie de reflexiones y recomendaciones para los cuidados psicológicos de la población, los trabajadores sanitarios y la organización social basándose en 1) La existencia de investigaciones psicológicas y psicosociales sobre temas conectados con estos. 2) En las nuevas perspectivas neurocientíficas sobre las emociones y su elaboración en situaciones de crisis. Summary An approach is made to the psychological and psychosocial characteristics that the Covid-19 Pandemic is acquiring in the countries of our socio-cultural environment. The scarcity of research in this regard and the necessary acceptance of uncertainty to face the situation, both socially, as well as health and psychological, are discussed. Consequently, a series of reflections and recommendations are proposed for the psychological care of the population, health workers and social organization based on: 1) The existence of psychological and psychosocial research into connected fields. 2) In the new neuroscientific perspectives on emotions and their elaboration in crisis situations.


title: Aconitate hydratase of mammals under oxidative stress

text: Data on the structure, functions, regulation of activity, and expression of cytosolic and mitochondrial aconitate hydratase isoenzymes of mammals are reviewed. The role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron is described. Information on modifications of the aconitate hydratase molecule and changes in expression under oxidative stress is generalized. The role of aconitate hydratase in the pathogenesis of some diseases is considered.


title: Serum Proteomic Fingerprints of Adult Patients with Severe Acute Respiratory Syndrome

text: Background: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease. Methods: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry. Results: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733–0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c α chain (m/z 28 119) and an internal fragment of fibrinogen α-E chain (m/z 5908). Immunoglobulin κ light chain (m/z 24 505) positively correlated with viral load. Conclusions: Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.


title: The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP‐E, SIOP‐PODC, IPSO, PROS, CCI, and St Jude Global

text: The COVID‐19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS‐CoV‐2 (COVID‐19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low‐ and middle‐income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP‐PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.


title: Chapter 33 Blood, Blood Components, Plasma, and Plasma Products

text: Abstract This review of the 2013–2014 publications on important side effects of blood, blood components, plasma, and plasma products covers albumin, blood transfusion (erythrocytes, granulocytes, and platelets), blood substitutes (hemoglobin-based oxygen carriers), plasma products (alpha1-antitrypsin, C1 esterase inhibitor concentrate, cryoprecipitate, and fresh frozen plasma), plasma substitutes (dextrans, etherified starches, and gelatin), globulins (intravenous immunoglobulin, subcutaneous immunoglobulin, and Anti-D immunoglobulin), coagulation proteins (factor I, factor II, factor VIIa, factor VIII, factor IX, prothrombin complex concentrate, and von Willebrand factor/factor VIII concentrates), erythropoietin and derivatives, thrombopoietin and receptor agonists, transmission of infectious agents through blood donation, and stem cells. This chapter includes blood products for which hemovigilance is in force, and allows the reader to stay up to date on newly recognized and published data in the blood product arena. Since blood and plasma products are available through blood donation, prevention of transmitted infections is of extreme importance and is also discussed here.


title: Oral ulceration and blistering in patients with COVID-19

text: Design Case series. Introduction The most common signs and symptoms of SARS-CoV-2 infection include headache, sore throat, hyposmia, hypogeusia, diarrhoea, dyspnoea and pneumonia. Dermatological manifestations have also been reported but few authors have documented oral signs and symptoms. Methods Three cases are reported where oral ulceration or blistering is found in patients with confirmed or suspected COVID-19. Results One patient had serologically confirmed COVID-19, whilst the remaining two cases were only suspected. Two patients reported pain from the palate, whilst the third reported in the tongue. The first two patients had lesions affecting keratinised tissue consistent with herpes simplex lesions but with no history of herpetic infection. The third patient had lesions compatible with erythema multiforme. Conclusions The authors suggest a link between COVID-19 and oral ulceration and blistering, but acknowledge these signs may often go undetected due to a lack of intraoral examination during hospital admission.


title: On the evolutionary epidemiology of SARS-CoV-2

text: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.


title: A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19

text: Hydroxychloroquine, an essential treatment for many patients with rheumatologic conditions, has recently garnered widespread attention as a potential treatment for COVID-19 infection. The authors appraise the study generating this interest and highlight the potential consequences of rapid dissemination of overinterpreted data, particularly for people with conditions for which hydroxychloroquine has demonstrated benefits in preventing organ damage and life-threatening disease flares.


title: Audit and feedback to improve laboratory test and transfusion ordering in critical care: a systematic review

text: BACKGROUND: Laboratory tests and transfusions are sometimes ordered inappropriately, particularly in the critical care setting, which sees frequent use of both. Audit and Feedback (A&F) is a potentially useful intervention for modifying healthcare provider behaviors, but its application to the complex, team-based environment of critical care is not well understood. We conducted a systematic review of the literature on A&F interventions for improving test or transfusion ordering in the critical care setting. METHODS: Five databases, two registries, and the bibliographies of relevant articles were searched. We included critical care studies that assessed the use of A&F targeting healthcare provider behaviors, alone or in combination with other interventions to improve test and transfusion ordering, as compared to historical practice, no intervention, or another healthcare behaviour change intervention. Studies were included only if they reported laboratory test or transfusion orders, or the appropriateness of orders, as outcomes. There were no restrictions based on study design, date of publication, or follow-up time. Intervention characteristics and absolute differences in outcomes were summarized. The quality of individual studies was assessed using a modified version of the Effective Practice and Organisation of Care Cochrane Review Group’s criteria. RESULTS: We identified 16 studies, including 13 uncontrolled before-after studies, one randomized controlled trial, one controlled before-after study, and one controlled clinical trial (quasi-experimental). These studies described 17 interventions, mostly (88%) multifaceted interventions with an A&F component. Feedback was most often provided in a written format only (41%), more than once (53%), and most often only provided data aggregated to the group-level (41%). Most studies saw a change in the hypothesized direction, but not all studies provided statistical analyses to formally test improvement. Overall study quality was low, with studies often lacking a concurrent control group. CONCLUSIONS: Our review summarizes characteristics of A&F interventions implemented in the critical care context, points to some mechanisms by which A&F might be made more effective in this setting, and provides an overview of how the appropriateness of orders was reported. Our findings suggest that A&F can be effective in the context of critical care; however, further research is required to characterize approaches that optimize the effectiveness in this setting alongside more rigorous evaluation methods. TRIAL REGISTRATION: PROSPERO CRD42016051941.


title: Chapter Fourteen Evaluating enzyme activities and structures of DUBs

text: Abstract Ubiquitin signaling requires tight control of all aspects of protein ubiquitination, including the timing, locale, extent, and type of modification. Dysregulation of any of these signaling features can lead to severe human disease. One key mode of regulation is through the controlled removal of the ubiquitin signal by dedicated families of proteases, termed deubiquitinases. In light of their key roles in signal regulation, deubiquitinases have become a recent focus for therapeutic intervention as a means to regulate protein abundance. This work and recent discoveries of novel deubiquitinases in humans, viruses, and bacteria, provide the impetus for this chapter on methods for evaluating the activities and structures of deubiquitinases. An array of available deubiquitinase substrates for biochemical characterization are presented and their limitations as standalone tools are discussed. Methods for the determination and analysis of deubiquitinase structure are also presented, with a focus on visualizing recognition of the ubiquitin substrate.


title: The COVID-19 pandemic: a new challenge for syndromic surveillance

text: The COVID-19 pandemic is exerting major pressures on society, health and social care services and science. Understanding the progression and current impact of the pandemic is fundamental to planning, management and mitigation of future impact on the population. Surveillance is the core function of any public health system, and a multi-component surveillance system for COVID-19 is essential to understand the burden across the different strata of any health system and the population. Many countries and public health bodies utilise ‘syndromic surveillance’ (using real-time, often non-specific symptom/preliminary diagnosis information collected during routine healthcare provision) to supplement public health surveillance programmes. The current COVID-19 pandemic has revealed a series of unprecedented challenges to syndromic surveillance including: the impact of media reporting during early stages of the pandemic; changes in healthcare-seeking behaviour resulting from government guidance on social distancing and accessing healthcare services; and changes in clinical coding and patient management systems. These have impacted on the presentation of syndromic outputs, with changes in denominators creating challenges for the interpretation of surveillance data. Monitoring changes in healthcare utilisation is key to interpreting COVID-19 surveillance data, which can then be used to better understand the impact of the pandemic on the population. Syndromic surveillance systems have had to adapt to encompass these changes, whilst also innovating by taking opportunities to work with data providers to establish new data feeds and develop new COVID-19 indicators. These developments are supporting the current public health response to COVID-19, and will also be instrumental in the continued and future fight against the disease.


title: Using transgenic plants and modified plant viruses for the development of treatments for human diseases

text: Production of proteins in plants for human health applications has become an attractive strategy attributed by their potentials for low-cost production, increased safety due to the lack of human or animal pathogens, scalability and ability to produce complex proteins. A major milestone for plant-based protein production for use in human health was achieved when Protalix BioTherapeutics produced taliglucerase alfa (Elelyso®) in suspension cultures of a transgenic carrot cell line for the treatment of patients with Gaucher's disease, was approved by the USA Food and Drug Administration in 2012. In this review, we are highlighting various approaches for plant-based production of proteins and recent progress in the development of plant-made therapeutics and biologics for the prevention and treatment of human diseases.


title: Inflammatory Bowel Disease Care in the COVID-19 Pandemic Era: The Humanitas, Milan, Experience

text: The outbreak of the COVID-19 caused by coronavirus SARS-CoV2, is rapidly spreading worldwide. This is the first pandemic caused by a coronavirus in history. More than 150 000 confirmed cases worldwide are reported involving the SARS-CoV2, with more than 5000 COVID-19-related deaths on March 14, 2020. Fever, chills, cough, shortness of breath, generalised myalgia, malaise, drowsiness, diarrhoea, confusion, dyspnoea, and bilateral interstitial pneumonia are the common symptoms. No therapies are available, and the only way to contain the virus spread is to regularly and thoroughly clean one’s hands with an alcohol-based hand rub or wash them with soap and water, to maintain at least 1 m [3 feet] distance from anyone who is coughing or sneezing, to avoid touching eyes, nose, and mouth, and to stay home if one feels unwell. No data are available on the risk of COVID-19 and outcomes in inflammatory bowel disease [IBD] patients. Outbreak restrictions can impact on the IBD care. We aim to give a viewpoint on how operationally to manage IBD patients and ensure quality of care in the current pandemic era.


title: Ultraviolet Light (UV) Inactivation of Porcine Parvovirus in Liquid Plasma and Effect of UV Irradiated Spray Dried Porcine Plasma on Performance of Weaned Pigs

text: A novel ultraviolet light irradiation (UV-C, 254 nm) process was designed as an additional safety feature for manufacturing of spray dried porcine plasma (SDPP). In Exp. 1, three 10-L batches of bovine plasma were inoculated with 10(5.2±0.12) tissue culture infectious dose 50 (TCID(50)) of porcine parvovirus (PPV) per mL of plasma and subjected to UV-C ranging from 0 to 9180 J/L. No viable PPV was detected in bovine plasma by micro-titer assay in SK6 cell culture after UV-C at 2295 J/L. In Exp. 2, porcine plasma was subjected to UV-C (3672 J/L), then spray dried and mixed in complete mash diets. Diets were a control without SDPP (Control), UV-C SDPP either at 3% (UVSDPP3) or 6% (UVSDPP6) and non-UV-C SDPP at 3% (SDPP3) or 6% (SDPP6). Diets were fed ad libitum to 320 weaned pigs (26 d of age; 16 pens/diet; 4 pigs/pen) for 14 d after weaning and a common diet was fed d 15 to 28. During d 0 to 14, pigs fed UVSDPP3, UVSDPP6, or SDPP6 had higher (P < 0.05) weight gain and feed intake than control. During d 0 to 28, pigs fed UVSDPP3 and UVSDPP6 had higher (P < 0.05) weight gain and feed intake than control and SDPP3, and SDPP6 had higher (P < 0.05) feed intake than control. Also, pigs fed UVSDPP had higher (P < 0.05) weight gain than pigs fed SDPP. In conclusion, UV-C inactivated PPV in liquid plasma and UVSDPP used in pig feed had no detrimental effects on pig performance.


title: Impact of viral multiplex real-time PCR on management of respiratory tract infection: a retrospective cohort study

text: BACKGROUND: Significance and clinical utility of multiple virus detection by multiplex real-time polymerase chain reaction (rtPCR) in respiratory tract infection remain unclear. METHODS: This retrospective cohort study analyzed how virus detection affected clinical management. During a 27-month period, clinical and laboratory information was collected from all children and adults in two Swiss tertiary centres whose respiratory samples were tested for respiratory viruses with a 16-plex rtPCR test. RESULTS: Pathogens were identified in 140 of 254 patients (55%); of those patients, there was ≥1 virus in 91 (65%), ≥ 1 bacterium in 53 (38%), and ≥1 virus and bacterium in 11 (8%). Of 80 patients with viral infection, 59 (74%) received antibiotics. Virus detection was associated with discontinuation of antibiotics in 2 of 20 adults (10%) and 6 of 14 children (43%). Overall 12 adults (34%) and 18 children (67%) were managed correctly without antibiotics after virus detection (p = 0.01). When taking biomarkers, radiologic presentations, and antibiotic pre-treatment into account, the impact of rtPCR and appropriateness of therapy for clinically viral infections increased to 100% in children and 62% in adults. CONCLUSIONS: A substantial reduction of unnecessary antibiotic prescriptions seems possible. Appropriate application of rtPCR results in respiratory tract infections should be encouraged.


title: Conjunctiva is not a preferred gateway of entry for SARS‐CoV‐2 to infect respiratory tract

text: The conjunctival mucosa is directly exposed to infectious droplets expelled by patients during close contact and fomites when the eye is touched by contaminated hands.(2, 3) More over, the mucosa of the conjunctiva and upper respiratory tract is connected by nasolacrimal duct, and share the same entry receptor of SARS‐CoV‐2, angiotensin‐converting enzyme 2 (ACE2), on host cell membranes.(2, 3) Hence, it is reasonable to postulate that the conjunctiva may be easily involved in SARS‐CoV‐2 infection, and may even act as a route of transmission during SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Aspartic acid at residue 185 modulates the capacity of HP-PRRSV nsp4 to antagonize IFN-I expression

text: Abstract In a previous study, we have shown that highly-pathogenic PRRSV (HP-PRRSV) nonstructural protein 4 (nsp4) antagonizes type I IFN expression induced by poly(I:C). Here, we demonstrated that the mutation of Aspartic acid 185 (Asp185) impaired the ability of nsp4 to inhibit IFN-I production induced by poly(I:C). Subsequently, we verified that all the mutants at the residue 185, regardless of amino acid size (including Cys and Ser) and charge (including Glu and Lys), impaired nsp4 catalytic activity. However, when Asp185 in nsp4 was replaced by a similar structure amino acid Asparagine 185 (Asn185), nsp4 stayed but with a decreased protease activity. Importantly, the recombinant virus with Asn185 mutation in HP-PRRSV-nsp4 exhibited slower replication rate and higher ability to induce IFN-I expression compared with wild-type (wt) HP-PRRSV.


title: Rethinking ‘essential’ and ‘nonessential’: the developmental paediatrician’s COVID-19 response

text: While terms such as ‘essential’ and ‘nonessential’ used amidst the COVID-19 pandemic may serve a practical purpose, they also pose a risk of obstructing our view of the harmful indirect health consequences of this crisis. SARS-CoV-2 cases and deaths in children are minimal compared to adults, but the pandemic impacts other ‘essential’ aspects of children’s health including child development and the associated areas of paediatric behaviour, mental health, and maltreatment. Alongside the management of severe SARS-CoV-2 cases in emergency rooms and intensive care units, continuing to care for children with developmental disabilities must also be concurrently championed as ‘essential’ during this crisis. The potentially devastating lifelong effects of the pandemic and isolation on an already vulnerable population demand that action be taken now. Video conferences and phone calls are ‘essential’ instruments we can use to continue to provide quality care for our patients.


title: Implicit Riesz wavelets based-method for solving singular fractional integro-differential equations with applications to hematopoietic stem cell modeling

text: Riesz wavelets in [Formula: see text] have been proven as a useful tool in the context of both pure and numerical analysis in many applications, due to their well prevailing and recognized theory and its natural properties such as sparsity and stability which lead to a well-conditioned scheme. In this paper, an effective and accurate technique based on Riesz wavelets is presented for solving weakly singular type of fractional order integro-differential equations with applications to solve system of fractional order model that describe the dynamics of uninfected, infected and free virus carried out by cytotoxic T lymphocytes (CTL). The Riesz wavelet in this work is constructed via the smoothed pseudo-splines refinable functions. The advantage of using such wavelets, in the context of fractional and integro-differential equations, lies on the simple structure of the reduced systems and in the powerfulness of obtaining approximated solutions for such equations that have weakly singular kernels. The proposed method shows a good performance and high accuracy orders.


title: Pulse Therapy With Corticosteroids and Intravenous Immunoglobulin in the Management of Severe Tocilizumab-Resistant COVID-19: A Report of Three Clinical Cases

text: We present the cases of three patients with severe, life-threatening coronavirus disease 2019 (COVID-19) who had failed to achieve substantial improvement on intial treatment. They subsequently received pulse therapy with methylprednisolone [1,000 mg/day intravenously (IV) for three consecutive days] and IV immunoglobulin (20 g/day). This treatment regimen was associated with a prompt resolution of respiratory failure, elimination of clinical manifestations of the cytokine release syndrome (CRS), and reversal of pulmonary CT changes. The treatment was generally safe and well-tolerated. There was no evidence of protracted persistence of the virus in the patients. Further randomized controlled trials are required to better understand the efficacy and safety of high-dose methylprednisolone and IV immunoglobulin, separately or in combination with each other, in the treatment of severe, life-threatening COVID-19.


title: Mental health groups providing support, education in wake of COVID‐19

text: As news and updates continue to spread regarding the new coronavirus (COVID‐19), the deadly virus that causes respiratory illness and pneumonia, mental health groups and organizations have issued information to consumers, providers and the mental health community at large about ways of addressing the virus and seeking information from public health sources.


title: Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients

text: This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.


title: Manejo farmacológico de pacientes con enfermedades hepáticas y pancreáticas que involucran terapias inmunosupresoras. Posicionamiento en el marco de la pandemia de SARS-COV-2 (COVID-19)

text: Resumen La enfermedad por coronavirus 2019 (COVID-19) es causada por el virus de Síndrome Respiratorio Agudo Grave - Coronavirus 2 (SARS-CoV-2). COVID 19 ha afectado cerca de 2 millones de personas en todo el mundo en menos de 4 meses posterior al reporte de los primeros casos en China en diciembre 2019. La relación que guarda la enfermedad por SARS-Cov-2 con el tratamiento inmunosupresor utilizado en diversos trastornos gastrointestinales es incierta, esto genera el debate sobre suspender el tratamiento inmunosupresor para mejorar el pronóstico de la infección, lo cual incluye el riesgo inherente de rechazo de injerto o agudización de enfermedades autoinmunes que potencialmente pudieran agravar el curso de la infección. En base a la evidencia disponible se logra establecer una postura de tratamiento en pacientes con enfermedades gastrointestinales que requieren terapia inmunosupresora. Abstract The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 affected close to 2 million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.


title: A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model

text: BACKGROUND: Infection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted. METHODS: We extended and optimized our previous recombinant adenovirus 5 (rAd5)–based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg(+)) mice. RESULTS: Immunization of hDPP4 Tg(+) mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1– but not rAd5-S1/F/CD40L–immunized mice exhibited marked pulmonary perivascular hemorrhage post–MERS-CoV challenge despite the observed protection. CONCLUSIONS: Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.


title: A multiplex real-time PCR assay for the detection and differentiation of five bovine pinkeye pathogens

text: Abstract Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is one of the most common eye diseases in cattle. Several pathogens have been associated with IBK cases, however, Moraxella bovis, Moraxella bovoculi, Mycoplasma bovis, Mycoplasma bovoculi and bovine herpesvirus type 1 (BHV-1) are most frequently observed. A multiplex real-time PCR assay using two reactions was developed for the detection and differentiation of these five pathogens. Detection sensitivities of the multiplex assays were compared to singleplex reactions testing for the same targets. Correlation coefficients (R2) of >0.99, and PCR efficiencies between 92 and 106% were demonstrated in all singleplex and multiplex real-time PCR reactions. The limits of detection (LOD) of multiplex assays for Moraxella bovis, Moraxella bovoculi, Mycoplasma bovis, Mycoplasma bovoculi and BHV-1 were 19, 23, 25, 24 and 26 copies per reaction, respectively. No cross amplification was observed for specificity testing of 179 IBK positive clinical samples and 55 non-target clinical samples. Percentage of clinical samples positive for Mycoplasma bovoculi, Moraxella bovoculi, Moraxella bovis, BHV-1 and Mycoplasma bovis were 88.8% (159/179), 75.9% (136/179), 60.3% (108/179), 11.7% (21/179) and 10.0% (18/179), respectively. Moraxella bovis, Moraxella bovoculi and Mycoplasma bovoculi were more prevalent than Mycoplasma bovis and BHV-1 in IBK samples collected from animals in this study population. Our data indicates that the multiplex real-time PCR panel assay is highly sensitive and highly specific for the detection and differentiation of the five major pathogens associated with bovine pinkeye.


Letter: Anosmia in COVID-19: Severe Acute Respiratory Syndrome Coronavirus 2 Through the Nasoliary Epithelium and a Possible Spreading Way to the Central Nervous System—A Purpose to Study


title: Discovery of Diverse Rodent and Bat Pestiviruses With Distinct Genomic and Phylogenetic Characteristics in Several Chinese Provinces

text: Bats and rodents are widely distributed worldwide and can be native or intermediate reservoirs of many important zoonotic viruses. Pestiviruses are a group of virus species of the genus Pestivirus under the family Flaviviridae that can infect a wide variety of artiodactylous hosts, including swine and ruminants. Two classic types of pestiviruses, bovine viral diarrhea virus and classical swine fever virus, are important causative agents of mild-to-severe disease in bovine and swine hosts, respectively, and cause tremendous economic losses in these industries. Recent reports revealed that bats and rodents could also act as natural hosts of pestiviruses and an atypical porcine pestivirus, which cause disease in piglets, showed a close genetic relationship with a specific bat pestivirus, RaPestV-1. This study aimed to describe the detection and characterization of novel pestiviruses from bats and rodents in different locations by analyzing the available bat and rodent virome data from throughout China. Two bat pestivirus species and four rodent pestivirus species that are distinct from other known viruses were identified and sequenced. These viruses were identified from two bat species and four rodent species in different Chinese provinces. There were two distinct lineages present in these viruses, that differ from artiodactylous pestivirus. These findings expand our understanding of the genetic diversity of pestiviruses in bats and rodents and suggest the presence of a diverse set of pestiviruses in non-artiodactylous hosts. This study may provide new insight for the prevention of future viral disease outbreaks originating from bats and rodents.


title: Exploitation of viral properties for intracellular delivery

text: Nanotechnology is an expanding area of study with potentially pivotal applications in a discipline as medicine where new biomedical active molecules or strategies are continuously developing. One of the principal drawbacks for the application of new therapies is the difficulty to cross membranes that represent the main physiological barrier in our body and in all living cells. Membranes are selectively permeable and allow the selective internalization of substances; generally, they form a highly impermeable barrier to most polar and charged molecules, and represent an obstacle for drug delivery, limiting absorption to specific routes and mechanisms. Viruses provide attracting suggestions for the development of targeted drug carriers as they have evolved naturally to deliver their genomes to host cells with high fidelity. A detailed understanding of virus structure and their mechanisms of entry into mammalian cells will facilitate the development and analysis of virus‐based materials for medical applications. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.


title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks?

text: ABSTRACT Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Could these drugs – which include angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) – be harmful or potential key therapeutic agents in COVID-19?


title: Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders

text: An association between many psychiatric and gluten-related disorders has been known for some time. In the case of schizophrenia and mood disorders, the major psychiatric disorders, there is much evidence, not without contradictions, of a possible association between schizophrenia and celiac disease. The association between mood disorders and gluten-related disorders, especially celiac disease, has only been studied for depression, often coupled with anxiety, and very recently for bipolar disorder. Since non-celiac gluten sensitivity is now known to be different from celiac disease, many studies have shown that gluten sensitivity is also associated with major psychiatric disorders. Here we review the literature on the association between schizophrenia/mood disorders and celiac disease/gluten sensitivity, pointing out the differences between these associations.


title: Chirurgie in der SARS-CoV-2-Pandemie: Empfehlungen zum operativen Vorgehen

text: BACKGROUND: In February 2020 Germany was also hit by the SARS-CoV‑2 pandemic. Even patients infected by SARS-CoV‑2 or COVID-19 may need operative procedures. Currently, no uniform recommendations exist on precautions to be taken when operating on these patients. Furthermore, they may differ from one hospital to another. METHODS: The task force COVID-19 of the emergency, intensive and severely injured section of the German Trauma Society (DGU e. V.) has developed consensus-based recommendations on surgical treatment of patients with SARS-CoV‑2 infections. Great importance is placed on the implementation in hospitals at all levels of care. RESULTS: The indications for surgical interventions in patients with COVID-19 infections require an extremely critical evaluation. When indicated these surgical intervention should ideally be performed in a separate operating theater. All personnel involved should wear personal protective equipment with FFP2 masks, face shields and double gloves. The emergency team in the resuscitation bay should generally wear the same personal protective equipment. Special training is mandatory and the exposure of team members should be minimized. CONCLUSION: The recommendations are principally used for all kinds of surgery and comply with the currently available knowledge. Nevertheless, all recommendations represent a compromise between maximum safety of all medical staff and practicability in the routine hospital workflow.


title: Individual variation in susceptibility or exposure to SARS-CoV-2 lowers the herd immunity threshold

text: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, the susceptible subpopulation is depleted causing the incidence of new cases to decline. Variation in individual susceptibility or exposure to infection exacerbates this effect. Individuals that are more susceptible or more exposed tend to be infected earlier, depleting the susceptible subpopulation of those who are at higher risk of infection. This selective depletion of susceptibles intensifies the deceleration in incidence. Eventually, susceptible numbers become low enough to prevent epidemic growth or, in other words, the herd immunity threshold (HIT) is reached. Although estimates vary, simple calculations suggest that herd immunity to SARS-CoV-2 requires 60-70% of the population to be immune. By fitting epidemiological models that allow for heterogeneity to SARS-CoV-2 outbreaks across the globe, we show that variation in susceptibility or exposure to infection reduces these estimates. Accurate measurements of heterogeneity are therefore of paramount importance in controlling the COVID-19 pandemic.


title: Modal share changes due to COVID-19: The case of Budapest

text: Abstract The COVID-19 pandemic has had a rapid and significant impact on mobility. One of the most important responses of countries worldwide to slow the spread of the pandemic has been to restrict the movement of people, which has had a considerable effect on transport systems. However, the reduction of transport is not identical for all modes of transport: public transport has seen the greatest decline by far. Understanding urban modal share developments during a pandemic situation can help cities better prepare for transport management in the future.


title: A Critical Juncture in Fiscal Federalism? Canada's Response to COVID-19

text: The COVID-19 crisis could trigger a critical juncture for several institutional arrangements in Canada, potentially leading to notable changes in fiscal federalism. This research note combines insights from historical institutionalism with recent economic and fiscal projections to explore avenues for reform in response to the COVID-19 crisis. Given the magnitude of the crisis, provincial governments may be unable to absorb the fiscal costs on their own. But vast differences in fiscal and economic circumstances across provinces make federal arrangements difficult to design. We argue that intergovernmental power dynamics and the principle of provincial autonomy are particularly important considerations in thinking about fiscal federalism post–COVID-19.


title: Chapter 2 Virus Structure and Classification

text: Abstract Viruses have several common characteristics: they are small, have DNA or RNA genomes, and are obligate intracellular parasites. The virus capsid functions to protect the nucleic acid from the environment, and some viruses surround their capsid with a membrane envelope. Most viruses have icosahedral or helical capsid structure, although a few have complex virion architecture. An icosahedron is a geometric shape with 20 sides, each composed of an equilateral triangle, and icosahedral viruses increase the number of structural units in each face to expand capsid size. The classification of viruses is very useful, and the International Committee on Taxonomy of Viruses is the official body that classifies viruses into order, family, genus, and species taxa. There are currently seven orders of viruses.


title: Consistency analysis of COVID-19 nucleic acid tests and the changes of lung CT

text: Abstract Background COVID-19, the latest outbreak of infectious disease, has caused huge medical challenges to China and the entire globe. No unified diagnostic standard has been formulated. The initial diagnosis remains based on the positive of nucleic acid tests. However, early nucleic acid tests were identified to be negative in some patients, whereas the patients exhibited characteristic CT changes of lung, and positive test results appeared after repeated nucleic acid tests, having caused the failure to diagnose these patients early. The study aimed to delve into the relationships between initial nucleic acid testing and early lung CT changes in patients with COVID-19. Method In accordance with the latest COVID-19 diagnostic criteria, 69 patients diagnosed with COVID-19 treated in the infected V ward of Xiaogan Central Hospital from 2020/1/25 to 2020/2/6 were retrospectively analyzed. The consistency between the first COVID-19 nucleic acid test positive and lung CT changes was studied. In addition, the sensitivity and specificity of CT and initial nucleic acid were studied. Result The Kappa coefficient of initial nucleic acid positive changes and lung CT changes was −1.52. With a positive nucleic acid test as the gold standard, the sensitivity of lung CT was 12.00 %, 95 % CI: 4.6–24.3; with the changes of CT as the gold standard, the sensitivity of nucleic acid positive was 30.16 %, 95 % CI: 19.2−43.0. Conclusion The consistency between the initial positive nucleic acid test and the CT changes in the lungs is poor; low sensitivity was achieved for initial nucleic acid detection and CT changes.


title: Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID‐19 patients in Michigan, United States

text: INTRODUCTION: Higher comorbidity and older age have been reported as correlates of poor outcomes in COVID‐19 patients worldwide, however US data is scarce. We evaluated mortality predictors of COVID‐19 in a large cohort of hospitalized patients in the US. DESIGN: Retrospective, multicenter cohort of inpatients diagnosed with COVID‐19 by RT‐PCR from March 1‐April 1,2020 was performed, and outcome data evaluated from March 1‐April 17, 2020. Measures included demographics, comorbidities, clinical presentation, laboratory values, and imaging on admission. Primary outcome was mortality. Secondary outcomes included length of stay, time to death, and development of acute kidney injury in the first 48‐hours. RESULTS: 1305 patients were hospitalized during the evaluation period. Mean age was 61.0±16.3, 53.8% were male and 66.1% African‐American. Mean BMI was 33.2±8.8 kg/m2. Median Charlson Comorbidity Index (CCI) was 2 (1‐4), 72.6% of patients had at least one comorbidity, with hypertension (56.2%) and diabetes mellitus (30.1%) being the most prevalent. ACE‐I/ARB use and NSAIDs use were widely prevalent (43.3% and 35.7% respectively). Mortality occurred in 200 (15.3%) of patients with median time of 10 (6‐14) days. Age >60 (aOR:1.93,95% CI:1.26‐2.94), and CCI>3 (aOR:2.71,95% CI:1.85‐3.97) were independently associated with mortality by multivariate analyses. NSAIDs and ACE‐I/ARB use had no significant effects on renal failure in the first 48 hours. CONCLUSION: Advanced age and an increasing number of comorbidities are independent predictors of in‐hospital mortality for COVID‐19 patients. NSAIDs and ACE‐I/ARB use prior to admission is not associated with renal failure or increased mortality.


title: Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong Province, China

text: BACKGROUND: Hospital disaster resilience can be defined as a hospital’s ability to resist, absorb, and respond to the shock of disasters while maintaining critical functions, and then to recover to its original state or adapt to a new one. This study aims to explore the status of resilience among tertiary hospitals in Shandong Province, China. METHODS: A stratified random sample (n = 50) was derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong Province, and was surveyed by questionnaire. Data on hospital characteristics and 8 key domains of hospital resilience were collected and analysed. Variables were binary, and analysed using descriptive statistics such as frequencies. RESULTS: A response rate of 82% (n = 41) was attained. Factor analysis identified four key factors from eight domains which appear to reflect the overall level of disaster resilience. These were hospital safety, disaster management mechanisms, disaster resources and disaster medical care capability. The survey demonstrated that in regard to hospital safety, 93% had syndromic surveillance systems for infectious diseases and 68% had evaluated their safety standards. In regard to disaster management mechanisms, all had general plans, while only 20% had specific plans for individual hazards. 49% had a public communication protocol and 43.9% attended the local coordination meetings. In regard to disaster resources, 75.6% and 87.5% stockpiled emergency drugs and materials respectively, while less than a third (30%) had a signed Memorandum of Understanding with other hospitals to share these resources. Finally in regard to medical care, 66% could dispatch an on-site medical rescue team, but only 5% had a ‘portable hospital’ function and 36.6% and 12% of the hospitals could surge their beds and staff capacity respectively. The average beds surge capacity within 1 day was 13%. CONCLUSIONS: This study validated the broad utility of a framework for understanding and measuring the level of hospital resilience. The survey demonstrated considerable variability in disaster resilience arrangements of tertiary hospitals in Shandong province, and the difference between tertiary A hospitals and tertiary B hospitals was also identified in essential areas.


title: The experience on COVID-19 and cancer from an oncology hub institution in Milan, Lombardy Region

text: Abstract The rapid outbreak of the SARS-CoV-2 related disease (COVID-19) has spread rapidly to a pandemic proportion, increasing the demands on health systems for the containment and management of COVID-19. Cancer has been reported as a major risk factor for adverse outcomes of and death from COVID-19. We extracted data from the World Health Organization’s progress reports and from the Italian Council of Medicine. In addition, we retrieved clinical data on cancer patients with confirmed COVID-19 in our Institution. As of April 2nd, 2020, 110 574 COVID-19 cases and 13 157 deaths have been described in Italy, representing a global share of 5.1% and 28.9% for incidence and mortality, respectively. In Italy, we report the analysis of the Italian Medical Council on 909 patients who died from COVID-19, of whom 16.5% were cancer patients. The population was enriched with subjects with multiple co-morbid non-communicable diseases, with less than 1% of the population presenting no co-morbid conditions. At the patient level, we identified nine patients referred to our department in the last two months who were receiving standard of care or experimental medications in the curative and palliative settings. The median age was 68 years (range: 42–79 years), and patients carried a median of one co-morbid condition (0–2); two out of nine patients presented with severe COVID-19 presentation, and were receiving inpatient care. None of the patients receiving immunotherapy experienced severe adverse outcomes, and four patients were discharged with complete reversal of the clinical syndrome and SARS-CoV-2 clearance. Learning from the experience of countries with a high burden, efforts must be made to assure the access of cancer patients to treatments, prioritizing the cancer health interventions based on their intrinsic value, and limiting the exposure to an unacceptable risk of infection for both health providers and patients. Any significant work in the design and implementation of health system actions, including in clinical care, must be framed as an initiative under the Global Response Agenda and through a community approach, with the intention of pursuing common goals to tackle COVID-19 and cancer, as ‘One Community’ working for ‘One Health’s.


title: Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease

text: INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman–Kärber method and reported as median tissue culture infectious dose (TCID(50))/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved ≥ 99.99% virucidal activity against SARS-CoV-2, corresponding to ≥ 4 log(10) reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00316-3) contains supplementary material, which is available to authorized users.


title: Preparation of an intensive care unit in France for the reception of a confirmed case of Ebola virus infection

text: Abstract The current Ebola Virus Disease (EVD) outbreak in West Africa is a major challenge for the worldwide medical community. On April 29th 2015, the World Health Organization (WHO) declared 26,277 infected cases; among them, 10,884 have deceased. The epidemic is still ongoing, particularly in Sierra Leone. It is now clear that northern countries will be implicated in the care of EVD patients, both in the field and back at home. Because of the severity of EVD, a fair amount of patients may require intensive care. It is highly probable that intensive care would be able to significantly reduce the mortality linked with EVD. The preparation of a modern Intensive Care Unit (ICU) to treat an EVD patient in good conditions requires time and specific equipment. The cornerstone of this preparation includes two main goals: treating the patient and protecting healthcare providers. Staff training is time consuming and must be performed far in advance of patient arrival. To be efficient, preparation should be planned at a national level with help from public authorities, as was the case in France during the summer of 2014. Due to the severity of the disease, the high risk of transmission and scarce knowledge on EVD treatment, our propositions are necessarily original and innovative. Our review includes four topics: a brief report on the actual outbreak, where to receive and hospitalize the patients, the specific organization of the ICU and finally ethical aspects.


title: Initial chest CT findings in COVID-19: correlation with clinical features

text: 目的: 分析2019 冠状病毒病 (COVID-19) 患者首次胸部 CT 影像表现及其与临床表现 (包括发热症状、实验室检查) 的相关性。 创新点: 初步探索 COVID-19 肺部病灶与临床数据的相关性, 对评估 COVID-19 患者提供一定的依据。 方法: 纳入 2020 年 1 月 16 日至 2020 年 2 月 6 日入院的 36 例 COVID-19 患者, 回顾性分析首次胸部 CT 的影像学表现, 包括影像特征、分布模式、累及 范围等, 并进一步分析其与临床特征 (包括发病 时间、发热症状、白细胞计数等) 的相关性。 结论: 结果发现, 在自然病程中, COVID-19 肺部病变与发病时间显著相关, 特别是发热症状。COVID-19 病变范围与淋巴细胞计数呈负相关, 淋巴细胞减少可能是 COVID-19 进展的标志之 一。


title: After the Megafires: What Next for Australian Wildlife?

text: The 2019–2020 megafires in Australia brought a tragic loss of human life and the most dramatic loss of habitat for threatened species and devastation of ecological communities in postcolonial history. What must be done now to keep impacted species from extinction? What can be done to avoid a repeat of the impacts of such devastating bushfires? Here, we describe hard-won lessons that may also be of global relevance.


title: Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China

text: Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1–3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.


Emergency department infection control strategies in response to COVID‐19


title: Perinatal depressive and anxiety symptoms of pregnant women along with COVID-19 outbreak in China

text: Abstract Background On January 20, 2020, a new coronavirus epidemic with “human-to-human” transmission was officially announced by the Chinese government, which caused significant public panic in China. Pregnant women may be particularly vulnerable and in special need for preventative mental health strategies. Thus far, no reports exist to investigate the mental health response of pregnant women to the COVID-19 outbreak. Objective The aim of the present study is to examine the impact of COVID-19 outbreak on the prevalence of depressive and anxiety symptoms and the corresponding risk factors among pregnant women across China. Study Design A multi-center cross-sectional study was initiated in early December 2019 to identify mental health concerns in pregnancy using the Edinburgh Postnatal Depression Scale (EPDS). This study provided a unique opportunity to compare the mental status of pregnant women before and after the announcement of the COVID-19 epidemic. A total of 4124 pregnant women during their third trimester from 25 hospitals in 10 provinces across China were examined in this cross-sectional study from January 1 to February 9, 2020. Of these women, 1285 were assessed after January 20, 2020 when the coronavirus epidemic was publically announced and 2839 were assessed before this pivotal time point. The internationally recommended EPDS was used to assess maternal depression and anxiety symptoms. Prevalence rates and risk factors were compared between the pre and post study groups. Results Pregnant women assessed after the declaration of COVID-19 epidemic had significantly higher rates of depressive symptoms (26.0% vs 29.6%, P=0.02) than women assess pre-epidemic announcement. These women were also more likely to endorse thoughts of self-harm (P=0.005). The depressive rates were positively associated with the number of newly-confirmed COVID-19 cases (P=0.003), suspected infections (P=0.004), and death cases per day (P=0.001). Pregnant women who were underweight pre-pregnancy, primiparous, < 35 years old, employed full-time, middle income, and had appropriate living space were at increased risk to develop depressive and anxiety symptoms during the outbreak. Conclusion Major life-threatening public health events such as the COVID-19 outbreak may increase the risk for mental illness among pregnant women including thoughts of self-harm. Strategies targeting maternal stress and isolation such as effective risk communication and the provision of psychological first aid may be particularly useful to prevent negative outcomes for women and their fetuses.


title: Numerical study of the transport of droplets or particles generated by respiratory system indoors

text: Abstract The outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS), has spread to many countries in the world. SARS may infect human bodies by the tiny droplets or particles carrying various virus and bacteria, which are generated by the respiratory system of infected patients. This paper presents the numerical analysis of the influence of generating ways of the droplets or particles on the transport and distribution of the droplets or particles indoors. The drift flux model, which considers the settling of particles or droplets under the effect of gravitational sedimentation, is adopted to simulate the droplets transport and distribution indoors during respiration and sneezing or coughing process, while the simplified model for solving the continuous fluid flow is combined. Two different cases considering the normal respiration and coughing or sneezing are studied, respectively, and two different outlet velocities from the mouth for the sneezing or coughing process are considered. The results show that droplets or particles generated by normal breathing process transport a relatively short distance, while droplets or particles generated during coughing or sneezing may travel much longer distances, which may pose adverse effect on human bodies for defending the SARS or other infectious diseases.


title: Fulminant hemophagocytic lymphohistiocytosis secondary to a reactivated EBV infection: A case report

text: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive inflammatory syndrome that results from inappropriate activation of the immune system. HLH has a high mortality if not treated. We describe a case of a fulminant HLH, associated with a reactivation of an EBV infection. The patient responded well to steroid treatment.


title: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events

text: BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.


title: Hydrodiplomacy and adaptive governance at the U.S.-Mexico border: 75 years of tradition and innovation in transboundary water management

text: The United States and Mexico have engaged in hydrodiplomacy—a practice of transboundary water management that blends water diplomacy and science diplomacy--for more than 75 years, since the adoption of the Treaty of 1944 and the creation of the International Boundary and Water Commission. We examine six major turning points in U.S.-Mexico hydrodiplomacy to ascertain the key factors in the region’s history of resolving transboundary water issues. We find that recognized adaptive governance indicators—such as social learning, sustained relationships, flexible governance mechanisms, and state and non-state networks are essential elements of hydrodiplomacy. Our research suggests that robust and foundational institutions comprise another key indicator of adaptive governance specifically in transboundary contexts. A commitment to both science and diplomacy have been important components underlying the effectiveness of hydrodiplomacy in the border region. Binational networks involving diverse state and non-state actors at multiple scales have increasingly played a pivotal role in shaping desirable hydrodiplomatic outcomes in the region.


title: Generation and characterization of bat-induced pluripotent stem cells

text: Induced pluripotent stem cells (iPSCs) were first generated from mouse embryonic fibroblasts in the year 2006. These cells resemble the typical morphology of embryonic stem cells, express pluripotency markers, and are able to transmit through germlines. To date, iPSCs of many species have been generated, whereas generation of bat iPSCs (biPSCs) has not been reported. To facilitate in-depth study of bats at the molecular and cellular levels, we describe the successful derivation of biPSCs with a piggyBac (PB) vector that contains eight reprogramming factors Oct4, Sox2, Klf4, Nanog, cMyc, Lin28, Nr5a2, and miR302/367. These biPSCs were cultured in media containing leukemia inhibitory factor and three small molecule inhibitors (CHIR99021, PD0325901, and A8301). They retained normal karyotype, displayed alkaline phosphatase activity, and expressed pluripotency markers Oct4, Sox2, Nanog, TBX3, and TRA-1-60. They could differentiate in vitro to form embryoid bodies and in vivo to form teratomas that contained tissue cells of all three germ layers. Generation of biPSCs will facilitate future studies on the mechanisms of antiviral immunity and longevity of bats at the cellular level.


title: Novel coronavirus disease 2019 (COVID-19): relationship between chest CT scores and laboratory parameters

text: PURPOSE: To quantify the severity of 2019 novel coronavirus disease (COVID-19) on chest CT and to determine its relationship with laboratory parameters. METHODS: Patients with real-time fluorescence polymerase chain reaction (RT-PCR)–confirmed COVID-19 between January 01 and February 18, 2020, were included in this study. Laboratory parameters were retrospectively collected from medical records. Severity of lung changes on chest CT of early, progressive, peak, and absorption stages was scored according to the percentage of lung involvement (5 lobes, scores 1–5 for each lobe, range 0–20). Relationship between CT scores and laboratory parameters was evaluated by the Spearman rank correlation. The Bonferroni correction adjusted significance level was at 0.05/4 = 0.0125. RESULTS: A total of 84 patients (mean age, 47.8 ± 12.0 years [standard deviation]; age range, 24–80 years) were evaluated. The patients underwent a total of 339 chest CT scans with a median interval of 4 days (interquartile range, 3–5 days). Median chest CT scores peaked at 4 days after the beginning of treatment and then declined. CT score of the early stage was correlated with neutrophil count (r = 0.531, P = 0.011). CT score of the progressive stage was correlated with neutrophil count (r = 0.502, P < 0.001), white blood cell count (r = 0.414, P = 0.001), C-reactive protein (r = 0.511, P < 0.001), procalcitonin (r = 0.423, P = 0.004), and lactose dehydrogenase (r = 0.369, P = 0.010). However, CT scores of the peak and absorption stages were not correlated with any parameter (P > 0.0125). No sex difference occurred regarding CT score (P > 0.05). CONCLUSION: Severity of lung abnormalities quantified on chest CT might correlate with laboratory parameters in the early and progressive stages. However, larger cohort studies are necessary.


title: Could IL-17 represent a new therapeutic target for the treatment and/or management of COVID-19-related respiratory syndrome? This paper is dedicated to Sofia Maione born during COVID-19 outbreak.

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title: Mobile ECMO team for inter-hospital transportation of patients with ARDS: a retrospective case series

text: INTRODUCTION: Transport of patients undergoing extracorporeal membrane oxygenation is currently available in 5 referral centers in our country. METHODS: Retrospective case series of patients managed by our mobile extracorporeal membrane oxygenation team and transferred to San Gerardo University Hospital from December 2004 to December 2012. RESULTS: 42 patients were transported. The mean age was 42.11 (standard deviation ±18.11) years, with a range between 2 years and 70. 14 patients were females (33%) and 28 males (67%). The average transport distance was 121.69 km (±183.08) with a range between 9 km and 1044 Km. The mission’s mean time was equal to 508 minutes (±185) with range of 120-960 minutes. 29 patients (69%) were transported with extracorporeal membrane oxygenation support, while 13 patients (31%) were transported with conventional ventilation. In 28 patients (97%) a veno-venous bypass was utilized, while in one case (3%) a Veno-Arterial cannulation was performed. 32 patients survived (76%) and have been discharged alive from hospital. No major clinical or technical issues were observed during the transport. CONCLUSIONS: According to our data, we conclude that a dedicated mobile team allowed safe ground transportation of patients with severe acute lung injury to our tertiary care institution.


Students’ Perceptions on Dental Education in the Wake of the COVID‐19 Pandemic


title: Receptor-Induced Thiolate Couples Env Activation to Retrovirus Fusion and Infection

text: According to current models of retrovirus infection, receptor binding to the surface subunit (SU) of the envelope glycoprotein (Env) triggers a conformational change in the transmembrane subunit (TM) that mediates virus fusion to cell membranes. To understand how this occurs, we investigated the role of the receptor Tva in avian leukosis virus-A (ALV-A) infection. We find that Tva binding induced the formation of a reactive thiolate on Cys38 (Cys38-S(−)) in SU. Both chemical and genetic inactivation of Cys38-S(−) completely abrogated ALV fusion and infection. Remarkably, Cys38-S(−) does not mediate isomerization of the SU-TM disulfide bond and is not required for Tva-induced activation of TM, including pre-hairpin association with membranes and low pH assembly of helical bundles. These findings indicate that, contrary to current models, receptor activation of TM is not sufficient for ALV fusion and infection and that formation of a reactive thiolate is an additional receptor-dependent step.


title: An efficient and tunable route to AG7088, a rhinovirus protease inhibitor

text: Abstract Aldol reaction of N,N-dibenzyl valinal with propiolic acid ethyl ester derived lithium reagent provides anti-aminoalcohol 8 and syn-aminoalcohol 9 , which are converted into the lactone 6 via two different routes. Alkylation of 6 followed by lactone ring opening afford the acid 2a , which is coupled with the amine 3 and 5-methylisoxazole-3-carboxylate acid 1 , respectively, to deliver AG7088.


title: Avian influenza virus, Streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in China

text: The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the ‘well-known’ reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China.


title: Respiratory Viral Infections in Immunocompetent and Immunocompromised Persons

text: Abstract The acute respiratory illnesses are the most common type of acute illness in the United States today. The respiratory viruses—which include influenza viruses, parainfluenza viruses, respiratory syncytial virus (RSV), rhinoviruses, coronaviruses, and adenoviruses—cause the majority of these illnesses. Some of these viruses cause illness throughout the year, whereas others are most common in winter. All population groups experience these infections and illnesses. As the number of elderly persons and those with underlying disease increases, awareness is growing that these common infections can have serious consequences. This has recently been emphasized for immunocompromised persons. At the M.D. Anderson Cancer Center (MDACC), infection surveillance of mostly hospitalized adults with leukemia or a recent bone marrow transplant yielded a respiratory virus from 181 of 668 (27.1%) respiratory illness episodes. In descending order of frequency, infections with RSV, rhinoviruses, influenza viruses, parainfluenza viruses, and adenoviruses were detected in each of three surveillance years. High frequencies of nosocomial acquisition occurred, as has been noted in prior reports. Similarly, persistence of infection and high frequencies of pneumonia and death among infected patients occurred, which have also been noted earlier. At MDACC, pneumonia occurred in 58–78% of infected patients, and 22–44% died. The role of the virus infection in many cases of pneumonia is uncertain, but death from pure viral pneumonia is well documented. A number of immune deficiencies in this patient population and options for control of these infections have been described that can, respectively, account for the medical problem and provide ways to approach prevention and treatment.


title: Effect of Glycyrrhizin on Pseudomonal Skin Infections in Human-Mouse Chimeras

text: In our previous studies, peripheral blood lineage(−)CD34(+)CD31(+) cells (CD31(+) IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null) mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+) IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+) IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD(50) dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+) IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+) IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.


title: An appraisal of different methods for the detection of the walnut strain of cherry leafroll virus

text: Abstract Three methods were evaluated for the detection of cherry leafroll virus: ELISA, dot-blot and reverse transcriptional polymerase chain reaction (RT-PCR). Dot-blot and RT-PCR were carried out in crude plant extracts without any further RNA purification. Dot-blot hybridization using a 32P-labelled DNA probe was as sensitive as previously reported ELISA results for cherry leafroll virus detection. The most sensitive method was RT-PCR, which amplified a specific fragment of 448 bp from the 3' untranslated region of both viral genomic RNAs. RT-PCR was used to detect cherry leafroll virus in infected walnut buds and twigs.


title: Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus

text: In the eukaryotic cell, both secreted and plasma membrane proteins are synthesized at the endoplasmic reticulum, then transported, via the Golgi complex, to the cell surface(1–4). Each of the compartments of this transport pathway carries out particular metabolic functions(5–8), and therefore presumably contains a distinct complement of membrane proteins. Thus, mechanisms must exist for localizing such proteins to their respective destinations. However, a major obstacle to the study of such mechanisms is that the isolation and detailed analysis of such internal membrane proteins pose formidable technical problems. We have therefore used the E1 glycoprotein from coronavirus MHV-A59 as a viral model for this class of protein. Here we present the primary structure of the protein, determined by analysis of cDNA clones prepared from viral mRNA. In combination with a previous study of its assembly into the endoplasmic reticulum membrane(9), the sequence reveals several unusual features of the protein which may be related to its intracellular localization.