title: The Psychological Causes of Panic Buying Following a Health Crisis

text: Attributed to the recent COVID-19 pandemic, panic buying is now a frequent occurrence in many countries, leading to stockouts and supply chain disruptions. Consequently, it has received much attention from academics and the retail industry. The aim of this study is to review, identify, and synthesise the psychological causes of panic buying, which is a relatively new and unexplored area in consumer behaviour research. A systematic review of the related literature is conducted. The review suggests that panic buying is influenced by (1) individuals’ perception of the threat of the health crisis and scarcity of products; (2) fear of the unknown, which is caused by negative emotions and uncertainty; (3) coping behaviour, which views panic buying as a venue to relieve anxiety and regain control over the crisis; and (4) social psychological factors, which account for the influence of the social network of an individual. This study contributes to the literature by consolidating the scarce and scattered research on the causes of panic buying, drawing greater theoretical insights into each cause and also offers some implications for health professionals, policy makers, and retailers on implementing appropriate policies and strategies to manage panic buying. Recommendations for future research are also provided.


title: SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management

text: The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up–to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.


title: Efficacy and safety of antibiotic agents in children with COVID-19: a rapid review.

text: Background The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. Methods We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. Results Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted OR 0.84, 95% CI: 0.47-1.51, P=0.56) and improvement in MERS-CoV RNA clearance (adjusted HR 0.88, 95% CI: 0.47-1.64, P=0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. Conclusions The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.


title: Staging Science: Authoritativeness and Fragility of Models and Measurement in the COVID‐19 Crisis

text: In the COVID‐19 crisis, society pins its hopes on science to play an authoritative role in reducing uncertainty and ambiguity. But is science up to the task? This is far from self‐evident. The demands on science in times of crisis run counter to the values of good, normal science. Crisis science needs to be fast, univocal, personalized, and direct, while normal science is slow, contentious, collective, and sensitive to complexity. Science can only play its atypical role if it is staged in the public arena. Some patterns of staging stand out: personalization, visualization, and connection to lived experiences. So far, the staging of science has been successful, but it is fragile. The COVID‐19 crisis shows the potential of well‐staged forms of alliance between science and policy, but when the general assumption is that scientists will “solve” societal “problems,” the staging of science has gone too far.


title: Interferon-α2b Treatment for COVID-19

text: The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.


title: Public Health Interventions and SARS Spread, 2003

text: The 2003 outbreak of severe acute respiratory syndrome (SARS) was contained largely through traditional public health interventions, such as finding and isolating case-patients, quarantining close contacts, and enhanced infection control. The independent effectiveness of measures to "increase social distance" and wearing masks in public places requires further evaluation. Limited data exist on the effectiveness of providing health information to travelers. Entry screening of travelers through health declarations or thermal scanning at international borders had little documented effect on detecting SARS cases; exit screening appeared slightly more effective. The value of border screening in deterring travel by ill persons and in building public confidence remains unquantified. Interventions to control global epidemics should be based on expert advice from the World Health Organization and national authorities. In the case of SARS, interventions at a country's borders should not detract from efforts to identify and isolate infected persons within the country, monitor or quarantine their contacts, and strengthen infection control in healthcare settings.


title: Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

text: Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.


title: Supply chain contagion and the role of industrial policy

text: The COVID-19 pandemic triggered a major disruption in global value chains (GVCs) that pushed the global economy into a recession that promises to be worse than the 2008 crisis. This article illustrates the mechanisms through which the COVID-19 pandemic affected GVCs in the context of a changing configuration of the global economy. In particular, it is argued that GVCs became the main transmission channels of “economic contagion”. Finally, we posit that the pandemic provides an opportunity to revive the role of industrial policy as to govern the landslides of a world economy constantly pressured by globalization and deglobalization forces.


title: Outbreak analysis with a logistic growth model shows COVID-19 suppression dynamics in China

text: China reported a major outbreak of a novel coronavirus, SARS-CoV2, from mid-January till mid-March 2020. We review the epidemic virus growth and decline curves in China using a phenomenological logistic growth model to summarize the outbreak dynamics using three parameters that characterize the epidemic’s timing, rate and peak. During the initial phase, the number of virus cases doubled every 2.7 days (range 2.2–4.4 across provinces). The rate of increase in the number of reported cases peaked approximately 10 days after suppression measures were started on 23–25 January 2020. The peak in the number of reported sick cases occurred on average 18 days after the start of suppression measures. From the time of starting measures till the peak, the number of cases increased by a factor 39 in the province Hubei, and by a factor 9.5 for all of China (range: 6.2–20.4 in the other provinces). Complete suppression took up to 2 months (range: 23-57d.), during which period severe restrictions, social distancing measures, testing and isolation of cases were in place. The suppression of the disease in China has been successful, demonstrating that suppression is a viable strategy to contain SARS-CoV2.


title: Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein

text: The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 7,000,000 infections and 400,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARSCoV-2 spike (S) protein, which mediates the host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). In the context of vaccine design, similar to many other viruses, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the glycan shield and the protein structure, stability, and dynamics. End-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of SARS-CoV-2 S protein, which can be harnessed for vaccine development. In addition, a dynamic analysis of the main antibody epitopes is provided. Finally, beyond shielding, a possible structural role of N-glycans at N165 and N234 is hypothesized to modulate and stabilize the conformational dynamics of the spike’s receptor binding domain, which is responsible for ACE2 recognition. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, which may be exploited by therapeutic efforts targeting this essential molecular machine.


title: Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies

text: No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets was performed. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.


title: Changes in clinical and laboratory features of Kawasaki disease noted over time in Daejeon, Korea

text: BACKGROUND: Kawasaki disease (KD) becomes one of the common diseases in Korea. Changes in clinical features and laboratory findings of KD were evaluated over a period of 10 years. METHODS: We reviewed the medical records of KD patients and compared the clinical and laboratory features of two KD patient groups: those admitted from 2000 to 2004 (group A, 284 cases) and those admitted from 2010 to 2014 (group B, 331 cases). RESULTS: There were a total of 615 KD patients (mean age: 29.7 months; male-to-female ratio = 1.6:1), including 228 incomplete KD patients. Incomplete KD patients had milder values in some laboratory indices. The preadmission and total fever durations were longer in group A than in group B. The proportion of incomplete KD was higher in group B, but incidence of coronary artery lesions (CALs) was lower. For laboratory indices, the C-reactive protein and follow-up platelet values were lower, and the hemoglobin and albumin values were higher in group B. The same clinical and laboratory findings were confirmed in the KD subgroups; those with the same fever duration of 5 or 6 days and same ages, those with complete KD, and those with incomplete KD in the two different time periods. CONCLUSIONS: Our findings suggest that clinical features of KD tend to be milder over time and manifest in a higher incidence of incomplete KD, lower incidence of CALs, and less severe laboratory findings in recent KD patients in Korea compared with their historic counterparts.


title: Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I(2)=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I(2)=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I(2)=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.


title: The "influenza vaccine" – benefit, risk, costs

text: More than 20 million people died during the pandemic 'flu season 1918/1919, the largest influenza pandemic of the 20th century. Since then, influenza A virus infections have been known as a serious cause of morbidity and mortality in the whole world population. Although specific and effective antiviral therapeutics (neuraminidase inhibitors) are available, vaccinating against influenza is the first preventative measure. In Germany, influenza immunization has been yearly recommended by the current vaccination committee of the Robert Koch Institute (STIKO). Vaccinations have a special indication in elderly persons >60 years, patients with chronic diseases and persons with higher risk of influenza infections. In general, inactivated vaccines are well tolerated by recipients. The cost effectiveness of influenza vaccination has been well established. Although the benefit of annual influenza vaccination especially for the elderly and risk groups is beyond doubt, a low acceptance of vaccine recommendations has been noticed in Germany to date.


title: Resilience resistance: The challenges and implications of urban resilience implementation

text: Growing concern about major threats, including climate change, environmental disasters, and other hazards, is matched with the increased interest and appeal of the concept of urban resilience. Much scholarly attention has focused on how to define urban resilience, in addition to raising questions about its applicability and usefulness. But those debates typically overlook questions of implementation. Implementation is important not only for how cities respond to threats but also because it can influence how urban resilience is perceived, discussed, and understood. The policy literature suggests that implementation is rarely straightforward and has ideological and normative perspectives embedded within it. Building on this literature, this paper argues that urban resilience implementation raises its own conceptual questions for both theory and practice. Further, implementing urban resilience entails its own unique challenges, such as extensive coordination, maintaining adaptability, divergent time horizons, and diverse outcomes. The paper also introduces the idea of resilience resistance as a new challenge for urban resilience. Resistance refers to the condition in which governance systems inherently develop barriers to change, flexibility, and adaptability through implementation. Several aspects of resistance are highlighted, including fatigue, complacency, and overconfidence. However, the implementation process can also have unintended positive effects on a city's capacity to prepare for and respond to shocks.


title: Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions

text: BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.


title: Emergency department personal protective equipment requirements following out‐of‐hospital chemical biological or radiological events in Australasia

text: Recent events have led to a revision in ED equipment, preparedness and training for disasters. However, clinicians must still decide when, and what level of personal protection is required when a toxic threat exists. If possible, clear, simple and achievable protocols are required in such situations. Following an off‐site Australasian chemical biological or radiological incident, current evidence indicates that the initial receiving ED staff will be adequately protected from all known chemical biological and radiological inhalational threats by wearing a properly fitted P2 (N95) mask, or its equivalent. Protection from serious contact injury is offered by wearing double gloves, disposable fluid‐repellent coveralls or gown, eye protection, surgical mask, and ideally, a cap and shoe covers; in conjunction with universal precautions and procedures.


title: Clinical translation of RNAi-based treatments for respiratory diseases

text: The ability to harness the RNA interference (RNAi) mechanism as a potential potent therapeutic has attracted great interest from academia and industry. Numerous preclinical and recent clinical trials have demonstrated the effectiveness of RNAi triggers such as synthetic small interfering RNA (siRNA). Chemical modification and delivery technologies can be utilized to avoid immune stimulation and improve the bioactivity and pharmacokinetics. Local application to the respiratory epithelia allows direct access to the site of respiratory pathogens that include influenza and respiratory syncytial virus (RSV). This review outlines the essential steps required for the clinical translation of RNAi-based respiratory therapies including disease and RNA target selection, siRNA design, respiratory barriers, and delivery solutions. Attention is given to antiviral therapies and preclinical evaluation with focus on the current status of anti-RSV clinical trials.


title: A COVID-19 Risk Assessment for the US Labor Force

text: The consequences of COVID-19 infection varies substantially based on individual social risk factors and predisposing health conditions. Understanding this variability may be critical for targeting COVID-19 control measures, resources and policies, including efforts to return people back to the workplace. We compiled individual level data from the National Health Information Survey and Quarterly Census of Earnings and Wages to estimate the number of at-risk workers for each US county and industry, accounting for both social and health risks. Nearly 80% of all workers have at least one health risk and 11% are over 60 with an additional health risk. We document important variation in the at-risk population across states, counties, and industries that could provide a strategic underpinning to a staged return to work.


title: Detection of novel ferret coronaviruses and evidence of recombination among ferret coronaviruses

text: In an epidemiological study of ferret coronaviruses (FRCoVs), novel FRCoV strains (Saitama-1 and Aichi-1) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequence analysis of partial RNA-dependent RNA polymerase (RdRp) genes. Phylogenetic analysis indicated that these strains belonged to different clusters from other FRCoV strains. Next, the nucleotide sequence of the 3′-terminal region of Saitama-1 (8271 bases) strain was determined and compared with those of the other FRCoVs, indicating that the Saitama-1 strain differed from the previously reported MSU-1 and MSU-2 strains in the regions encoding spike (S) protein, nucleocapsid, and open reading frame 7b. Furthermore, the results of SimPlot analysis indicated that FRCoV (MSU-2 strain) emerged via a recombination event of S protein between the MSU-1 and Saitama-1 strains. This mechanism is similar to that responsible for the emergence of type II feline coronavirus. This information will be useful for understanding the pathogenesis of FRCoV in ferrets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-016-1365-3) contains supplementary material, which is available to authorized users.


title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

text: The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.


title: Role of the Toll Like Receptor (TLR) Radical Cycle in Chronic Inflammation: Possible Treatments Targeting the TLR4 Pathway

text: Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many “civilization” disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.


title: First evidence of host range expansion in virophages and its potential impact on giant viruses and host cells

text: Virophages are satellite-like double stranded DNA viruses whose replication requires the presence of two biological entities, a giant virus and a protist. In this report, we present the first evidence of host range expansion in a virophage. We demonstrated that the Guarani virophage was able to spontaneously expand its viral host range to replicate with two novel giant viruses that were previously nonpermissive to this virophage. We were able to characterize a potential genetic determinant of this cross-species infection. We then highlighted the relevant impact of this host adaptation on giant viruses and protists by demonstrating that coinfection with the mutant virophage abolishes giant virus production and rescues the host cell population from lysis. The results of our study help to elucidate the parasitic lifestyle of virophages and their interactions with giant viruses and protists.


title: A decade of RNA virus metagenomics is (not) enough

text: Abstract It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.


title: Porcine Deltacoronavirus Nucleocapsid Protein Suppressed IFN-β Production by Interfering Porcine RIG-I dsRNA-Binding and K63-Linked Polyubiquitination

text: Porcine deltacoronavirus (PDCoV) is a newly detected porcine coronavirus causing serious vomiting and diarrhea in piglets, especially newborn piglets. There has been an outbreak of PDCoV in worldwide since 2014, causing significant economic losses in the pig industry. The interferon (IFN)-mediated antiviral response is an important component of virus-host interactions and plays an essential role in inhibiting virus infection. However, the mechanism of PDCoV escaping the porcine immune surveillance is unclear. In the present study, we demonstrated that the PDCoV nucleocapsid (N) protein antagonizes porcine IFN-β production after vesicular stomatitis virus (VSV) infection or poly(I:C) stimulation. PDCoV N protein also suppressed the activation of porcine IFN-β promoter when it was stimulated by porcine RLR signaling molecules. PDCoV N protein targeted porcine retinoic acid-inducible gene I (pRIG-I) and porcine TNF receptor associated factor 3 (pTRAF3) by directly interacting with them. The N-terminal region (1–246 aa) of PDCoV N protein was important for interacting with pRIG-I and interfere its function. We confirmed that PDCoV N antagonizes IFN-β production by associating with pRIG-I to impede it from binding double-stranded RNA. Furthermore, porcine Riplet (pRiplet) was an important activator for pRIG-I by mediating the K63-linked polyubiquitination. However, PDCoV N protein restrained the pRiplet binding pRIG-I to inhibit pRIG-I K63-linked polyubiquitination. Taken together, our results revealed a novel mechanism by which PDCoV N protein interferes with the early activation of pRIG-I in the host antiviral response. The novel findings provide a new insight into PDCoV on evading the host innate immune response and may provide new therapeutic targets and more efficacious vaccines strategies for PDCoV infections.


title: Troponin I, a risk factor indicating more severe pneumonia among patients with novel coronavirus infected pneumonia

text: BACKGROUND: In December 2019, a novel communicable disease, novel coronavirus infected pneumonia (NCIP) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) broke out. We aimed to analyze the characteristics and severity of patients with myocardial damage in NCIP. METHODS: We enrolled 215 adult patients with NCIP from January 2020 to February 2020. Outcomes were followed up until March 1st, 2020. RESULTS: 28.37% of the total patients showed increased level of TnI (> 0.040 ng/ml). Patients were older and had more cardiovascular complications in increased TnI group. Higher CRP, NT-proBNP, lower immune CD3, CD4 and CD8 cell account and more involved lobes detected by CT scan in the lung were observed in increased TnI group. Patients with elevated TnI had higher CRUB-65 scores and were more likely given glucocorticoid therapy and mechanical ventilation than patients in normal TnI group. CONCLUSIONS: Markers of cardiomyocyte injury were elevated not least in elderly males with pre-existing cardiovascular disease. Patients with elevated TnI presented more severe situation, leading to multiple organ dysfunctions, which appeared as a pivotal feature of patients with NCIP that requires attention by clinicians in order to provide necessary treatment as soon as possible and improve patients' outcomes.


title: Les virus des eaux usées et leur élimination au cours des traitements des effluents pollués

text: Abstract Viruses are a biological pollution in wastewaters. Their elimination results from treatment processes of polluted effluents in the sewage treatment plant or in the lagooning pilot plant. Bacteriophages are regarded as viruses models and as indicators of faecal contamination. In an expiremental study, two pilot plants laboratories have been used (natural lagooning and activated sludge pilot) to follow and evaluate the elimination rate of somatic coliphage X-174 or the ARN F-specific one MS2. The two phages removal, ranging to 99 % in the two systems, are related with previous values on enteric viruses. The main factors of viral removal and inactivation (adsorption to solid matters, microbial activities, solar radiations, dissolved matters) have been studied too. Adsorption of infectious particles to solid matters is a very significant process. This was obtained in the pilot plant laboratory experiment and in in vitro study (X-174 or MS2 in the presence of the kaolinite or the montmorillonite). Otherwise, 12 hours of solar rays exposition were efficient ro inactivate nearly the whole phagic suspension. The ciliate protozoan Tetrahymena pyriformis does not seem to have an important role for elimination of phages (X-174 and MS2.


title: Chloroquine and Hydroxychloroquine Retinal Toxicity Consideration in the Treatment of COVID-19

text: The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.


title: Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

text: Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.


MERS–Related Betacoronavirus in Vespertilio superans Bats, China


title: A rare Cryptosporidium parvum genotype associated with infection of lambs and zoonotic transmission in Italy

text: An outbreak of cryptosporidiosis occurred in a mixed sheep/cattle farm of Central Italy in October 2011. A total of 450 ovines (250 sheep and 200 lambs) and 140 bovines (130 cows and 10 calves) were housed in two separated units, at the time of the outbreak. About half of the lambs had diarrhea due to Cryptosporidium sp. with a mortality rate of 80%; calves were not infected. Genomic DNA was extracted from an archived slide and from fecal specimens, and the parasite was identified as Cryptosporidium parvum by PCR and sequence analysis at the CpA135 gene. Genotyping at the GP60 gene showed the presence of a very rare genotype, IIaA20G2R1. Shortly after the outbreak was identified, the son of the farm's owner, aged 18 months, experienced an acute gastroenteritis and was hospitalized due to recurrent episodes of diarrhea, fever, vomiting and lack of appetite. The feces tested negative for bacteria and viruses, whereas cryptosporidiosis was diagnosed by microscopy and an immunochromatographic test. Molecular typing identified the C. parvum genotype IIaA20G2R1 in the feces of the child. This is the first case of transmission of cryptosporidiosis in Italy involving lambs as source of oocysts infectious to humans.


title: Enterovirus type 71 2A protease functions as a transcriptional activator in yeast

text: Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis.


title: Scientific and Standardization Committee Communication: Clinical Guidance on the Diagnosis, Prevention and Treatment of Venous Thromboembolism in Hospitalized Patients with COVID‐19

text: The novel coronavirus disease of 2019 (COVID‐19) pandemic, as declared by the World Health Organization, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2). Cardiovascular disease and, in particular, venous thromboembolism (VTE) has emerged as an important consideration in the management of hospitalized patients with COVID‐19. The diagnosis of VTE using standardized objective testing is problematic in these patients, given the risk of infecting non‐COVID‐19 hospitalized patients and hospital personnel, coupled with the usual challenges of performing diagnostic testing in critically‐ill patients. Early reports suggest a high incidence of VTE in hospitalized COVID‐19 patients, particularly those with severe illness, that is similar to the high VTE rates observed in patients with other viral pneumonias, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS‐CoV).


title: Designing Graduate Training Programs in Conservation Medicine—Producing the Right Professionals with the Right Tools

text: New challenges to human, animal, and ecosystem health demand novel solutions: New diseases are emerging from new configurations of humans, their domestic animals and wildlife; new pressures on once robust and resilient ecosystems are compromising their integrity; synthetic compounds and engineered organisms, new to the natural world, are spreading unpredictably around the globe. Globalization provides opportunities for infectious organisms to gain access to new hosts, changing in distribution and virulence. What type of training should be developed to provide professionals with the right tools to meet these challenges? In this article, we offer recommendations for developing academic programs in conservation medicine. We discuss the need for, and the advantages to, using a conservation medicine approach to address real world situations and present illustrations of how this is applied today. We suggest a core set of skills that are needed in a conservation medicine practitioner, and recommend key considerations for designing new conservation medicine training programs. We review existing programs that offer conservation medicine content, and provide examples of where opportunities exist for those interested in pursuing a conservation medicine career.


title: Addressing a National Crisis: The Spine Hospital and Department's Response to the COVID-19 Pandemic in New York City

text: In a very brief period, the COVID-19 pandemic has swept across the planet leaving governments, societies and healthcare systems unprepared and under-resourced. New York City now represents the global viral epicenter with roughly one third of all mortalities in the United States. To date, our hospital has treated thousands of COVID-19 positive patients and sits at the forefront of the United States response to this pandemic. The goal of this paper is to share the lessons learned by our spine division during a crisis when hospital resources and personnel are stretched thin. Such experiences include management of elective and emergent cases, outpatient clinics, physician redeployment and general health and wellness. As peak infections spread across the United States, we hope this article will serve as a resource for other spine departments on how to manage patient care and healthcare worker deployment during the COVID-19 crisis.


title: Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy

text: Abstract This paper investigates the correlation between the high level of coronavirus SARS-CoV-2 infection accelerated transmission and lethality, and surface air pollution in Milan metropolitan area, Lombardy region in Italy. For January–April 2020 period, time series of daily average inhalable gaseous pollutants ozone (O3) and nitrogen dioxide (NO2), together climate variables (air temperature, relative humidity, wind speed, precipitation rate, atmospheric pressure field and Planetary Boundary Layer) were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces or direct human-to-human personal contacts, it seems that high levels of urban air pollution, and climate conditions have a significant impact on SARS-CoV-2 diffusion. Exhibited positive correlations of ambient ozone levels and negative correlations of NO2 with the increased rates of COVID-19 infections (Total number, Daily New positive and Total Deaths cases), can be attributed to airborne bioaerosols distribution. The results show positive correlation of daily averaged O3 with air temperature and inversely correlations with relative humidity and precipitation rates. Viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein, which allows coronavirus attachment on ambient air pollutants. At this moment it is not clear if through airborne diffusion, in the presence of outdoor and indoor aerosols, this protein “spike” of the new COVID-19 is involved in the infectious agent transmission from a reservoir to a susceptible host during the highest nosocomial outbreak in some agglomerated industrialized urban areas like Milan is. Also, in spite of collected data for cold season (winter-early spring) period, when usually ozone levels have lower values than in summer, the findings of this study support possibility as O3 can acts as a COVID-19 virus incubator. Being a novel pandemic coronavirus version, it might be ongoing during summer conditions associated with higher air temperatures, low relative humidity and precipitation levels.


title: Grand Challenges in Migration Biology

text: Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the “grand challenges” in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks ‘big questions’ such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.


title: Influenza A(H1N1)pdm09 Virus Infection in Giant Pandas, China

text: We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.


title: Periurban outbreaks of bovine calf scours in Northern India caused by Cryptosporidium in association with other enteropathogens

text: Bovine calf scours reported to be caused by multiple aetiologies resulting in heavy mortality in unweaned calves and huge economic loss to the dairy farmers. Among these, cryptosporidiosis is an emerging waterborne zoonoses and one of the important causes of neonatal calf diarrhoea. Poor immune response coupled with primary cryptosporidial infections predispose neonatal calves to multiple secondary infections resulting in their deaths. In the present study, faecal samples from 100 diarrhoeic calves randomly picked up out of 17 outbreaks of bovine calf diarrhoea in periurban Ludhiana, Punjab in Northern India were subjected to conventional (microscopy, modified Zeihl–Neelsen (mZN) staining) and immunological and molecular techniques (faecal antigen capture ELISA and PCR) for detection of primary Cryptosporidium parvum infection as well as other frequently reported concurrent pathogens, viz. rotavirus and coronavirus, Salmonella spp., Escherichia coli, Clostridium perfringens and Eimeria spp. The faecal antigen capture ELISA and PCR revealed 35% prevalence of C. parvum in contrast to 25% by mZN staining with a relatively higher prevalence (66·7%) in younger (8–14-day-old) calves. The detection rate of the other enteropathogens associated with C. parvum was 45·71% for C. perfringens followed by Salmonella spp (40·0%), rotavirus (36·0%), coronavirus (16·0%), E. coli (12·0%) and Eimeria spp (4·0%) The sensitivity for detection of C. parvum by ELISA and mZN staining in comparison to PCR was 97·14% and 72·72%, respectively. An important finding of the study was that C. parvum alone was found in only 10% of the diarrhoeic faecal samples, whereas, majority of the samples (90%) showed mixed infections ranging from a combination of two to five agents. This is the first documentary proof of C. parvum and associated pathogens responsible for severe periurban outbreaks of bovine calf diarrhoea culminating in heavy mortality from Northern India.


The utility of ultrasound extends beyond interstitial pneumonia assessment in COVID-19 patients


title: Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review

text: Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.


title: First molecular characterization of Sarcocystis neurona causing meningoencephalitis in a domestic cat in Brazil

text: Sarcocystis neurona is the main agent associated with equine protozoal myeloencephalitis (EPM). Apart from horses, S. neurona has been occasionally described causing neurologic disease in several other terrestrial animals as well as mortality in marine mammals. Herein, we describe the clinical, pathological, and molecular findings of a fatal case of S. neurona-associated meningoencephalitis in a domestic cat. The causing agent was analyzed by multilocus genotyping, confirming the presence of S. neurona DNA in the tissue samples of the affected animal. Significant molecular differences were found in relation to S. neurona isolates detected in other regions of the Americas. In addition, the parasite was identical to Sarcocystis sp. identified in opossum sporocysts in Brazil at molecular level, which suggests that transmission of. S. neurona in Brazil might involve variants of the parasite different from those found elsewhere in the Americas. Studies including more samples of S. neurona would be required to test this hypothesis, as well as to assess the impact of this diversity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-019-06570-w) contains supplementary material, which is available to authorized users.


Pregnancy hypertension diagnosis and care in COVID‐19 era and beyond


title: Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates

text: Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events.


title: Consensus Summary Report for CEPI/BC March 12-13, 2020 Meeting: Assessment of Risk of Disease Enhancement with COVID-19 Vaccines

text: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory Syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.


title: Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

text: OBJECTIVE: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. PATIENTS AND METHODS: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. CONCLUSIONS: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.


title: Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice

text: INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.


The Unpreparedness of the Healthcare System for the Management of COVID-19 Pandemic Leading to the Mistreatment of the Elderly: A Newly Emerging Moral Dilemma


title: Baricitinib: A review of pharmacology, safety and emerging clinical experience in COVID‐19

text: A hyperinflammatory response to SARS‐CoV‐2 infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with COVID‐19. Agents that inhibit components of the pro‐inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the pro‐inflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus‐associated kinase (JAK)‐inhibitor that interrupts the signaling of multiple cytokines implicated in COVID‐19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin‐converting‐enzyme‐2 up regulation. However, baricitinib’s immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients’ immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events which is concerning given the proclivity towards a hyper‐coagulable state in COVID‐19 patients. In this article we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety and current progress in COVID‐19 clinical trials.


title: Cash concerns for Canadian scientists

text: Could programme cuts prompt a brain drain?


title: Management and biosecurity practices on pig farms in the Western Highlands of Cameroon (Central Africa)

text: African swine fever (ASF), erysipelas and many other infectious and parasitic diseases have seriously compromised the future of pig industry in the Western Highlands of Cameroon. Since implementation of biosecurity measures (BM) is known to reduce the risk of disease transmission, the objective of this study was to describe the pig farming management system as well as the biosecurity practices on pig farms in the Western Highlands of Cameroon. Therefore, 97 farms were investigated using a face‐to‐face interview‐based questionnaire. Biosecurity practices were divided in three components: isolation, traffic control and sanitation. The results revealed that the majority of farms were extensive (73.22%), farrow‐to‐finish farms (59.79%) and essentially raising crossed‐bred (72.75%). The most practiced BM regarding ‘isolation’ were as follows: maintenance of the minimum distance between farms (56.06%) and dispatching of animals of same age in the same room (97.16%); for ‘traffic control’, the measures included the following: assignment of specific tools and equipment (96.86%) to a specific piggery; concerning ‘sanitation’, daily cleaning (97.06%), as well as using disinfectants (89.13%) were mostly implemented. The measures less implemented for ‘isolation’ included fencing (11.83%), compliance with the all‐in all‐out principle (10.11%), use of specific clothing (6.03%) and quarantine (7.69%); for ‘traffic control’, the less adopted measures comprised visitor hands washed before animal handling (11.65%), respect of linear flow principle (13.52%). Concerning ‘sanitation’, these measures included functional footbath (29.90%), processing of drinking water (27.84%) and cleanout (18.14%). The biosecurity level was low, intermediate and high for 73.71, 21.55 and 4.73% of farms, respectively. This low level suggests that ASF and other diseases are likely to remain endemic. The most important measures of concern and to improve are as follows: not feeding kitchen waste to pigs; keeping other livestock species away from pigs; fencing pig barn; keeping newly arrived animals in quarantine, not exchanging boars; not selling sick animals.


Seasonal Distribution Of Respiratory Viruses In Pediatric Asthma In Trinidad West Indies


title: Legume Lectins: Proteins with Diverse Applications

text: Lectins are a diverse class of proteins distributed extensively in nature. Among these proteins; legume lectins display a variety of interesting features including antimicrobial; insecticidal and antitumor activities. Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets.


title: Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines

text: Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.


title: Correlation between TGF‐β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain‐like protease

text: Severe acute respiratory syndrome (SARS) coronavirus (SARS‐CoV) papain‐like protease (PLpro), a deubiquitinating enzyme, demonstrates inactivation of interferon (IFN) regulatory factor 3 and NF‐κB, reduction of IFN induction, and suppression of type I IFN signaling pathway. This study investigates cytokine expression and proteomic change induced by SARS‐CoV PLpro in human promonocyte cells. PLpro significantly increased TGF‐β1 mRNA expression (greater than fourfold) and protein production (greater than threefold). Proteomic analysis, Western blot, and quantitative real‐time PCR assays indicated PLpro upregulating TGF‐β1‐associated genes: HSP27, protein disulfide isomerase A3 precursor, glial fibrillary acidic protein, vimentin, retinal dehydrogenase 2, and glutathione transferase omega‐1. PLpro‐activated ubiquitin proteasome pathway via upregulation of ubiquitin‐conjugating enzyme E2–25k and proteasome subunit alpha type 5. Proteasome inhibitor MG‐132 significantly reduced expression of TGF‐β1 and vimentin. PLpro upregulated HSP27, linking with activation of p38 MAPK and ERK1/2 signaling. Treatment with SB203580 and U0126 reduced PLpro‐induced expression of TGF‐β1, vimentin, and type I collagen. Results point to SARS‐CoV PLpro triggering TGF‐β1 production via ubiquitin proteasome, p38 MAPK, and ERK1/2‐mediated signaling.


Mitteilungen der DVSE


title: Managing Burns During COVID-19 Outbreak

text: The coronavirus disease pandemic has affected our practice as healthcare professionals. As burn surgeons, we are obliged to provide the best possible care to our patients. However, due to the risk of viral transmission, the goal should be to provide safe care to our patients as well as ensure the safety of the whole team providing burn care. The burn patients are usually debilitated and require a prolonged hospital stay and multiple operative procedures which put them and everyone involved in their care at increased risk of coronavirus infections and transmission. This warrants special caution to the burn team while managing such patients. In this review, we aim to highlight the key considerations for burn care teams while dealing with burn patients during the COVID-19 pandemic.


title: Characterization of two novel ADP ribosylation factors from giant freshwater prawn Macrobrachium rosenbergii and their responses to WSSV challenge

text: ADP-ribosylation factors (Arfs) are small GTP-binding proteins that have an essential function in intracellular trafficking and organelle structure. To date, little information is available on the Arfs in the economically important giant freshwater prawn Macrobrachium rosenbergii and their relationship to viral infection. Here we identified two Arf genes from M. rosenbergii (MrArf1 and MrArf2) for the first time. Phylogenetic analysis showed that MrArf1, together with MjArf1 from shrimp Marsupenaeus japonicus belonged to Class I Arfs. By contrast, MrArf2 didn't not match any of the Arfs classes of I/II/III, although it could be clustered with an Arf protein from M. japonicas called MjArfn, which may represent an analog of the Arf. MrArf1 was ubiquitously expressed in all the examined tissues, with the highest transcription level in the hepatopancreas, whereas MrArf2 was only highly expressed in the hepatopancreas and exhibited very low levels in the heart, stomach, gills and intestine. The expression level of MrArf1 in the gills was down-regulated post 24 h WSSV challenge, and reached the maximal level at 48 h. MrArf1 in the hepatopancreas went up from 24 to 48 h WSSV challenge. MrArf2 transcript in the gill also went down at 24 h and then was upregulated at 48 h WSSV challenge. MrArf2 increased significantly in the hepatopancreas 24 h after infection and then went down at 48 h WSSV challenge. RNAi results showed that knockdown of MrArf1 or MrArf2 could inhibit the expression of the envelope protein gene vp28 of the WSSV. So, it could be speculated that MrArf1 and MrArf2 might play important roles in the innate immune system against WSSV infection.


title: COVID-19 in Yemen: a crisis within crises

text: Yemen is suffering deadly airstrikes and heavy bombardment since March 2015 which has created one of the most severe humanitarian crises worldwide. In this miserable situation, several communicable diseases have massively re-emerged including cholera, diarrhea, dengue, and measles, as a result of weapons used during the years of war according to geospatial patterns of the infected cases. According to the world health organization (WHO), only 51% of health care facilities across the country are fully functional, mainly due to the war. The fragile health system has extremely limited capacity to adopt and implement effective preparedness and response measures to the COVID-19 outbreak. The first and most imperative step to combat COVID-19 in Yemen is ending the devastating war without delay and terminating the land, sea and air blockade imposed by the coalition. International humanitarian organizations should also dedicate a high level joint action to implement a series of well-coordinated measures emphasizing both whole-of-government and whole-of-society approach to protect Yemenis’ right in life and health.


title: Emergence From the Coronavirus Disease 2019 Pandemic and the Care of Chronic Pain: Guidance for the Interventionalist

text: BACKGROUND: The current Coronavirus Disease (COVID-19) pandemic led to a significant disruption in the care of pain from chronic and subacute conditions. The impact of this cessation of pain treatment may have unintended consequences of increased pain, reduced function, increased reliance on opioid medications, and potential increased morbidity, due to the systemic impact of untreated disease burden. This may include decreased mobility, reduction in overall health status, and increase of opioid use with the associated risks. METHODS: The article is the study of the American Society of Pain and Neuroscience (ASPN) COVID-19 task force to evaluate the policies set forth by federal, state, and local agencies to reduce or eliminate elective procedures for those patients with pain from spine, nerve, and joint disease. The impact of these decisions, which were needed to reduce the spread of the pandemic, led to a delay in care for many patients. We hence review an emergence plan to reinitiate this pain-related care. The goal is to outline a path to work with federal, state, and local authorities to combat the spread of the pandemic and minimize the deleterious impact of pain and suffering on our chronic pain patients. RESULTS: The article sets forth a strategy for the interventional pain centers to reemerge from the current pandemic and to set a course for future events. CONCLUSIONS: xxx.


title: Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance

text: Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.


Comment on “Colchicine may not be effective in COVID-19 infection; it may even be harmful?”


Heart Failure in the COVID-19 Pandemic: Where has all New York's congestion gone?


title: Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells

text: Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including β cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells. We demonstrate a cell-type-specific response by autologous immune cells against induced pluripotent stem cell-derived β cells, along with a reduced effect on α cells. This approach represents a path to developing disease models that use patient-derived cells to predict the outcome of an autoimmune response.


title: Cloning and characterization of giant panda (Ailuropoda melanoleuca) IL-18 binding protein

text: Abstract The giant panda (Ailuropoda melanoleuca) is an endangered species. Interleukin-18 (IL-18) plays an important role in the innate and adaptive immune responses by inducing IFN-γ. IL-18 has been implicated in the pathogenesis of various diseases. IL-18 binding protein (IL-18BP) is an intrinsic inhibitor of IL-18 that possesses higher affinity to IL-18. In this study, we cloned and characterized IL-18BP in giant panda (AmIL-18BP) from the spleen. The amino acid sequence of giant panda IL-18BP ORF shared about 65% identities with other species. To evaluate the effects of AmIL-18BP on the immune responses, we expressed the recombinant AmIL-18BP in Escherichia coli BL21 (DE3).The fusing protein PET-AmIL-18BP was purified by nickel affinity column chromatography. The biological function of purified PET-AmIL-18BP was determined on mice splenocyte by qRT-PCR. The results showed that AmIL-18BP was functional and could significantly reduce IFN-γ production in murine splenocytes. These results will facilitate the study of protecting giant panda on etiology and immunology.


title: Antibiotic use for community-acquired pneumonia in neonates and children: WHO evidence review

text: Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises the evidence for the empirical antibiotic treatment of community-acquired pneumonia in neonates and children and puts emphasis on publications since the release of the previous WHO Evidence Summary report published in 2014. Methods A systematic search for systematic reviews and meta-analyses of antibiotic therapy for community-acquired pneumonia was conducted between 1 January 2013 and 10 November 2016. Results The optimal dosing recommendation for amoxicillin remains unclear with limited pharmacological and clinical evidence. There is limited evidence from surveillance to indicate whether amoxicillin or broader spectrum antibiotics (e.g. third-generation cephalosporins) are being used most commonly for paediatric CAP in different WHO regions. Data are lacking on clinical efficacy in the context of pneumococcal, staphylococcal and mycoplasma disease and the relative contributions of varying first-line and step-down options to the selection of such resistance. Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia.


title: Development of a highly sensitive real-time nested RT-PCR assay in a single closed tube for detection of enterovirus 71 in hand, foot, and mouth disease

text: Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease (HFMD). A commercial TaqMan probe-based real-time PCR assay has been widely used for the differential detection of EV71 despite its relatively high cost and failure to detect samples with a low viral load (Ct value > 35). In this study, a highly sensitive real-time nested RT-PCR (RTN RT-PCR) assay in a single closed tube for detection of EV71 in HFMD was developed. The sensitivity and specificity of this assay were evaluated using a reference EV71 stock and a panel of controls consisting of coxsackievirus A16 (CVA16) and common respiratory viruses, respectively. The clinical performance of this assay was evaluated and compared with those of a commercial TaqMan probe-based real-time PCR (qRT-PCR) assay and a traditional two-step nested RT-PCR assay. The limit of detection for the RTN RT-PCR assay was 0.01 TCID(50)/ml, with a Ct value of 38.3, which was the same as that of the traditional two-step nested RT-PCR assay and approximately tenfold lower than that of the qRT-PCR assay. When testing the reference strain EV71, this assay showed favorable detection reproducibility and no obvious cross-reactivity. The testing results of 100 clinical throat swabs from HFMD-suspected patients revealed that 41 samples were positive for EV71 by both RTN RT-PCR and traditional two-step nested RT-PCR assays, whereas only 29 were EV71 positive by qRT-PCR assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-2985-6) contains supplementary material, which is available to authorized users.


title: Is Network Clustering Detectable in Transmission Trees?

text: Networks are often used to model the contact processes that allow pathogens to spread between hosts but it remains unclear which models best describe these networks. One question is whether clustering in networks, roughly defined as the propensity for triangles to form, affects the dynamics of disease spread. We perform a simulation study to see if there is a signal in epidemic transmission trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR) epidemics (with no re-infection) over networks with fixed degree sequences but different levels of clustering and compare trees from networks with the same degree sequence and different clustering levels. We find that the variation of such trees simulated on networks with different levels of clustering is barely greater than those simulated on networks with the same level of clustering, suggesting that clustering can not be detected in transmission data when re-infection does not occur.


title: COVID-19 phenotypes: leading or misleading?

text: Comment to an Editorial where we invite the authors to express with clarity the risks they are referring to and how their argument is furthering the cause of patients and clinicians.


Chapter 83 Clinical Aspects of Bronchial Reactivity and Cell–Virus Interaction


Death in 2000 ways


title: Altered distribution of mucosal NK cells during HIV infection

text: The human gut mucosa is a major site of HIV infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells play an important role in control of HIV infection but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here we show two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (IEL) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective KIR/HLA genotypes. Both IEL and LP NK cells were significantly expanded in immunologic non-responsive (INR) patients, who incompletely recovered CD4+ T cells on HAART. These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut,


title: Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene

text: AIMS: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. METHODS: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. RESULTS: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe–host interactions, the term ‘hygiene hypothesis’ is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. CONCLUSION: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term ‘hygiene hypothesis’ must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease.


title: Cough and viruses in airways disease: Mechanisms

text: Abstract Acute cough is a major symptom of viral respiratory tract infection and causes excessive morbidity in human populations across the world. A wide variety of viruses play a role in the development of cough after acute infection and all of these manifest a similar clinical picture across different age groups. Despite the large disease burden surprisingly little is known about the mechanism of acute cough following viral infection. Both in vitro and in vivo experiments show that increased production of neuropeptides and leukotrienes mediate cough after viral infection, along with altered expression of neural receptors. Increased airway mucus production is also likely to play a significant role. This work is reviewed in this article. Following the recent development of a mouse model for rhinovirus infection and the establishment of experimental models of rhinovirus challenge in human subjects with both asthma and COPD the field is expanding to translate in vitro research into clinical studies and hopefully eventually into clinical practice. Developing a clearer understanding of the mechanisms underlying virus induced cough may lead to more specific and effective therapies.


COVID-19 in MS and NMOSD: A multicentric online national survey in Chile


title: Cymbidium mosaic potexvirus isolate-dependent host movement systems reveal two movement control determinants and the coat protein is the dominant

text: Abstract Little is known about how plant viruses of a single species exhibit different movement behavior in different host species. Two Cymbidium mosaic potexvirus (CymMV) isolates, M1 and M2, were studied. Both can infect Phalaenopsis orchids, but only M1 can systemically infect Nicotiana benthamiana plants. Protoplast inoculation and whole-mount in situ hybridization revealed that both isolates can replicate in N. benthamiana; however, M2 was restricted to the initially infected cells. Genome shuffling between M1 and M2 revealed that two control modes are involved in CymMV host dependent movement. The M1 coat protein (CP) plays a dominant role in controlling CymMV movement between cells, because all chimeric CymMV viruses containing the M1 CP systemically infected N. benthamiana plants. Without the M1 CP, one chimeric virus containing the combination of the M1 triple gene block proteins (TGBps), the M2 5′ RNA (1–4333), and the M2 CP effectively moved in N. benthamiana plants. Further complementation analysis revealed that M1 TGBp1 and TGBp3 are co-required to complement the movement of the chimeric viruses in N. benthamiana. The amino acids within the CP, TGBp1 and TGBp3 which are required or important for CymMV M2 movement in N. benthamiana plants were mapped. The required amino acids within the CP map to the predicted RNA binding domain. RNA–protein binding assays revealed that M1 CP has higher RNA binding affinity than does M2 CP. Yeast two-hybrid assays to detect all possible interactions of M1 TGBps and CP, and only TGBp1 and CP self-interactions were observed.


title: Effect of weaning status on animal performance and meat quality of Rubia Gallega calves

text: The effect of weaning calves at different ages (NW = not weaned, W5 = 5.5 months old and W2 = weaned after being born and then fed with natural Holstein Friesian milk until 2 months old), on animal performance and carcass and Longissimus thoracis muscle quality, was studied in 36 eight month-old Rubia Gallega calves. Feed ingestions, weight gains, slaughter (SW) and carcass weights (CW), carcass conformation and fat scores, and meat characteristics (24 hours postmortem): colour, pH, water holding capacity, chemical composition and texture (Warner Bratzler (WB) test, sensory panel), were studied. NW calves showed the highest SW and CW (P < 0.001). Yellowness (b*), redness (a*) and chroma (C*) were higher in NW than W2 calves (P < 0.05). Shear firmness was higher in W2 than in NW and W5 veal. W2 veal was less elastic (P < 0.05), tender (P < 0.05) and juicy (P < 0.01) than NW and W5 veal.


title: Public health initiatives from hospitalized patients with COVID-19, China

text: Abstract Background Since December 2019, when it first occurred in Wuhan, China, coronavirus disease 2019 (COVID-19) has spread rapidly worldwide via human-to-human transmission. We aimed to describe the epidemiological and demographic features of COVID-19 outside Wuhan. Methods A single-center case series of 136 consecutive (from January 16 to February 17, 2020) patients with confirmed COVID-19 hospitalized in The First People's Hospital of Jingzhou, China, was retrospectively analyzed. Outcomes were followed up until February 19, 2020. Results Of the 136 patients (median age, 49 years; interquartile range [IQR], 33–63 years; range, 0.3–83 years), 91 (67%) had been to Wuhan or contacted persons from Wuhan. Forty-five (33.1%) were familial clusters. The median incubation period was 6 days (IQR: 4–11 days). All children had an exact exposure history, family members with COVID-19, and “Mild/Moderate” symptoms at admission. Among the 64 elderly patients, 14 (21.9%) had no exposure history, and 43 (67.2%) had a chronic illness. All 11 (8.1%) “Severe/Very severe” illness at onset cases and 5 (3.7%) fatal cases were elderly patients. The duration from symptom onset to admission was positively correlated with the duration from symptom onset to endpoint. Overall, patients with a longer incubation period had more severe outcomes. Conclusion As high-risk susceptible groups, strong protection should be implemented for children and the elderly. Universal screening should be performed for people with a clear exposure history, even lacking apparent symptoms. Given the rapid progression of COVID-19, people should be admitted quickly following symptom onset.


Urolithiasis due to Hereditary Xanthinuria Type II: A Long-term Follow-up report


Do Matrix Metalloproteases mediate the SARS-CoV-2-related damage to the Central Nervous System?


title: Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT findings.

text: OBJECTIVE The purpose of this study was to describe the chest CT findings in seven patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. CONCLUSION The most common CT finding in hospitalized patients with MERS-CoV infection is that of bilateral predominantly subpleural and basilar airspace changes, with more extensive ground-glass opacities than consolidation. The subpleural and peribronchovascular predilection of the abnormalities is suggestive of an organizing pneumonia pattern.


title: Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host

text: Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.


title: Rhinovirus and Innate Immune Function of Airway Epithelium

text: Airway epithelial cells, which lines the respiratory mucosa is in direct contact with the environment. Airway epithelial cells are the primary target for rhinovirus and other inhaled pathogens. In response to rhinovirus infection, airway epithelial cells mount both pro-inflammatory responses and antiviral innate immune responses to clear the virus efficiently. Some of the antiviral responses include the expression of IFNs, endoplasmic reticulum stress induced unfolded protein response and autophagy. Airway epithelial cells also recruits other innate immune cells to establish antiviral state and resolve the inflammation in the lungs. In patients with chronic lung disease, these responses may be either defective or induced in excess leading to deficient clearing of virus and sustained inflammation. In this review, we will discuss the mechanisms underlying antiviral innate immunity and the dysregulation of some of these mechanisms in patients with chronic lung diseases.


title: Viral infections associated with Kawasaki disease

text: Background/Purpose Kawasaki disease (KD) is a disease of unknown cause. To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. Methods We enrolled 226 children with KD and 226 age- and sex-matched healthy children from February 2004 to March 2010. Throat and nasopharyngeal swabs were taken for both viral isolation and polymerase chain reaction (PCR) for various viruses. Results The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003). Conclusion We found that some common respiratory viruses, such as adenoviruses, enteroviruses, rhinoviruses, and coronaviruses, were associated with KD cases.