title: Willingness to accept a future influenza A(H7N9) vaccine in Beijing, China

text: Abstract Background The present study aimed to estimate residents’ willingness to accept a future H7N9 vaccine and its determinants in the general adult population in Beijing, China. Methods We conducted a multi-stage sampling, cross-sectional survey using self-administered anonymous questionnaires from May to June, in 2014. The main outcome variable was residents’ willingness to accept a future H7N9 vaccine. Logistic regression was used to identify the predictors of vaccination willingness. Results Of the 7264 eligible participants, 14.5% of Beijing residents reported that they had not heard of H7N9. Among those who had heard of H7N9, 59.5% of the general adult population would be willing to accept a future H7N9 vaccine, and approximately half of them reported ‘I am afraid of being infected by H7N9’ and ‘H7N9 vaccine can prevent infections’, and 28.1% reported ‘my daily life is affected by H7N9’. The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18–29 years: OR = 1.52, 95% CI: 1.17–1.97; aged 30–39 years: OR = 1.39, 95% CI: 1.08–1.78), being farmers (OR = 1.61; 95% CI: 1.32–1.96), being unemployed people (OR = 1.36; 95% CI: 1.04–1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89–2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03–1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15–1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73–3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13–1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07–2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92–2.66). Conclusions A great number of Beijing residents had doubts about the vaccine’s effectiveness and were not concerned about disease risk, which were the factors affecting willingness to be vaccinated. Targeted education programs on disease risk as well as vaccine’s effectiveness are needed to improve the willingness of vaccination for potential H7N9 pandemic preparedness.


title: Modeling mitigation of influenza epidemics by baloxavir

text: Influenza viruses annually kill 290,000–650,000 people worldwide. Antivirals can reduce death tolls. Baloxavir, the recently approved influenza antiviral, inhibits initiation of viral mRNA synthesis, whereas oseltamivir, an older drug, inhibits release of virus progeny. Baloxavir blocks virus replication more rapidly and completely than oseltamivir, reducing the duration of infectiousness. Hence, early baloxavir treatment may indirectly prevent transmission. Here, we estimate impacts of ramping up and accelerating baloxavir treatment on population-level incidence using a new model that links viral load dynamics from clinical trial data to between-host transmission. We estimate that ~22 million infections and >6,000 deaths would have been averted in the 2017–2018 epidemic season by administering baloxavir to 30% of infected cases within 48 h after symptom onset. Treatment within 24 h would almost double the impact. Consequently, scaling up early baloxavir treatment would substantially reduce influenza morbidity and mortality every year. The development of antivirals against the SARS-CoV2 virus that function like baloxavir might similarly curtail transmission and save lives.


title: A home hospitalization system based on the Internet of things, Fog computing and cloud computing

text: In recent years, the world has witnessed a significant increase in the number of elderly who often suffer from chronic diseases, and has witnessed in recent months a major spread of the new coronavirus (COVID-19), which has led to thousands of deaths, especially among the elderly and people who suffer from chronic diseases. Coronavirus has also caused many problems in hospitals, where these are no longer able to accommodate a large number of patients. This virus has also begun to spread between medical and paramedical teams, and this causes a major risk to the health of patients staying in hospitals. To reduce the spread of the virus and maintain the health of patients who need a hospital stay, home hospitalization is one of the best possible solutions. This paper proposes a home hospitalization system based on the Internet of Things (IoT), Fog computing, and Cloud computing, which are among the most important technologies that have contributed to the development of the healthcare sector in a significant way. These systems allow patients to recover and receive treatment in their homes and among their families, where patient health and the hospitalization room environmental state are monitored, to enable doctors to follow the hospitalization process and make recommendations to patients and their supervisors, through monitoring units and mobile applications developed for this purpose. The results of evaluation have shown great acceptance of this system by patients and doctors alike.


title: MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet

text: BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.


Investigations continue as SARS claims more lives


title: Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

text: Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.


Recommendations for Physical Inactivity and Sedentary Behavior During the Coronavirus Disease (COVID-19) Pandemic


title: Impact of the COVID-19 Pandemic on the Urologist’s clinical practice in Brazil: a management guideline proposal for low- and middle-income countries during the crisis period

text: This letter to the Editor aims to provide suggestions and recommendations for the management of urological conditions in times of COVID-19 crisis in Brazil and other low- and middle-income countries. It is important to highlight that one of the main characteristics of this pandemic is the oversaturation of the health system capacity, mostly due to a high demand for personal protective equipment (PPE), Hospital/ICU beds, as well as ventilators. In places with limited resources and where the health care systems are already saturated, such consideration is even more worrisome. Therefore, most worldwide authorities are recommending to avoid, as much as possible, patient’s elective visits to hospitals, as well as a judicious use of the operating room in order to mitigate the strain put on the health system. While efforts should be directed to the care of COVID-19 patients, other conditions (especially urgencies and oncological cases) must continue to be assisted. Thus, through a panel of experts, we have prepared a practical guide for urologists based on the recommendations from the main Urologic Associations, as well as data from the literature to support the suggested management. We will try to follow the standard guideline recommendations from the American Urological Association (AUA) and European Association of Urology (EAU), with the aim of pursuing the best outcomes possible. However, some recommendations were based on the consensus of the panel, taking into consideration the reality of developing countries and the unprecedented situation caused by the COVID-19 crisis.


Handling Children in COVID Wards: A Narrative Experience and Suggestions for Providing Psychological Support


title: Solution structure of the X4 protein coded by the SARS related coronavirus reveals an immunoglobulin like fold and suggests a binding activity to integrin I domains

text: The SARS related Coronavirus genome contains a variety of novel accessory genes. One of these, called ORF7a or ORF8, code for a protein, known as 7a, U122 or X4. We set out to determine the three-dimensional structure of the soluble ectodomain of this type-I transmembrane protein by nuclear magnetic resonance spectroscopy. The fold of the protein is the first member of a further variation of the immunoglobulin like beta-sandwich fold. Because X4 does not reveal significant sequence homologies to proteins in the data bases, we carried out a structure based similarity search for proteins with known function. High structural similarity to Dl domains of ICAM-1 and ICAM-2, and common features in amino acid sequence between X4 and ICAM-1, suggest X4 to possess binding activity for the [Formula: see text] integrin I domain of LFA-1. Further, based on this structure based prediction, potential functions of X4 in virus replication and pathogenesis are discussed.


title: The basic principles of migration health: Population mobility and gaps in disease prevalence

text: Currently, migrants and other mobile individuals, such as migrant workers and asylum seekers, are an expanding global population of growing social, demographic and political importance. Disparities often exist between a migrant population's place of origin and its destination, particularly with relation to health determinants. The effects of those disparities can be observed at both individual and population levels. Migration across health and disease disparities influences the epidemiology of certain diseases globally and in nations receiving migrants. While specific disease-based outcomes may vary between migrant group and location, general epidemiological principles may be applied to any situation where numbers of individuals move between differences in disease prevalence. Traditionally, migration health activities have been designed for national application and lack an integrated international perspective. Present and future health challenges related to migration may be more effectively addressed through collaborative global undertakings. This paper reviews the epidemiological relationships resulting from health disparities bridged by migration and describes the growing role of migration and population mobility in global disease epidemiology. The implications for national and international health policy and program planning are presented.


title: The global health law trilogy: towards a safer, healthier, and fairer world

text: Summary Global health advocates often turn to medicine and science for solutions to enduring health risks, but law is also a powerful tool. No state acting alone can ward off health threats that span borders, requiring international solutions. A trilogy of global health law—the Framework Convention on Tobacco Control, International Health Regulations (2005), and Pandemic Influenza Preparedness Framework—strives for a safer, healthier, and fairer world. Yet, these international agreements are not well understood, and contain gaps in scope and enforceability. Moreover, major health concerns remain largely unregulated at the international level, such as non-communicable diseases, mental health, and injuries. Here, we offer reforms for this global health law trilogy.


title: The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

text: BACKGROUND: Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs). Six E2 epitopes (E2(c,d,e,f,g,h)) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182–207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs) with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115–119. Using a 9 Å resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration of a cocktail of F5n and Hy4 IgGs, which bind to different E2 epitopes, could provide enhanced prophylaxis or immunotherapy for VEEV, while reducing the possibility of generating possibly harmful virus neutralization-escape variants in vivo.


title: A multiplex reverse transcription PCR and automated electronic microarray assay for detection and differentiation of seven viruses affecting swine

text: Microarray technology can be useful for pathogen detection as it allows simultaneous interrogation of the presence or absence of a large number of genetic signatures. However, most microarray assays are labour‐intensive and time‐consuming to perform. This study describes the development and initial evaluation of a multiplex reverse transcription (RT)‐PCR and novel accompanying automated electronic microarray assay for simultaneous detection and differentiation of seven important viruses that affect swine (foot‐and‐mouth disease virus [FMDV], swine vesicular disease virus [SVDV], vesicular exanthema of swine virus [VESV], African swine fever virus [ASFV], classical swine fever virus [CSFV], porcine respiratory and reproductive syndrome virus [PRRSV] and porcine circovirus type 2 [PCV2]). The novel electronic microarray assay utilizes a single, user‐friendly instrument that integrates and automates capture probe printing, hybridization, washing and reporting on a disposable electronic microarray cartridge with 400 features. This assay accurately detected and identified a total of 68 isolates of the seven targeted virus species including 23 samples of FMDV, representing all seven serotypes, and 10 CSFV strains, representing all three genotypes. The assay successfully detected viruses in clinical samples from the field, experimentally infected animals (as early as 1 day post‐infection (dpi) for FMDV and SVDV, 4 dpi for ASFV, 5 dpi for CSFV), as well as in biological material that were spiked with target viruses. The limit of detection was 10 copies/μl for ASFV, PCV2 and PRRSV, 100 copies/μl for SVDV, CSFV, VESV and 1,000 copies/μl for FMDV. The electronic microarray component had reduced analytical sensitivity for several of the target viruses when compared with the multiplex RT‐PCR. The integration of capture probe printing allows custom onsite array printing as needed, while electrophoretically driven hybridization generates results faster than conventional microarrays that rely on passive hybridization. With further refinement, this novel, rapid, highly automated microarray technology has potential applications in multipathogen surveillance of livestock diseases.


title: Cysteine cathepsins: From structure, function and regulation to new frontiers

text: Abstract It is more than 50years since the lysosome was discovered. Since then its hydrolytic machinery, including proteases and other hydrolases, has been fairly well identified and characterized. Among these are the cysteine cathepsins, members of the family of papain-like cysteine proteases. They have unique reactive-site properties and an uneven tissue-specific expression pattern. In living organisms their activity is a delicate balance of expression, targeting, zymogen activation, inhibition by protein inhibitors and degradation. The specificity of their substrate binding sites, small-molecule inhibitor repertoire and crystal structures are providing new tools for research and development. Their unique reactive-site properties have made it possible to confine the targets simply by the use of appropriate reactive groups. The epoxysuccinyls still dominate the field, but now nitriles seem to be the most appropriate “warhead”. The view of cysteine cathepsins as lysosomal proteases is changing as there is now clear evidence of their localization in other cellular compartments. Besides being involved in protein turnover, they build an important part of the endosomal antigen presentation. Together with the growing number of non-endosomal roles of cysteine cathepsins is growing also the knowledge of their involvement in diseases such as cancer and rheumatoid arthritis, among others. Finally, cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes. The current challenge is to identify their endogenous substrates, in order to gain an insight into the mechanisms of substrate degradation and processing. In this review, some of the remarkable advances that have taken place in the past decade are presented. This article is part of a Special Issue entitled: Proteolysis 50years after the discovery of lysosome.


title: Undernutrition, obesity and governance: a unified framework for upholding the right to food

text: This paper addresses the need for conceptual and analytic clarity on nutrition governance, an essential underpinning of more effective approaches for undernutrition, the ‘single greatest constraint to global development’ and obesity, which already accounts for 4% of the world’s disease burden and is growing rapidly. The governance of nutrition, which is essential to designing and implementing policies to realise the right to food, is among the most important and most defining duties of society. But research and action on nutrition governance are hampered by the absence of conceptual rigour, even as the continuing very high burden of undernutrition and the rapid rise in obesity highlight the need for such structures. The breadth of nutrition itself suggests that governance is both needed and sure to be complicated. This analysis explores the reasons attention has come to governance in development policy making, and why it has focused on nutrition governance in particular. It then assesses how the concept of nutrition governance has been used, finding that it has become increasingly prominent in scholarship on poor nutritional outcomes, but remains weakly specified and is invoked by different authors to mean different things. Undernutrition analysts have stressed coordination problems and structural issues related to the general functioning of government. Those studying obesity have emphasised international trade policies, regulatory issues and corporate behaviour. This paper argues that the lack of a clear, operational definition of governance is a serious obstacle to conceptualising and solving major problems in nutrition. To address this need, it develops a unified definition of nutrition governance consisting of three principles: accountability, participation and responsiveness. These are justified with reference to the social contract that defines modern nations and identifies citizens as the ultimate source of national power and legitimacy. A unified framework is then employed to explore solutions to nutrition governance problems.


title: Braess's Paradox in Epidemic Game: Better Condition Results in Less Payoff

text: Facing the threats of infectious diseases, we take various actions to protect ourselves, but few studies considered an evolving system with competing strategies. In view of that, we propose an evolutionary epidemic model coupled with human behaviors, where individuals have three strategies: vaccination, self-protection and laissez faire, and could adjust their strategies according to their neighbors' strategies and payoffs at the beginning of each new season of epidemic spreading. We found a counter-intuitive phenomenon analogous to the well-known Braess's Paradox, namely a better condition may lead to worse performance. Specifically speaking, increasing the successful rate of self-protection does not necessarily reduce the epidemic size or improve the system payoff. The range and degree of the Braess's Paradox are sensitive to both the parameters characterizing the epidemic spreading and the strategy payoff, while the existence of the Braess's Paradox is insensitive to the network topologies. This phenomenon can be well explained by a mean-field approximation. Our study demonstrates an important fact that a better condition for individuals may yield a worse outcome for the society.


title: Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses

text: Abstract Fast-track Diagnostics respiratory pathogens (FTDRP) multiplex real-time RT-PCR assay was compared with in-house singleplex real-time RT-PCR assays for detection of 16 common respiratory viruses. The FTDRP assay correctly identified 26 diverse respiratory virus strains, 35 of 41 (85%) external quality assessment samples spiked with cultured virus and 232 of 263 (88%) archived respiratory specimens that tested positive for respiratory viruses by in-house assays. Of 308 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 270 (87.7%) and 265 (86%) were positive by FTDRP and in-house assays for one or more viruses, respectively, with combined test results showing good concordance (K =0.812, 95% CI=0.786–0.838). Individual FTDRP assays for adenovirus, respiratory syncytial virus and rhinovirus showed the lowest comparative sensitivities with in-house assays, with most discrepancies occurring with specimens containing low virus loads and failed to detect some rhinovirus strains, even when abundant. The FTDRP enterovirus and human bocavirus assays appeared to be more sensitive than the in-house assays with some specimens. With the exceptions noted above, most FTDRP assays performed comparably with in-house assays for most viruses while offering enhanced throughput and easy integration by laboratories using conventional real-time PCR instrumentation.


Challenges and Responses to Podiatric Medical Education and Patient Care Requirements at the New York College of Podiatric Medicine During the COVID-19 Pandemic


title: Public Health Law and Science in the Community Mitigation Strategy for Covid-19

text: In a crisis like the Covid-19 pandemic, the role of judges is first and foremost to adjudicate urgent requests for temporary restraining orders and preliminary injunctions. This means that judges hearing challenges to bans on gatherings, orders to close gun shops, orders to halt abortion care, and detention of civil immigration detainees in crowded and unsanitary conditions are issuing orders based on the parties’ pleadings alone. There is no time—yet—for the discovery, expert testimony, or amicus briefs from professional groups that typically inform assessments of science by judges. This essay examines the role public health science is likely to play in the coming months as judges field challenges to mandatory orders adopted as part of the community mitigation the Covid-19 pandemic. It identifies voluntary guidelines from international and federal health agencies as a resource judges rely on heavily in reviewing emergency communicable disease control orders and argues that transparency of and accountability for guidelines should therefore be held to a higher bar than their voluntary status might otherwise suggest.


title: Evaluating the Adequacy of Molecular Clock Models Using Posterior Predictive Simulations

text: Molecular clock models are commonly used to estimate evolutionary rates and timescales from nucleotide sequences. The goal of these models is to account for rate variation among lineages, such that they are assumed to be adequate descriptions of the processes that generated the data. A common approach for selecting a clock model for a data set of interest is to examine a set of candidates and to select the model that provides the best statistical fit. However, this can lead to unreliable estimates if all the candidate models are actually inadequate. For this reason, a method of evaluating absolute model performance is critical. We describe a method that uses posterior predictive simulations to assess the adequacy of clock models. We test the power of this approach using simulated data and find that the method is sensitive to bias in the estimates of branch lengths, which tends to occur when using underparameterized clock models. We also compare the performance of the multinomial test statistic, originally developed to assess the adequacy of substitution models, but find that it has low power in identifying the adequacy of clock models. We illustrate the performance of our method using empirical data sets from coronaviruses, simian immunodeficiency virus, killer whales, and marine turtles. Our results indicate that methods of investigating model adequacy, including the one proposed here, should be routinely used in combination with traditional model selection in evolutionary studies. This will reveal whether a broader range of clock models to be considered in phylogenetic analysis.


title: Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics?

text: OBJECTIVES: Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics. METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI. RESULTS: Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51. CONCLUSIONS: ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities.


title: Paediatric gastroenteritis in the eastern Malaysian state of Sarawak: an epidemiological and clinical study

text: Abstract Over a period of 2 months, 35 of 69 (51%) cases of juvenile diarrhoea studied in eastern Malaysia were associated with rotavirus excretion; rotavirus associated diarrhoea occurred most commonly in the 6–24 month age group. Polyacrylamide gel electrophoresis (PAGE) of genome ribonucleic acid showed that only 4 rotavirus electropherotypes could be detected. Of those, 2 predominated and 2 were detected only once each; one of these may have been a reassortaient of the two predominant electropherotypes. Analysis of the clinical features of patients excreting rotavirus subgroup 1 or 2, determined by PAGE, demonstrated that rotavirus subgroup 1 was associated with more hypotonic dehydration and need for intravenous therapy: lethargy was significantly more common among those excreting rotavirus subgroup 2.


Inconveniences due to the use of face masks during the COVID‐19 pandemic: a survey study of 876 young people


title: Studying Public Perception about Vaccination: A Sentiment Analysis of Tweets

text: Text analysis has been used by scholars to research attitudes toward vaccination and is particularly timely due to the rise of medical misinformation via social media. This study uses a sample of 9581 vaccine-related tweets in the period 1 January 2019 to 5 April 2019. The time period is of the essence because during this time, a measles outbreak was prevalent throughout the United States and a public debate was raging. Sentiment analysis is applied to the sample, clustering the data into topics using the term frequency–inverse document frequency (TF-IDF) technique. The analyses suggest that most (about 77%) of the tweets focused on the search for new/better vaccines for diseases such as the Ebola virus, human papillomavirus (HPV), and the flu. Of the remainder, about half concerned the recent measles outbreak in the United States, and about half were part of ongoing debates between supporters and opponents of vaccination against measles in particular. While these numbers currently suggest a relatively small role for vaccine misinformation, the concept of herd immunity puts that role in context. Nevertheless, going forward, health experts should consider the potential for the increasing spread of falsehoods that may get firmly entrenched in the public mind.


title: Large‐scale National Screening for COVID‐19 in China

text: Faced with the new challenges in the pandemic control, imported COVID‐19 infections and asymptomatic infection, Chinese authorities have implemented new intervention measures‐‐‐‐ national large‐scale nucleic acid testing. This article summarizes the population who needs the nucleic acid testing, analyzes the current data of daily COVID‐19 tests per thousand people, concludes the timeline of coronavirus testing and suggests what needs to be done to facilitate the government large‐scale screening measures. This article is protected by copyright. All rights reserved.


title: “We’re staying at home”. Association of self-perceptions of aging, personal and family resources and loneliness with psychological distress during the lock-down period of COVID-19

text: OBJECTIVES: Families are going through a very stressful time because of the COVID-19 outbreak, with age being a risk factor for this illness. Negative self-perceptions of aging, among other personal and relational variables may be associated with loneliness and distress caused by the pandemic crisis. METHOD: Participants are 1310 Spanish people (age range: 18-88 years) during a lock-down period at home. In addition to specific questions about risk for COVID-19, self-perceptions of aging, family and personal resources, loneliness and psychological distress were measured. Hierarchical regression analyses were done for assessing the correlates of loneliness and psychological distress. RESULTS: The measured variables allow for an explanation of 48% and 33% of the variance of distress and loneliness, respectively. Being female, younger, having negative self-perceptions about aging, more time exposed to news about COVID-19, more contact with relatives different to those that co-reside, fewer positive emotions, less perceived self-efficacy, lower quality of sleep, higher expressed emotion and higher loneliness were associated with higher distress. Being female, younger, having negative self-perceptions about aging, more time exposed to news about COVID-19, lower contact with relatives, higher self-perception as a burden, fewer positive emotions, lower resources for entertaining oneself, lower quality of sleep and higher expressed emotion were associated with higher loneliness.


title: How to Guarantee the Best of Care to Patients with Cancer During the COVID‐19 Epidemic: The Italian Experience

text: Italy and the rest of the world are experiencing an outbreak of a novel beta‐coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In this context, in Italy, we reorganized the National Health System and prioritized the clinical cancer care scenario, balancing risk of SARS‐CoV‐2 transmission versus the magnitude of clinical benefit deriving from a specific therapeutic approach. As initial actions, we recommended that routine screening be suspended and that patients with early and advanced cancer be treated as outpatients as much as possible and at the nearest medical center. Patients who need to be hospitalized for cancer treatment were protected from potential SARS‐CoV‐2 infection by creating a dedicated diagnostic and therapeutic internal pathway for cancer treatment. We implemented reorganization of the hospital networks, based on a hub‐and‐spoke design. Stronger personal protection was made available for patients with cancer. Because of the extreme burden created by COVID‐19, antitumor treatment was initiated only after considering patient performance status, comorbidities, biology of disease, and the likely impact of treatment on outcome. Treatment strategies were discussed in the context of a multidisciplinary tumor board. Treatment decision making balanced risk and benefits of treatment in the context of the specific pandemic level, on a case‐by‐case basis.


title: Critical overview on the application of sensors and biosensors for clinical analysis

text: Abstract Sensors and biosensors have been increasingly used for clinical analysis due to their miniaturization and portability, allowing the construction of diagnostic devices for point-of-care testing. This paper presents an up-to-date overview and comparison of the analytical performance of sensors and biosensors recently used in clinical analysis. This includes cancer and cardiac biomarkers, hormones, biomolecules, neurotransmitters, bacteria, virus and cancer cells, along with related significant advances since 2011. Some methods of enhancing the analytical performance of sensors and biosensors through their figures of merit are also discussed.


title: Angiotensin‐(1‐7) and Obesity: Role on cardiorespiratory fitness and COVID‐19 implications

text: We have read with interest the recent review by Zbinden‐Foncea et.al., suggesting that high levels of cardiorespiratory fitness induced by prior exercise training may confer some innate immune‐protection against Covid‐19 by attenuating the “cytokine storm syndrome” by modulating angiotensin‐converting enzyme 2 (ACE2) effects. However, it is important to highlight that the benefic effects of physical exercise also involves the Ang‐(1‐7)/Mas axis activation.


title: Cloning and characterization of a putative mouse acetyl-CoA transporter cDNA

text: Abstract A mouse acetyl-CoA transporter (Acatn) cDNA was isolated by PCR cloning. Mouse Acatn exhibited 92% homology with human sequence on the basis of amino-acid sequence. The predicted gene product of Acatn is a 61kDa hydrophobic protein with six to 10 transmembrane domains. Transfection of mouse Acatn cDNA into HeLa/GT3+ cells resulted in significant increase in the amount of 9-O-acetylated gangliosides, suggesting that Acatn does play an important role in the acetylation of gangliosides. Northern blot analysis of Acatn mRNA suggested that transcript of Acatn is widely distributed in various adult tissues. Expression of Acatn was found to be developmentally regulated, with high expression levels during early embryonic stages, and then there was a subsequent decrease in expression levels in the later embryonic stages.


title: Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells

text: Abstract The recent Zika virus (ZIKV) outbreak, which mainly affected Brazil and neighbouring states, demonstrated the paucity of information concerning the epidemiology of several flaviruses, but also highlighted the lack of available agents with which to treat such emerging diseases. Here, we show that heparin, a widely used anticoagulant, while exerting a modest inhibitory effect on Zika Virus replication, fully prevents virus-induced cell death of human neural progenitor cells (NPCs).


title: Mechanistic Insight into Long Noncoding RNAs and the Placenta

text: Long non-coding RNAs (lncRNAs) are classified as RNAs greater than 200 nucleotides in length that do not produce a protein product. lncRNAs are expressed with cellular and temporal specificity and have been shown to play a role in many cellular events, including the regulation of gene expression, post-transcriptional modifications and epigenetic modifications. Since lncRNAs were first discovered, there has been increasing evidence that they play important roles in the development and function of most organs, including the placenta. The placenta is an essential transient organ that facilitates communication and nutrient exchange between the mother and foetus. The placenta is of foetal origin and begins to form shortly after the embryo implants into the uterine wall. The placenta relies heavily on the successful differentiation and function of trophoblast cells, including invasion as well as the formation of the maternal/foetal interface. Here, we review the current literature surrounding the involvement of lncRNAs in the development and function of trophoblasts and the human placenta.


title: Predictive factors of mortality in patients treated with tocilizumab for acute respiratory distress syndrome related to coronavirus disease 2019 (COVID-19)

text: COVID-19 patients (n=34) suffering from ARDS were treated with tocilizumab (TCZ). Outcome was classified in two groups: “Death” and “Recovery”. Predictive factors of mortality were studied. Mean age was 75.3, mean oxygen (O(2)) requirements 10.4 l/min. At baseline, all patients had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer and liver enzymes). 24 patients (70.5%) recovered after TCZ therapy and 10 died (29.5%). Deceased subjects differed from patients in whom treatment was effective with regard to more pronounced lymphopenia (0.6 vs 1.0 G/l; p=0.037), lower platelet number (156 vs 314 G/l; p=0.0001), lower fibrinogen serum level (0.6 vs 1.0 G/l; p=0.03), higher aspartate-amino-transferase (108 vs 57 UI/l; p=0.05) and greater O(2) requirements (11 vs 8 l/min; p= 0.003).


title: Survey Says: “COVID-19 Lockdown Hits Young Faculty and Clinical Trials”

text: COVID-19 has severely impacted laboratory research. Analysis of the International Society for Stem Cell Research (ISSCR) member survey has highlighted a particular impact on clinical trials and early-career investigators. The stem cell community needs to support young researchers and ensure that stem cell medicine does not lose its momentum.


title: The future of bacteriophage biology

text: After an illustrious history as one of the primary tools that established the foundations of molecular biology, bacteriophage research is now undergoing a renaissance in which the primary focus is on the phages themselves rather than the molecular mechanisms that they explain. Studies of the evolution of phages and their role in natural ecosystems are flourishing. Practical questions, such as how to use phages to combat human diseases that are caused by bacteria, how to eradicate phage pests in the food industry and what role they have in the causation of human diseases, are receiving increased attention. Phages are also useful in the deeper exploration of basic molecular and biophysical questions.


title: Diagnostic accuracy of the FebriDx host response point-of-care test in patients hospitalised with suspected COVID-19

text: INTRODUCTION: Management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and so rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 minutes, but its accuracy for the identification of COVID-19 is unknown. METHODS: We performed a real-world diagnostic accuracy study of FebriDx in hospitalised patients during the first wave of the pandemic. Measures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of SARS-CoV-2 PCR on combined nose and throat swabs. A multivariable predictive model including FebriDx, age, sex, and clinical characteristics was developed and underwent internal validation. RESULTS: FebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. FebriDx results were available after 10 minutes compared with 1.7 (1.6 to 2.1) hours with point-of-care PCR testing and 23.4 (17.2 to 31.1) hours with laboratory PCR testing. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model age, sex and other clinical features did not contribute significantly to the effect of the FebriDx result in distinguishing patients with and without COVID-19. CONCLUSIONS: During the first wave of the pandemic, FebriDx had high accuracy for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool. TRIAL REGISTRATION: ISRCTN14966673


title: Skull base surgery during the Covid‐19 pandemic: The Italian skull base society recommendations

text: Severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (Covid‐19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combatting the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was one of the earliest and hardest‐hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, FFP3 and/or PAPRs devices, goggles, full‐face visor, double gloves, water‐resistant gowns and protective caps, are mandatory. For negative patients, use of at least FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS‐CoV‐2, dura handling should be minimized. It is only through widely‐agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic. This article is protected by copyright. All rights reserved


title: Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin

text: Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.


title: Enhanced severity of virus associated lower respiratory tract disease in asthma patients may not be associated with delayed viral clearance and increased viral load in the upper respiratory tract

text: Abstract Background Viral respiratory infections, particularly human rhinovirus (HRV) infections, are the most common cause of asthma exacerbation. HRV infections usually lead to more severe and longer duration of lower respiratory tract (LRT) symptoms in asthmatics than in otherwise healthy individuals. However, the exact mechanism by which viruses contribute to exacerbation of asthma is unknown. Objectives The main objective of our study was to investigate the relationship of the enhanced severity of LRT symptoms to viral dynamics or cytokine responses in the upper respiratory tract (URT). Study design Therefore, we conducted a longitudinal study in which asthmatics and healthy controls were followed during natural viral respiratory tract infections. Results Our study confirmed that viral respiratory tract infections caused more severe problems of the LRT in asthma patients as compared to healthy controls. However, for all subjects, the severity of LRT symptoms were not related to viral load or prolonged viral shedding in the URT. In addition, we did not detect differences in proinflammatory cytokines in the URT between asthmatics and controls. Conclusion Persistence of the virus, as well as viral load in the URT, may not be associated with the induction and/or persistence of asthmatic symptoms.


title: Appearance of US‐like porcine epidemic diarrhoea virus (PEDV) strains before US outbreaks and genetic heterogeneity of PEDVs collected in Northern Vietnam during 2012–2015

text: Porcine epidemic diarrhoea virus (PEDV) is the aetiologic agent of porcine epidemic diarrhoea (PED), a highly contagious enteric disease that is threatening the swine industry globally. Since PED was first reported in Southern Vietnam in 2009, the disease has spread throughout the country and caused substantial economic losses. To identify PEDVs responsible for the recent outbreaks, the full‐length spike (S) gene of 25 field PEDV strains collected from seven northern provinces of Vietnam was sequenced and analysed. The sequence analysis revealed that the S genes of Vietnamese PEDVs were heterogeneous and classified into four genotypes, namely North America and Asian non‐S INDEL, Asian non‐S INDEL, new S INDEL and classical S INDEL. This study reported the pre‐existence of US‐like PEDV strains in Vietnam. Thirteen Vietnamese variants had a truncated S protein that was 261 amino acids shorter than the normal protein. We also detected one novel variant with an 8‐amino acid insertion located in the receptor‐binding region for porcine aminopeptidase N. Compared to the commercial vaccine strains, the emerging Vietnamese strains were genetically distant and had various amino acid differences in epitope regions and N‐glycosylation sites in the S protein. The development of novel vaccines based on the emerging Vietnamese strains may be contributive to the control of the current PED outbreaks.


title: Specific viral RNA drives the SARS CoV-2 nucleocapsid to phase separate

text: A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5’-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5’-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2.


title: Viral Zoonoses

text: Abstract Zoonotic viral infections represent an important public health problem across the globe. Unlike infectious agents that are limited to humans, the presence of domestic and wild animal reservoirs and insect and arthropod vectors greatly complicate transmission dynamics and make control measures very difficult to implement. Some viral zoonoses are categorized as “emerging infectious diseases” because they are newly recognized or have shown significant changes in their geographic range and/or epidemiologic characteristics. This article provides updated information on the current status of the most important viral zoonotic diseases. The recent upsurge in Ebola virus infections in West Africa and the emergence of Zika virus in the Western Hemisphere are highlighted.


title: Indications for permanent pacing in dogs and cats

text: Abstract Pacemaker implantation is considered as a standard procedure for treatment of symptomatic bradycardia in both dogs and cats. Advanced second-degree and third-degree atrioventricular blocks, sick sinus syndrome, persistent atrial standstill, and vasovagal syncope are the most common rhythm disturbances that require pacing to either alleviate clinical signs or prolong survival. Most pacemakers are implanted transvenously, using endocardial leads, but rarely epicardial leads may be necessary. To decide whether a patient is a candidate for pacing, as well as which pacing modality should be used, the clinician must have a clear understanding of the etiology, the pathophysiology, and the natural history of the most common bradyarrhythmias, as well as what result can be achieved by pacing patients with different rhythm disturbances. The goal of this review was, therefore, to describe the indications for pacing by evaluating the available evidence in both human and veterinary medicine. We described the etiology of bradyarrhythmias, clinical signs and electrocardiographic abnormalities, and the choice of pacing modality, taking into account how different choices may have different physiological consequences to selected patients. It is expected that this review will assist veterinarians in recognizing arrhythmias that may require permanent pacing and the risk-benefit of each pacing modality and its impact on outcome.


Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults


title: Stroke care during the Covid‐19 pandemic: Experience from three large European countries

text: To cope with the exponentially increasing number of patients infected by SARS‐Cov‐2, European countries carried out enormous efforts to reorganize medical assistance, and several diseases, including stroke, were particularly impacted. Herein, we report the experience of stroke neurologists from three European countries, Italy, France and Germany, that faced the pandemic at diverse time points and with different approaches, depending on their resources and health care system organization. Pre‐hospital and in‐hospital acute stroke pathways were reorganized to prioritize COVID‐19 management, and, in severely affected regions of Italy and France, stroke care was centralized to a limited number of centers while remaining stroke units were dedicated to COVID‐19 patients. The access to acute stroke diagnostics and time dependent therapies was limited or delayed because of reduced capacities of emergency services due to the burden of COVID‐19 patients. A marked reduction in the number of patients presenting with TIA and stroke was noted in the emergency departments of all three countries. Although we have only preliminary data, overall these conditions may have affected stroke outcome. These indirect effects of COVID‐19 pandemic could vanish the last years' efforts of stroke neurologists to improve outcome and reduce mortality of stroke patients. Although SARS‐Cov‐2 infection rate is slowing down in Europe, the effects of the ending lockdown in the next months are unpredictable. It is important for the European and world stroke community to share the experience learned so far to prepare for the next future and upcoming challenging times in the care of stroke patients.


title: Recently published papers: pulmonary care, pandemics, and eugenics in surviving sepsis?

text: Respiratory failure is one of the leading admission diagnoses on the critical care unit, and the journals have reflected this over the past few months. An understanding of the aetiology of pulmonary sepsis is important but your choice of ventilator gas humidification system is not. There are prophecies of more pandemics, but panic is futile because survival is all down to your genes.


title: Feline Leishmania spp. Infection in a Non-Endemic Area of Northern Italy

text: SIMPLE SUMMARY: Leishmaniosis caused by Leishmania infantum is a parasitic disease of people and animals transmitted by sand fly vectors. Although dogs in south and central Italy are most affected, in recent decades feline leishmaniosis (FeL) has become an emerging disease. This study aimed to update information on the presence of FeL in stray cats in Milan, in northern Italy; to compare these results with previous studies performed in the same area; and to report aspects of Leishmania infection in cats. A total of 117 stray cats were included and 10 (8.6%) had L. infantum infection. The parasite was identified in popliteal lymph nodes in five cats and five had antibodies against L. infantum. Most infected cats were from a specific area of Milan. Increased gammaglobulins were seen in infected cats, which also had antibodies against the pathogens Anaplasma phagocytophilum, Chlamydophila felis, and Toxoplasma gondii. There was a high prevalence of FeL in the surveyed area of northern Italy. Further studies are needed to understand if these infected cats are being imported from other areas, or if there is a real Leishmania focus in Milan. Investigation of the presence of sand fly vectors in Milan would be useful. ABSTRACT: Feline leishmaniosis (FeL) is an emerging vector-borne feline disease, with increasing numbers of cases reported and studies performed internationally. This study aimed to update the epidemiological status for FeL in stray cats in Milan, northern Italy; compare these results with previous studies in Northern Italy; and report clinicopathologic findings and coinfections in cats infected with Leishmania spp. A total of 117 cats were tested for L. infantum and retrovirus infection, hematological, and biochemical parameters. Demographic and clinical data were collected and FeL affected cats screened for selected coinfections. Overall, 10/117 (8.6%) cats tested positive for L. infantum: in five cats L. infantum DNA was found in popliteal lymph nodes and five were IFAT seropositive at titers from 1:80 to 1:160. Infected cats were concentrated in a specific area of Milan (p = 0.0154). No specific clinicopathologic abnormalities or retroviral infections were significantly linked to the infection, other than hypergammaglobulinemia (p = 0.0127). Seroreactivity to Anaplasma phagocytophilum, Chlamydophila felis, and Toxoplasma gondii was found in some infected cats. A high prevalence of FeL was found in a non-endemic area of northern Italy and future studies should continually monitor this data to understand whether these cases are imported or if Leishmania vectors are present in this area.


title: Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences

text: Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria-infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.


title: Respiratory Infections, Acute

text: Abstract Acute respiratory tract infections are an extremely common and important source of morbidity and mortality. Despite advances in our understanding of microbial pathogens and the development of novel antimicrobial agents, acute respiratory tract infections continue to place an enormous burden on global health expenditure. Acute respiratory tract infections can be divided into infections that predominantly affect the upper respiratory tract above the vocal cords and those that affect the lower respiratory tract. The clinical features, causative pathogens, and therapies of common acute respiratory tract infections are detailed in this article.


title: Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2

text: The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding “up” conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.


title: Monitoring en surveillance: is de huidige situatie adequaat?

text: De huidige surveillance in Nederland kent diverse systemen, die elkaar deels aanvullen en elkaar voor een klein deel overlappen, te weten het systeem van aangifteplichtige infectieziekten, surveillance via de CMR-peilstations (45 huisartsenpraktijken verspreid over het land), de doodsoorzakenregistratie van het CBS en op aanwijzing rapportage van bepaalde ziekten door ziekenhuizen en instellingen. Syndroomsurveillance combineert de gegevens van meerdere systemen tegelijk. Het CMR-peilstationssysteem bleek een belangrijke gegevensbron bij de pandemie in 2009. Verbetering van surveillance in de huisartsenpraktijk is mogelijk door meer deelnemende praktijken en een hoge prioritering bij alle HIS-leveranciers voor het optimaliseren van de HIS’sen ten bate van surveillance. De surveillance moet zo weinig mogelijk inspanning vergen van clinici, voor wie de behandeling van de patiënt centraal moeten blijven staan, maar moet wel valide gegevens opleveren. Accurate ICPC-codering is daarbij onontbeerlijk.


title: Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review

text: Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.


title: Saliva is a non‐negligible factor in the spread of COVID‐19

text: SARS‐CoV‐2, a novel emerging coronavirus, has caused severe disease (COVID‐19), and rapidly spread worldwide since the beginning of 2020. SARS‐CoV‐2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS‐CoV‐2 has been detected in saliva samples, making saliva a potential transmission route for COVID‐19. The participants in dental practice confront a particular risk of SARS‐CoV‐2 infection due to close contact with the patients and potential exposure to saliva‐contaminated droplets and aerosols generated during dental procedures. In addition, saliva‐contaminated surfaces could lead to potential cross‐infection. Hence, the control of saliva‐related transmission in the dental clinic is critical, particularly in the epidemic period of COVID‐19. Based on our experience of the COVID‐19 epidemic, some protective measures that can help reduce the risk of saliva‐related transmission are suggested, in order to avoid the potential spread of SARS‐CoV‐2 among patients, visitors, and dental practitioners.


title: Threat to democracy: Physical and mental health impact of democracy movement in Hong Kong

text: Abstract Background This study examined the prevalence and critical predictors of anxiety and depressive symptoms and self-rated health, following the Umbrella Movement in Hong Kong. Methods: Random digit dialing recruited a population-representative sample of 1208 Chinese Hong Kong citizens (mean age=46.89 years; 63% female) in the first two weeks of February 2015. Respondents gave their informed consent and reported personal, social, and economic resource loss since the Umbrella Movement (Conservation of Resources-Evaluation), current anxiety symptoms (State-Trait Anxiety Inventory) and depressive symptoms (Patient Health Questionnaire-9), and self-rated health (1=very good, 4=very bad). Results A total of 47.35% (95% CI=44.55, 50.17) respondents reported moderate/severe anxiety symptoms and 14.4% (95% CI=12.54, 16.50) reported moderate/severe depressive symptoms; 9.11% (95% CI=7.61, 10.86) reported “poor” or “very poor” health. Multivariable regressions revealed that personal and social resource loss was associated with higher anxiety and depressive symptoms and greater odds of “very poor” health (adjusted odds ratios/incidence rate ratios=5–102%), independent of lower education level and income and being unmarried. Limitations This study was cross-sectional in nature and thus could not determine causality from the associations between resource loss and outcome variables. Second, the telephone survey relied on self-reports; response bias and social desirability could influence respondents' answers and discount data validity. Third, potential confounders such as preexisting mental and physical health issues and concurrent predictors like exposure to the Umbrella Movement were not assessed. Conclusions This is one of the first studies following any recent political movement (e.g., The Arab Spring) to quantify distress and the associated correlates of distress among affected citizens. Perceived psychosocial resource losses were critical predictors of poor outcomes.


title: Head and neck survivorship care in the times of the SARS‐CoV‐2 pandemic

text: With the arrival of the coronavirus disease (SARS‐CoV‐2) in the United States, care practice paradigms have drastically changed. Data from China suggest that the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS‐CoV‐2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for patients with cancer, and increasing monitoring if a patient becomes infected with SARS‐CoV‐2. In this present commentary, we discuss the unique mental health challenges and burdens of patients with head and neck cancer in the times of the SARS‐CoV‐2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system.


title: Modeling the epidemic dynamics and control of COVID-19 outbreak in China

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) is rapidly spreading in China and more than 30 countries over last two months. COVID-19 has multiple characteristics distinct from other infectious diseases, including high infectivity during incubation, time delay between real dynamics and daily observed number of confirmed cases, and the intervention effects of implemented quarantine and control measures. METHODS: We develop a Susceptible, Un-quanrantined infected, Quarantined infected, Confirmed infected (SUQC) model to characterize the dynamics of COVID-19 and explicitly parameterize the intervention effects of control measures, which is more suitable for analysis than other existing epidemic models. RESULTS: The SUQC model is applied to the daily released data of the confirmed infections to analyze the outbreak of COVID-19 in Wuhan, Hubei (excluding Wuhan), China (excluding Hubei) and four first-tier cities of China. We found that, before January 30, 2020, all these regions except Beijing had a reproductive number R > 1, and after January 30, all regions had a reproductive number R < 1, indicating that the quarantine and control measures are effective in preventing the spread of COVID-19. The confirmation rate of Wuhan estimated by our model is 0.0643, substantially lower than that of Hubei excluding Wuhan (0.1914), and that of China excluding Hubei (0.2189), but it jumps to 0.3229 after February 12 when clinical evidence was adopted in new diagnosis guidelines. The number of unquarantined infected cases in Wuhan on February 12, 2020 is estimated to be 3,509 and declines to 334 on February 21, 2020. After fitting the model with data as of February 21, 2020, we predict that the end time of COVID-19 in Wuhan and Hubei is around late March, around mid March for China excluding Hubei, and before early March 2020 for the four tier-one cities. A total of 80,511 individuals are estimated to be infected in China, among which 49,510 are from Wuhan, 17,679 from Hubei (excluding Wuhan), and the rest 13,322 from other regions of China (excluding Hubei). Note that the estimates are from a deterministic ODE model and should be interpreted with some uncertainty. CONCLUSIONS: We suggest that rigorous quarantine and control measures should be kept before early March in Beijing, Shanghai, Guangzhou and Shenzhen, and before late March in Hubei. The model can also be useful to predict the trend of epidemic and provide quantitative guide for other countries at high risk of outbreak, such as South Korea, Japan, Italy and Iran. [Image: see text] SUPPLEMENTARY MATERIALS: The supplementary materials can be found online with this article at 10.1007/s40484-020-0199-0.


COVID19: Emerging lessons from the pandemic


title: Development of monoclonal antibodies (MAbs) to feline interferon (fIFN)-γ as tools to evaluate cellular immune responses to feline infectious peritonitis virus (FIPV)

text: Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). The antibody-dependent enhancement (ADE) of FIPV infection has been recognised in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of FIP. To evaluate the importance of cellular immunity for FIPV infection, monoclonal antibodies (MAbs) against feline interferon (fIFN)-γ were first created to establish fIFN-γ detection systems using the MAbs. Six anti-fIFN-γ MAbs were created. Then, the difference in epitope which those MAbs recognise was demonstrated by competitive enzyme-linked immunosorbent assay (ELISA) and IFN-γ neutralisation tests. Detection systems for fIFN-γ (sandwich ELISA, ELISpot assay, and two-colour flow cytometry) were established using anti-fIFN-γ MAbs that recognise different epitopes. In all tests, fIFN-γ production from peripheral blood mononuclear cells (PBMCs) obtained from cats experimentally infected with an FIPV isolate that did not develop the disease was significantly increased by heat-inactivated FIPV stimulation in comparison with medium alone. Especially, CD8+fIFN-γ + cells, but not CD4+fIFN-γ + cells, were increased. In contrast, fIFN-γ production from PBMCs isolated from cats that had developed FIP and specific pathogen-free (SPF) cats was not increased by heat-inactivated FIPV stimulation. These results suggest that cellular immunity plays an important role in preventing the development of FIP. Measurement of fIFN-γ production with the anti-fIFN-γ MAbs created in this study appeared to be useful in evaluating cellular immunity in cats.


title: Modelos experimentales de desmielinización-remielinización

text: INTRODUCTION: Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. DEVELOPMENT: We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. CONCLUSIONS: Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study.


title: Complete Genome Analysis of Canine Respiratory Coronavirus

text: The canine respiratory coronavirus (CRCoV) K37 strain of the family Coronaviridae, group 2, was isolated in South Korea. Its genome was analyzed by nucleotide sequencing and was determined to have 31,029 bp. The small open reading frames situated between the spike and envelope genes of most of the CRCoV strains (except the CRCoV 4180 strain) were found to encode three nonstructural proteins (4.9 kDa, 2.7 kDa, and 12.8 kDa), while those of bovine coronavirus (BCoV) encode another three nonstructural proteins (4.9 kDa, 4.8 kDa, and 12.7 kDa) and those of a recently isolated bovine respiratory coronavirus (BRCoV) were found to encode only two nonstructural proteins (4.9 kDa and 12.7 kDa). The differences in the genes encoding these small nonstructural proteins may be associated with the emergence of highly similar viruses in different hosts.


title: A Comparative Study of Clinical Features and Outcomes in Young and Older Adults with Severe Acute Respiratory Syndrome

text: Objectives: To determine the clinical presentation, findings, and outcomes of older adults (> 60) with severe acute respiratory syndrome (SARS) and compare these with a control group of younger patients (≤60). Design: Retrospective cohort study. Setting: A community‐based, acute hospital in Hong Kong. Participants: All adult inpatients with a clinical diagnosis of SARS. Measurements: Clinical presentations, investigations, treatment, and 30‐ and 150‐day mortality. Results: There were 52 young and 25 older patients with a mean age±standard deviation of 39.5±11.7 and 72.1±7.2, respectively. Fever, chills, and diarrhea were more common in younger patients, whereas decrease in appetite and general condition occurred only in older patients. The prevalence of positive reverse‐transcriptase polymerase chain reaction for SARS‐associated coronavirus (SARS‐CoV) in nasopharyngeal secretions and stool samples was similar in the two groups. The prevalence of positive serological tests for SARS‐CoV was significantly lower in older patients (42% vs 92%, P<.001). This was largely due to incomplete testing in elderly patients. Older patients were more likely to develop secondary nosocomial infection, be admitted to an intensive care unit, and require mechanical ventilation. The cumulative 30‐ and 150‐day mortality rates were 3.8% and 7.6%, respectively, in young patients with SARS and 56% and 60%, respectively, in older patients (P<.001). Conclusion: Older patients with SARS more often presented with nonspecific symptoms, and the prognosis was poor. Reverse‐transcriptase polymerase chain reaction was useful in diagnosing SARS in older patients, but the role of serological tests in individual elderly is limited.


title: Does SARS‐CoV‐2 has a longer incubation period than SARS and MERS?

text: The outbreak of a novel coronavirus (SARS‐CoV‐2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS‐CoV‐2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS‐CoV‐2, severe acute respiratory syndrome coronavirus (SARS‐CoV), and middle east respiratory syndrome coronavirus (MERS‐CoV), highlighting the need for larger and well‐annotated datasets.


title: Nasopharyngeal and Oropharyngeal Swabs, And/Or Serology for SARS COVID-19: What Are We Looking For?

text: Governments and clinicians that were fully involved in the dramatic SARS-CoV-2 outbreak during the last few weeks in Italy (and more or less all over the world) are fiercely debating the use of methods for screening this viral infection. Thus, all countries are employing a lot of resources in order to test more and more subjects. For this purpose, there are different strategies, based on either direct or indirect tests. Among the first category, the main assays used for SARS-CoV-2 are based on a real-time reverse transcriptase polymerase chain reaction (RT-PCR). Such tests can be performed on nasopharyngeal and oropharyngeal swabs for the categories of those with symptoms and those potentially exposed. In order to integrate the molecular assays in the diagnosis of SARS-CoV-2, a wide range of serology immunoassays (IAs) have also been developed. If we want to identify “immune” people in order to let them to come back to work, serology is the best (and probably the only) approach.


title: Hemagglutinin-targeting Artificial MicroRNAs Expressed by Adenovirus Protect Mice From Different Clades of H5N1 Infection

text: Influenza virus (IV) is a continuously evolving virus that widely spreads in humans and contributes to substantial morbidity and mortality. Re-emergence of human infection with avian influenza virus H5N1 poses extra challenge to IV control. Artificial microRNA (amiRNA)-mediated RNA interference has become a powerful antiviral approach due to its high specificity and rapid effect. Here, we designed several amiRNAs targeting the hemagglutinin gene of H5N1, a major determinant of pathogenicity. Expression and delivery efficiency were enhanced by presenting functional amiRNA with chimpanzee adenovirus serotype 68 (AdC68). One amiRNA, HA-1405, significantly limited H5N1 replication in vitro and inhibited 96.7% of clade 2.3.2 replication. AdC68-conjugated HA-1405 treatment remarkably decreased different clades of H5N1 plaque formation in Madin–Darby canine kidney cells. Moreover, prophylactic administration with rAd(HA-1405) markedly alleviated clinical symptoms and reduced ~3- to 40-folds of lung viral RNA copies against four clades of H5N1 in Institute of Cancer Research (ICR) mice. Our results further showed that rAd(HA-1405) conferred 70 and 40% immediate protection against lethal clade 2.3.2 and clade 2.3.4 H5N1 challenge, respectively. In conclusion, these data provided information that HA-targeting amiRNA delivered by AdC68 could be pursued as a potential agent for highly pathogenic avian influenza viruses prevention.


COVID-19, QUARANTINE, AND ATOPIC DERMATITIS


title: Planning and managing a COVID‐19 mobile testing site

text: The State University of New York at Albany is contributing to the battle against COVID‐19 in numerous ways, from donations of personal protective equipment to the 3D printing of protective face shields.


title: Glycyrrhizin Inhibits Interleukin-8 Production and Nuclear Factor–κ B Activity in Lung Epithelial Cells, but Not Through Glucocorticoid Receptors

text: Abstract This study was designed to examine the glucocorticoid-like inhibitory effect of glycyrrhizin (GL) on interleukin (IL)-8 production in A549 lung epithelial cells. GL, as well as dexamethasone (DEX) inhibited both tumor necrosis factor (TNF)-α –and IL-1β –induced IL-8 production, mRNA expression, and promoter activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear factor (NF)-κ B, without inhibiting translocation of the NF-κ B p65 subunit to the nucleus. However, the effect of GL was insensitive to RU486, a GR antagonist, and to GR knockdown by siRNA. Furthermore, only GL inhibited DNA binding of p65 to the IL-8 promoter region. These findings indicated that GL had a glucocorticoid-like inhibitory effect on IL-8 production via a mechanism that differs from that of glucocorticoids.


title: Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

text: In vitro, nitric oxide (NO) has been shown to have antimicrobial activity against a wide range of viruses, including influenza A virus. Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. NO was delivered to influenza-infected mice either continuously or intermittently at 80 or 160 ppm, respectively, using both prophylactic and post-infection treatment strategies. Murine survival and weight loss were assessed, and lung viral load was quantified via plaque assay. Here, we report that iNO administered prophylactically or post-influenza infection failed to improve survival of infected mice. No difference in lung viral load was observed between experimental groups. Although NO has antiviral activity against influenza A virus in vitro, iNO therapy provided no apparent benefit when used for treatment of influenza A virus infection in vivo.


title: Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: Network-molecular docking-LC–MS(E) analysis

text: OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein–protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent–target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target–constituent–disease network. Twelve disease pathways attributed to the Lung–Large Intestine meridians, with six and five attributed to the Kidney–Urinary Bladder and Stomach–Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL(pro)), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL(pro) inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION: RDS acts primarily in the Lung–Large Intestine, Kidney–Urinary Bladder and Stomach–Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS’s dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.


title: Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

text: The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.


title: The covid‐19 pandemic, personal protective equipment, and respirator: a narrative review

text: The coronavirus disease 2019 (COVID‐19) pandemic has touched almost every continent. Personal protective equipment (PPE) is the final line of protection of healthcare workers (HCW). There is variation as well as controversy of infection control recommendation with regards to the use of PPE for HCW between institutions. The aim of this narrative review is to of examine and summarise the available evidence to guide recommendation for the safety of HCW. A literature search was conducted on the PubMed, MedLine, and Embase databases with the keywords “personal protective equipment”, “COVID 19”, “n95”, “health care worker”, and “mortality”. SARS‐nCoV‐2 is highly contagious. 3.5‐20% of HCW has been reported to be infected. The mortality ranges from 0.53‐1.94%. PPE is part of the measure within a package of prevention and control of pandemic, rather than a replacement of. Respirators are more effective than masks in preventing aerosol transmission to HCWs. Extended use may be considered if guidelines are adhered. PAPRs if available should be used in high risk procedures. Transmission of viruses is multimodal, and in the setting of a novel pathogen with high case fatality with no proven effective interventions, PPE that affords the best protection should be available to HCWs.


title: A Proposed Process for Risk Mitigation During the COVID-19 Pandemic

text: Recent executive orders have led some applied behavior analysis (ABA) providers to interpret themselves as “essential personnel” during the COVID-19 pandemic. In this article, we argue against a blanket interpretation that being labeled “essential personnel” means that all in-person ABA services for all clients should continue during the COVID-19 pandemic. We believe this argument holds even if ABA providers are not in a jurisdiction currently under an active shelter-at-home or related order. First, we provide a brief description of risks associated with continued in-person ABA service delivery, as well as risks associated with the temporary suspension of services or the transition to remote ABA service delivery. For many clients, continued in-person service delivery carries a significant risk of severe harm to the client, family and caregivers, staff, and a currently overburdened health care system. In these situations, ABA providers should temporarily suspend services or transition to telehealth or other forms of remote service delivery until information from federal, state, and local health care experts deems in-person contact safe. In rare cases, temporary suspension of services or a transition to remote service delivery may place the client or others at risk of significant harm. In these situations, in-person services should likely continue, and ongoing assessment and risk mitigation are essential.


title: Screening of commercial meat products from supermarket chains for feline derivatives using SP-PCR-RLFP and lab-on-a-chip

text: Determination of feline meat in food products is an important issue for social, health, economic and religious concern. Hence this paper documented the application of species specific polymerase chain reaction-restriction fragment length polymorphism (SP-PCR-RFLP) assay targeting a short-fragments (69 bp) of mitochondrial cytochrome b (cytb) gene to screen feline meat in commercial meat products using lab-on-a-chip. The SP-PCR assay proved its specificity theoretically and experimentally while testing with different common animal, aquatic and plant species of DNA. The feline specific (69 bp, 43- and 26-bp) characteristic molecular DNA pattern was observed by SP-PCR and RFLP analysis. For assay performance, it was tested in three different types of commercial dummy meat products such as frankfurters, nuggets and meatballs and digested with AluI-restriction enzyme. The highest sensitivity of the assay using lab-on-a-chip was as low as 0.1 pg or 0.01% (w/w) in commercial dummy meat products. We have also applied this assay to screen three important commercial meat products of six different brand from six supermarket chains located at three different states of Malaysia. Thus total 378 samples were tested to validate the specificity, sensitivity, stability of the assay and utilization of it for commercial meat product screening.


COVID-19 and Stigma: Social discrimination towards frontline healthcare providers and COVID-19 recovered patients in Nepal


COVID-19 should be recognized as an occupational disease worldwide


title: SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns

text: “Severe acute respiratory syndrome” (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.


title: Molecular simulation study of the binding mechanism of [α-PTi(2)W(10)O(40)](7−) for its promising broad-spectrum inhibitory activity to FluV-A neuraminidase

text: Polyoxometalate (POM) has promising antiviral activities. It shows broad-spectrum inhibiting ability, high efficiency, and low toxicity. Experimental assays show that titanium containing polyoxotungstates have anti-influenza-virus activity. In this paper, the binding mechanisms of five isomers of di-Ti-substituted polyoxotungstate, [α-1,2-PTi(2)W(10)O(40)](7−) (α-1,2), [α-1,6-PTi(2)W(10)O(40)](7−) (α-1,6), [α-1,5-PTi(2)W(10)O(40)](7−) (α-1,5), [α-1,4-PTi(2)W(10)O(40)](7−) (α-1,4) and [α-1,11-PTi(2)W(10)O(40)](7−) (α-1,11), to five subtypes of influenza virus A neuraminidase (FluV-A NA) were investigated in the context of aqueous solution by using molecular docking and molecular dynamics studies. The results show that the isomer α-1,2 is superior to other isomers as a potential inhibitor to neuraminidase. The positively charged arginine residues around the active site of NA could be induced by negatively charged POM to adapt themselves and could form salt bridge interactions and hydrogen bond interactions with POM. The binding free energies of POM/NA complexes range from −5.36 to −8.31 kcal mol(−1). The electrostatic interactions are found to be the driving force during the binding process of POM to NA. The conformational analysis shows that POM tends to bind primarily with N1 and N8 at the edge of the active pocket, which causes the conformational change of the pincers structure comprising residue 347 and loop 150. Whereas, the active pockets of N2, N9 and N4 are found to be more spacious, which allows POM to enter into the active pockets directly and anchor there firmly. This study shows that negatively charged ligand as POM could induce the reorganization of the active site of NA and highlights POM as a promising inhibitor to NA despite the ever increasing mutants of NA. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11434-010-3271-8 and is accessible for authorized users.


title: Mycoplasma alkalescens demonstrated in bronchoalveolar lavage of cattle in Denmark

text: Mycoplasma alkalescens is an arginine-metabolizing mycoplasma, which has been found in association with mastitis and arthritis in cattle. Routine bacteriological examination of 17 bronchoalveolar lavage samples from calves with pneumonia in a single herd in Denmark, identified M. alkalescens in eight samples. The organism was found as a sole bacterilogical findings in five of the samples as well as in combination with Mannheimia haemolytica, Haemophilus somni and Salmonella Dublin. This is the first report of isolation of M. alkalescens in Denmark.