title: Respiratory syncytial virus prolifically infects N2a neuronal cells, leading to TLR4 and nucleolin protein modulations and RSV F protein co-localization with TLR4 and nucleolin

text: BACKGROUND: Respiratory syncytial virus (RSV) infects the central nervous system, resulting in neurological symptoms. However, the precise underlying pathogenic mechanisms have not been elucidated. In the present study, the infectivity of RSV on N2a neuronal cells and the possible roles of Toll-like receptor 4 (TLR4) and nucleolin (C23) during RSV infection were investigated. METHODS: We compared two experimental groups (infected and non-infected) and monitored the RSV viral titers in the culture supernatant by a viral plaque assay. We also inspected the morphology of the nucleus in infected N2a cells. We measured the level of RSV F protein and studied its co-localization with TLR4 and nucleolin using immunofluorescence assays and laser confocal microscopy. The potential interaction of RSV F protein with TLR4 and nucleolin was examined by coimmunoprecipitation. The expression changes of TLR4, nucleolin, TLR3 and TLR7 proteins in N2a cells and IL-6 and TNF-α in the culture supernatant were investigated by Western Blot analysis and ELISA assay. Changes in neuronal cell apoptosis status was examined by flow cytometry. RESULTS: The results demonstrated prolific RSV infection of N2a cells, which triggered a decrease of NeuN protein expression, coinciding with an increase of nuclear lesions, F protein expression, RSV viral titers, and late apoptotic levels of N2a cells. RSV infection induced co-localization of RSV F protein with TLR4 and nucleolin, which could potentially lead to a direct interaction. Furthermore, it was found that TLR4 and nucleolin levels increased early after infection and decreased subsequently, whereas TLR3 and TLR7 expression increased throughout RSV infection. CONCLUSION: The RSV Long strain can prolifically infect N2a neuronal cells, modulating the expression of TLR4 and nucleolin, as well as TLR3, TLR7 and their downstream inflammatory factors, and inducing the co-localization of the RSV F protein with TLR4 and nucleolin.


title: Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs

text: Influenza is a contagious respiratory acute viral disease characterized by a short incubation period, high fever and respiratory and systemic symptoms. The burden of influenza is very heavy. Indeed, the World Health Organization (WHO) estimates that annual epidemics affect 5-15% of the world's population, causing up to 4-5 million severe cases and from 250,000 to 500,000 deaths. In order to design anti-influenza molecules and compounds, it is important to understand the complex replication cycle of the influenza virus. Replication is achieved through various stages. First, the virus must engage the sialic acid receptors present on the free surface of the cells of the respiratory tract. The virus can then enter the cells by different routes (clathrin-mediated endocytosis or CME, caveolae-dependent endocytosis or CDE, clathrin-caveolae-independent endocytosis, or macropinocytosis). CME is the most usual pathway; the virus is internalized into an endosomal compartment, from which it must emerge in order to release its nucleic acid into the cytosol. The ribonucleoprotein must then reach the nucleus in order to begin the process of translation of its genes and to transcribe and replicate its nucleic acid. Subsequently, the RNA segments, surrounded by the nucleoproteins, must migrate to the cell membrane in order to enable viral assembly. Finally, the virus must be freed to invade other cells of the respiratory tract. All this is achieved through a synchronized action of molecules that perform multiple enzymatic and catalytic reactions, currently known only in part, and for which many inhibitory or competitive molecules have been studied. Some of these studies have led to the development of drugs that have been approved, such as Amantadine, Rimantadine, Oseltamivir, Zanamivir, Peramivir, Laninamivir, Ribavirin and Arbidol. This review focuses on the influenza lifecycle and on the currently available drugs, while potential antiviral compounds for the prevention and treatment of influenza are considered in the subsequent review.


Third Strain of Porcine Epidemic Diarrhea Virus, United States


title: Sensing Microbial RNA in the Cytosol

text: The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response.


Good science is good science: we need specialists, not sects


title: Coronavirus pandemic: A time for reflection

text: At the time of writing, it is six weeks since Prime Minister Boris Johnson made his live televised speech calling on the country to unite, stay at home and save lives In that time all of our lives had been impacted by the COVID-19 pandemic Mick Armstrong's open letter to members in last month's issue drew attention to the size and pace of that impact, and that the BDA is committed to doing the very best for each and every one of you


title: A Novel Strategy for Analyzing RNA-Protein Interactions by Surface Plasmon Resonance Biosensor

text: Surface plasmon resonance (SPR) biosensor is a promising technology for its various advantages including the real-time measurement of biomolecular interactions without labeling. A method of hybridizing RNAs on the surface of the streptavidin-coated (SA) sensor chip to study RNA-protein interactions was described in this paper. In our study, it has been shown that the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has a high binding affinity for the leader sequence of SARS-CoV genome. Effect of temperature on the RNA-DNA hybridization was also examined. This method can provide the affinity of interactions with high sensitivity. Therefore, it will be useful in screening binding candidates for a given RNA target motif with one chip.


title: Quality of Respiratory Infection Disease Prevention in Outpatient and Emergency Departments in Hospitals in Inner Mongolia, China: An Exit Poll Survey

text: PURPOSE: Measures to prevent respiratory infection diseases (RIDs) in hospitals are important to protect both patients and physicians. In 2003, an outbreak of severe acute respiratory syndrome occurred in Inner Mongolia Autonomous Region (IMAR) of China. We aimed to evaluate competency in RID prevention procedures in terms of hospital performance and physician behavior. PATIENTS AND METHODS: We conducted a cross-sectional study in 10 tertiary general public hospitals in 3 cities of IMAR. In each hospital, we chose the respiratory and ear–nose–throat outpatient departments (OPDs) and the emergency department (ED) to invite patients with symptoms of cough to join the study before they consulted a physician. After their consultation, we asked the patients to complete a checklist to score the performance of the departments and the behavior of their physicians in terms of RID prevention practices according to international professional guidelines. RESULTS: From 711 respondents, in the domain of hospital performance, display of posters on directive to wash hands after coughing/sneezing had an average score of 0.452 (range 0–1), while other cough etiquette items had scores averaging between 0.33 and 0.39. The average score for air ventilation was 0.66. For physicians’ performance, informing patients the location of handwashing facilities scored the highest (0.62), while low scores were seen for offering a mask to coughing patients (0.14) and encouraging coughing patients to distance themselves from others (0.17). Most RID prevention procedures received low scores in EDs in both hospital performance and physician behavior domains. CONCLUSION: Hospitals in IMAR should improve their performance in RID prevention procedures, especially in giving information to RID patients through the display of posters. The practice of physicians in preventing respiratory infection spread was suboptimum. ED staff and hospital administrators should improve their procedures to prevent the spread of respiratory infections, especially given the increasing occurrences of global pandemics such as COVID-19.


title: Epidemiology reveals mask wearing by the public is crucial for COVID-19 control

text: Abstract Objective The pandemic 2019 Coronavirus disease (COVID-19) is the greatest concern globally. Here we analyzed the epidemiological features of China, South Korea, Italy and Spain to find out the relationship of major public health events and epidemiological curves. Study design In this study we describe and analyze the epidemiological characteristics of COVID-19 in and outside China. We use GAM to generate the epidemiological curves and simulate infection curves with reported incubation period. Results The epidemiological curved derived from the GAM suggested that the infection curve can reflect the public health measurements sensitively. Under the massive actions token in China, the infection curve flattened at 23rd of January. While surprisingly, even before Wuhan lockdown and first level response of public emergency in Guangdong and Shanghai, those infection curve came to the reflection point both at 21st of January, which indicated the mask wearing by the public before 21st Jan were the key measure to cut off the transmission. In the countries outside China, infection curve also changed in response to measures, but its rate of decline was much smaller than the curve of China's. Conclusion The present analysis comparing the epidemiological curves in China, South Korea, Italy and Spain supports the importance of mask wearing by the public. Analysis of the infection curve helped to clarify the impact of important public health events, evaluate the efficiencies of prevention measures, and showed wearing masks in public resulted in significantly reduced daily infected cases.


title: Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial

text: Abstract Quercetin in culture with target cells and pathogens exerts anti-pathogenic activities against a wide variety of viruses and bacteria. A few small-scale human quercetin supplementation studies have produced conflicting results regarding quercetin's effects on upper respiratory tract infection rates, and little is known regarding the appropriate human dose. The purpose of this randomized, double-blinded, placebo-controlled trial was to measure the influence of two quercetin doses (500 and 1000mg/day) compared to placebo on upper respiratory tract infection (URTI) rates in a large community group (N =1002) of subjects varying widely in age (18–85 years). Subjects ingested supplements for 12 weeks and logged URTI symptoms on a daily basis using the Wisconsin Upper Respiratory Symptom Survey (WURSS). No significant group differences were measured for URTI outcomes for all subjects combined, or when analyzing separately by gender, body mass index, and age categories. Regression analysis revealed that the strongest interaction effect with group status was self-reported fitness level. A separate analysis of subjects 40 years of age and older rating themselves in the top half of the entire group for fitness level (N =325) showed lower URTI severity (36% reduction, P =0.020) and URTI total sick days (31% reduction, P =0.048) for the Q-1000 group compared to placebo. In summary, for all subjects combined, quercetin supplementation over 12 weeks had no significant influence on URTI rates or symptomatology compared to placebo. A reduction in URTI total sick days and severity was noted in middle aged and older subjects ingesting 1000mgquercetin/day for 12 weeks who rated themselves as physically fit.


title: Newly identified human rhinoviruses: molecular methods heat up the cold viruses

text: Human rhinovirus (HRV) infections cause at least 70% of virus‐related wheezing exacerbations and cold and flu‐like illnesses. They are associated with otitis media, sinusitis and pneumonia. Annually, the economic impact of HRV infections costs billions in healthcare and lost productivity. Since 1987, 100 officially recognised HRV serotypes reside in two genetically distinct species; HRV A and HRV B, within the genus Enterovirus, family Picornaviridae. Sequencing of their ∼7kb genomes was finalised in 2009. Since 1999, many globally circulating, molecularly‐defined ‘strains’, perhaps equivalent to novel serotypes, have been discovered but remain uncharacterised. Many of these currently unculturable strains have been assigned to a proposed new species, HRV C although confusion exists over the membership of the species. There has not been sufficient sampling to ensure the identification of all strains and no consensus criteria exist to define whether clinical HRV detections are best described as a distinct strain or a closely related variant of a previously identified strain (or serotype). We cannot yet robustly identify patterns in the circulation of newly identified HRVs (niHRVs) or the full range of associated illnesses and more data are required. Many questions arise from this new found diversity: what drives the development of so many distinct viruses compared to other species of RNA viruses? What role does recombination play in generating this diversity? Are there species‐ or strain‐specific circulation patterns and clinical outcomes? Are divergent strains sensitive to existing capsid‐binding antivirals? This update reviews the findings that trigger these and other questions arising during the current cycle of intense rhinovirus discovery. Copyright © 2010 John Wiley & Sons, Ltd.


Comment on “Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade”


title: A re-examination of tourism and peace: The case of the Mt. Gumgang tourism development on the Korean Peninsula

text: Tourism can transcend governmental boundaries by bringing people closer together through the understanding of different cultures, heritages, and beliefs. Therefore, it is potentially one of the most important vehicles for promoting peace among the peoples of the world. Although previous South Korean governments have historically proposed a variety of actions to contribute to peace on the Korean Peninsula, there has been little success. However, the Mt. Gumgang tourism development, the hallmark of the Sunshine Policy of former president of South Korea, Dae Jung Kim, is different from previous tourism initiatives as it has had more tangible and practical outcomes that have contributed to the promotion of peace on the divided Peninsula. To this end, the South Korean government has applied the insights of neofunctionalism to the Mt. Gumgang tourism development. This is an approach to integration theory from the perspective of liberalism that has been heralded in international politics. According to this approach, it is expected that the Mt. Gumgang tourism development can be used as a tool to maintain peaceful circumstances, which results in spill-over effects, enlargement of activity scopes, and a heightened level of commitment on the Korean Peninsula. The purpose of this study is to empirically test the hypothesis that the Mt. Gumgang tourism development contributes to the peace of the Korean Peninsula by employing the theory of neofunctionalism. To test this hypothesis, this study proposes a Peace Index and investigates the spill-over effects by utilizing the Mt. Gumgang tourism development as a test case. The results of this study indicate that the view that tourism contributes to peace is valid but tenuous since the impact of the Mt. Gumgang tourism development in the promotion of peace was less significant than expected. Consequently, the results of this study also indicate that neofunctionalism, which has been developed for western political systems, needs to be re-examined when applied to the unique, dynamic, and complex political circumstances on the Korean Peninsula.


title: State-of-art review of information diffusion models and their impact on social network vulnerabilities

text: Abstract With the development of information society and network technology, people increasingly depend on information found on the Internet. At the same time, the models of information diffusion on the Internet are changing as well. However, these models experience the problem due to the fast development of network technologies. There is no thorough research in regards to the latest models and their applications and advantages. As a result, it is essential to have a comprehensive study of information diffusion models. The primary goal of this research is to provide a comparative study on the existing models such as the Ising model, Sznajd model, SIR model, SICR model, Game theory and social networking services models. We discuss several of their applications with the existing limitations and further categorizations. Vulnerabilities and privacy challenges of information diffusion models are extensively explored. Furthermore, categorization including strengths and weaknesses are discussed. Finally, limitations and recommendations are suggested with diverse solutions for the improvement of the information diffusion models and envisioned future research directions.


title: A Graphene‐Based Platform for the Assay of Duplex‐DNA Unwinding by Helicase

text: Mit bloßen Auge zu erkennen: Mithilfe von Graphenoxid (GO) kann die Helicase‐abhängige Entwindung doppelsträngiger DNA (dsDNA) quantitativ und in Echtzeit verfolgt werden. GO bindet selektiv an entwundene fluoreszenzmarkierte einzelsträngige DNA und löscht die Fluoreszenz (siehe Bild). Die Helicaseaktivität wird über die Fluoreszenzänderung registriert.[Image: see text]


title: Massive coronary thrombosis caused primary percutaneous coronary intervention to fail in a COVID‐19 patient with ST‐elevation myocardial infarction

text: COVID‐19 is a new viral infection that has a significant impact on global health and economy. Because of its rapid spread worldwide, it may influence the prognosis of other medical conditions, such as ST‐segment elevation myocardial infarction (STEMI). We report a case of a 58‐year female patient admitted with an infero‐posterior STEMI on the background of recently positive COVID‐19 swab. Reperfusion was attempted through primary PCI but unfortunately failed to restore coronary blood flow due to massive thrombotic burden despite several attempts of balloon dilatation and aspiration thrombectomy. She sadly died later on because of hemodynamic deterioration. This scenario raises concerns about Neutrophil Extracellular Traps (NETS) which might potentially have propagated inflammation and thrombosis via platelets' aggregation leading to enhanced coagulopathy and massive coronary thrombosis. Therefore, we suggest primary PCI as the first‐choice of revascularization in patients with combined COVID‐19 and STEMI. Additionally, we emphasize on the importance of using the potent new generation P2Y12 inhibitors along with GPIIb/IIIa inhibitors in every STEMI patient with COVID‐19 to achieve favorable conditions for primary PCI as well as favorable outcomes after stent implantation.


title: Burden of Healthcare-Associated Viral Respiratory Infections in Children’s Hospitals

text: OBJECTIVE: Although healthcare-associated (HA) viral respiratory infections (VRIs) are common in pediatrics, no benchmark for comparison exists. We aimed to determine, compare, and assess determinants of unit-specific HA-VRI incidence rates in 2 children’s hospitals. METHODS: This study was a retrospective comparison of prospective cohorts. The Montreal Children’s Hospital and the Cohen Children’s Medical Center of New York perform prospective surveillance for HA-VRI using standardized definitions that require the presence of symptoms compatible with VRI and virus detection. Cases detected between April 1, 2010, and March 31, 2013, were identified using surveillance databases. Annual incidence rates were calculated, and a generalized estimating equation model was used to assess determinants of HA-VRI rates. RESULTS: The overall HA-VRI rate during the 3-year study period was significantly higher at Montreal Children’s Hospital than that at Cohen Children’s Medical Center of New York (1.91 vs 0.80 per 1000 patient-days, respectively; P < .0001). Overall, the HA-VRI incidence rate was lowest in the neonatal intensive care unit. Rates in the pediatric intensive care, oncology, and medical/surgical units were similar. The most common etiology of HA-VRI at both institutions was rhinovirus (49% of cases), followed by parainfluenza virus and respiratory syncytial virus. Hospitals with less than 50% single rooms had HA-VRI rates 1.33 (95% confidence interval, 1.29–1.37) times higher than hospitals with more than 50% single rooms for a given unit type. CONCLUSIONS: HA-VRI rates were substantial but different among 2 children’s hospitals. Future studies should examine the effect of HA-VRI and evaluate best practices for preventing such infections.


Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19


title: Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China

text: Abstract Importance An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. Methods We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. Results A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge= 117) or non-survivors (in-hospital death=28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. Conclusion We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.


title: Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids

text: Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen-stimulated cytokine-secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme-linked immunospot technology. Numbers of interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)-stimulated IL-10 secreting cells were increased in early SARS but fell during treatment. SAC-induced IL-12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL-6 and tumour necrosis factor-alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti-inflammatory and antiviral therapies in order to limit cytokine impairment.


The Virus that Changed Spain: Impact of COVID-19 on People with HIV


title: Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies

text: Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0164-2) contains supplementary material, which is available to authorized users.


title: Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational Study

text: Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.


Adaptive tourism areas in times of change


title: Suspension culture of Vero cells for the production of adenovirus type 5

text: PURPOSE: Most cell culture processes for viral vaccine production are mainly based on adherent cell culture systems using serum, which are associated with expensive and labor-intensive processes to produce large amounts of viral vaccine strains. In this study, we investigated whether Vero cells could be grown in serum-free and shaking suspension conditions. Furthermore, we assessed the ability of the Vero cell suspension culture system to produce adenovirus type 5 (Ad5), compared to that of the adhesive Vero cell culture system. MATERIALS AND METHODS: We tested the feasibility of commercial serum-free media for Vero cell culture. For the adaptation of Vero cells in suspension culture, adhesive Vero cells were added in the early phase of shaking suspension culture, and 50 days after shaking suspension culture, suspension-adapted Vero cells were subcultured continuously. To assess the virus production ability of Vero cells in suspension, the cells were infected with Ad5-green fluorescent protein and evaluated based on their fluorescence intensity. RESULTS: The Vero cells grown in OptiPRO serum-free medium showed no changes in morphology and growth rate, but MRC-5 and FRhk-4 cells showed morphological changes and decreased growth rate, respectively. The Vero cells were well adapted to the suspension culture system. The Vero cells in suspension showed a better Ad5 production ability than the adherent Vero cells. CONCLUSION: Vero cells can be grown in OptiPRO serum-free medium. Further, our suspension culture-adapted Vero cells may be suitable to produce viral vaccine strains due to their high ability to produce viruses such as Ad5.


title: Advances in Visualization Tools for Phylogenomic and Phylodynamic Studies of Viral Diseases

text: Genomic and epidemiological monitoring have become an integral part of our response to emerging and ongoing epidemics of viral infectious diseases. Advances in high-throughput sequencing, including portable genomic sequencing at reduced costs and turnaround time, are paralleled by continuing developments in methodology to infer evolutionary histories (dynamics/patterns) and to identify factors driving viral spread in space and time. The traditionally static nature of visualizing phylogenetic trees that represent these evolutionary relationships/processes has also evolved, albeit perhaps at a slower rate. Advanced visualization tools with increased resolution assist in drawing conclusions from phylogenetic estimates and may even have potential to better inform public health and treatment decisions, but the design (and choice of what analyses are shown) is hindered by the complexity of information embedded within current phylogenetic models and the integration of available meta-data. In this review, we discuss visualization challenges for the interpretation and exploration of reconstructed histories of viral epidemics that arose from increasing volumes of sequence data and the wealth of additional data layers that can be integrated. We focus on solutions that address joint temporal and spatial visualization but also consider what the future may bring in terms of visualization and how this may become of value for the coming era of real-time digital pathogen surveillance, where actionable results and adequate intervention strategies need to be obtained within days.


title: Application of a modified loop‐mediated isothermal amplification kit for detecting Norovirus genogroups I and II

text: Norovirus is a major etiologic agent in worldwide outbreaks of gastroenteritis associated with food as well as person‐to‐person transmission. The ubiquitous nature of Norovirus necessitates simple and rapid detection methods with high accuracy and sensitivity. To this end, several investigators have evaluated the usefulness of commercial reverse‐transcription loop‐mediated isothermal amplification (RT‐LAMP) kits for detecting Norovirus genogroups I (GI) and II (GII). In previous studies, the conventional Loopamp kit for Norovirus GII showed a relatively high detection rate, while that for Norovirus GI showed a relatively low detection rate. In the present study, clinical Norovirus specimens were used to compare the detection rate of a modified Loopamp kit for Norovirus GI with the rates of the conventional Loopamp kit for Norovirus GI and an “in‐house” RT‐LAMP GI primer set, methods which had a high detection rate. Results from the present study showed that the modified Loopamp kit for Norovirus GI had a higher detection rate for two viral genotypes (GI.3, GI.11). On comparison with an “in‐house” GII primer set using genotype GII.4 viruses circulating recently, the detection rate by the Loopamp kit for Norovirus GII was found to be higher, with a 98% detection rate. These results indicate the applicability of the modified LAMP kit for GI and the conventional LAMP kit for GII for detection of Noroviruses in clinical samples. J. Med. Virol. 81:2072–2078, 2009. © 2009 Wiley‐Liss, Inc.


title: Replicative capacity of porcine deltacoronavirus and porcine epidemic diarrhea virus in primary bovine mesenchymal cells

text: Abstract Unlike porcine epidemic diarrhea virus (PEDV) that infects only pigs, porcine deltacoronavirus (PDCoV) has the capacity to infect different animal species. In vivo gnotobiotic calves were previously confirmed to be susceptible to infection with PDCoV, but not with PEDV. We next investigated in vitro whether primary bovine cells are susceptible to PDCoV or PEDV infection. We conducted quantification of viral RNA in cell culture supernatants and immunofluorescent staining for the detection of PDCoV or PEDV antigen in two primary bovine cell types inoculated with the PDCoV strain OH-FD22 or PEDV strain PC22-P40 grown in LLC-PK or Vero cells, respectively, and supplemented with 1.25∼5 μg/mL of trypsin in the cell culture medium. The primary cells were isolated from the kidney or heart of a gnotobiotic calf, and both cell types were vimentin-positive, but E-Cadherin-negative, resembling mesenchymal cells. Similar to the previous in vivo observation, cytopathic effects (CPE) that consisted of enlarged and rounded cells, followed by cell shrinkage and detachment, were identified in the two primary cell types inoculated with PDCoV. Unexpectedly, similar CPE was also identified in the two cell types inoculated with PEDV. High PDCoV or PEDV RNA titers and PDCoV or PEDV antigens were detected in the cell culture supernatants and CPE-positive cells, respectively. Our study revealed that primary bovine mesenchymal cells are susceptible to infection with PDCoV and PEDV. The in vitro observation partially coincided with the corresponding in vivo data from gnotobiotic calves.


title: Fungal infections in humans: the silent crisis

text: Annually, over 150 million severe cases of fungal infections occur worldwide, resulting in approximately 1.7 million deaths per year. Alarmingly, these numbers are continuously on the rise with a number of social and medical developments during the past decades that have abetted the spread of fungal infections. Additionally, the long-term therapeutic application and prophylactic use of antifungal drugs in high-risk patients have promoted the emergence of (multi)drug-resistant fungi, including the extremely virulent strain Candida auris. Hence, fungal infections are already a global threat that is becoming increasingly severe. In this article, we underline the importance of more and effective research to counteract fungal infections and their consequences.


title: H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens

text: BACKGROUND: Outbreaks of avian influenza (AI) caused by infection with low pathogenic H9N2 viruses have occurred in poultry, resulting in serious economic losses in Asia and the Middle East. It has been difficult to eradicate the H9N2 virus because of its low pathogenicity, frequently causing in apparent infection. It is important for the control of AI to assess whether the H9N2 virus acquires pathogenicity as H5 and H7 viruses. In the present study, we investigated whether a non-pathogenic H9N2 virus, A/chicken/Yokohama/aq-55/2001 (Y55) (H9N2), acquires pathogenicity in chickens when a pair of di-basic amino acid residues is introduced at the cleavage site of its HA molecule. RESULTS: rgY55sub (H9N2), which had four basic amino acid residues at the HA cleavage site, replicated in MDCK cells in the absence of trypsin after six consecutive passages in the air sacs of chicks, and acquired intravenous pathogenicity to chicken after four additional passages. More than 75% of chickens inoculated intravenously with the passaged virus, rgY55sub-P10 (H9N2), died, indicating that it is pathogenic comparable to that of highly pathogenic avian influenza viruses (HPAIVs) defined by World Organization for Animal Health (OIE). The chickens inoculated with the virus via the intranasal route, however, survived without showing any clinical signs. On the other hand, an avirulent H5N1 strain, A/duck/Hokkaido/Vac-1/2004 (Vac1) (H5N1), acquired intranasal pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the HA, followed by two passages by air sac inoculation in chicks. CONCLUSION: The present results demonstrate that an H9N2 virus has the potential to acquire intravenous pathogenicity in chickens although the morbidity via the nasal route of infection is lower than that of H5N1 HPAIV.


title: China’s ongoing battle against the coronavirus: Why did the lockdown strategy work well?

text: “Why did the lockdown strategy work well in China’s ongoing battle against the coronavirus pandemic?”is one of the three questions the journal editor Wei-Ning Xiang asked us to respond to from our experiences in the past several months since December 2019. At this critical juncture when the people in China are progressing on the battleground, we dedicate this communication essay to all the people fighting against the pandemic around the world.


title: Reducing Social Isolation of Seniors during COVID-19 through Medical Student Telephone Contact

text: Abstract Social isolation has been associated with many adverse health outcomes in older adults. We describe a phone call outreach program in which health care professional student volunteers phoned older adults, living in long-term care facilities and the community, at risk of social isolation during the COVID-19 pandemic. Conversation topics were related to coping, including fears/insecurities, isolation, and sources of support; health; and personal topics such as family and friends, hobbies, and life experiences. Student volunteers felt the calls were impactful both for the students and for the seniors, and call recipients expressed appreciation for receiving the calls and for the physicians who referred them for a call. This phone outreach strategy is easily generalizable, and can be adopted by medical schools to leverage students to connect to socially-isolated seniors in numerous settings.


COVID-19 Pneumonia Hospitalizations Followed by Re-presentation for Presumed Thrombotic Event


title: A history of the therapeutic use of liquorice in Europe

text: Abstract Liquorice root has been used in Europe since prehistoric times, and is well documented in written form starting with the ancient Greeks. In this review we compare the independent development of medical uses of this botanical drug in several ancient cultures, attempting to show the rationality of specific indications across different ethnic groups with different cultural backgrounds. Identical specific indications in different cultures highlight universally reproducible therapeutic effects that are beyond those of a mere placebo. In the first part of the review, historical sources dealing with liquorice (Scythian, Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have been considered. In the second part, the historical records of diseases treated with liquorice have been presented. Finally, a comparison between traditional use in and outside Europe, with the most important recent scientific studies concerning its use, is presented.


title: Variability and Diversity of Nasopharyngeal Microbiota in Children: A Metagenomic Analysis

text: The nasopharynx is the ecological niche for many commensal bacteria and for potential respiratory or invasive pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Disturbance of a balanced nasopharyngeal (NP) microbiome might be involved in the onset of symptomatic infections with these pathogens, which occurs primarily in fall and winter. It is unknown whether seasonal infection patterns are associated with concomitant changes in NP microbiota. As young children are generally prone to respiratory and invasive infections, we characterized the NP microbiota of 96 healthy children by barcoded pyrosequencing of the V5–V6 hypervariable region of the 16S-rRNA gene, and compared microbiota composition between children sampled in winter/fall with children sampled in spring. The approximately 1000000 sequences generated represented 13 taxonomic phyla and approximately 250 species-level phyla types (OTUs). The 5 most predominant phyla were Proteobacteria (64%), Firmicutes (21%), Bacteroidetes (11%), Actinobacteria (3%) and Fusobacteria (1,4%) with Moraxella, Haemophilus, Streptococcus, Flavobacteria, Dolosigranulum, Corynebacterium and Neisseria as predominant genera. The inter-individual variability was that high that on OTU level a core microbiome could not be defined. Microbiota profiles varied strongly with season, with in fall/winter a predominance of Proteobacteria (relative abundance (% of all sequences): 75% versus 51% in spring) and Fusobacteria (absolute abundance (% of children): 14% versus 2% in spring), and in spring a predominance of Bacteroidetes (relative abundance: 19% versus 3% in fall/winter, absolute abundance: 91% versus 54% in fall/winter), and Firmicutes. The latter increase is mainly due to (Brevi)bacillus and Lactobacillus species (absolute abundance: 96% versus 10% in fall/winter) which are like Bacteroidetes species generally related to healthy ecosystems. The observed seasonal effects could not be attributed to recent antibiotics or viral co-infection. The NP microbiota of young children is highly diverse and appears different between seasons. These differences seem independent of antibiotic use or viral co-infection.


title: Porcine epidemic diarrhea virus (PEDV) detection and antibody response in commercial growing pigs

text: BACKGROUND: Longitudinal samples from two production sites were used to (1) describe the pattern of PEDV shedding (rRT-PCR) in individual rectal swabs, pen fecal samples, and pen oral fluids (OF); (2) describe the kinetics of PEDV antibody by ELISA (IgA, IgG) testing of pig serum and pen oral fluid samples; and (3) establish cutoffs and performance estimates for PEDV WV ELISAs (IgA, IgG). Site One was PEDV positive; Site Two was PEDV negative. On Site One, pen samples (feces and oral fluids) and pig samples (rectal swabs and sera) were collected both before and after the population was exposed to PEDV. RESULTS: On Site Two, pen oral fluid samples and individual pig serum samples were negative for both PEDV antibody and nucleic acid. On Site One, PEDV was detected by rRT-PCR at 6 days post exposure (DPE) in all sample types. The last rRT-PCR positives were detected in rectal swabs and oral fluids on 69 DPE. IgG and IgA were detected in oral fluids and serum samples by 13 DPE. Analysis of the PEDV serum IgG WV ELISA data showed that a sample-to-positive (S/P) cutoff of ≥ 0.80 provided a diagnostic sensitivity of 0.87 (95 % CI: 0.82, 0.91) and specificity of 0.99 (95 % CI: 0.98, 1.00). Serum IgG results declined slowly over the monitoring period, with 60 % of serum samples positive (S/P ≥ 0.80) at the final sampling on 111 DPE. Analysis of the PEDV oral fluid IgA WV ELISA found that a cutoff of S/P ≥ 0.80 provided a diagnostic sensitivity of 1.00 (95 % CI: 0.92, 1.00) and a diagnostic specificity of 1.00 (95 % CI: 0.99, 1.00). The oral fluid IgA response increased through 96 DPE and began to decline at the last sampling on 111 DPE. CONCLUSIONS: This study showed that oral fluid-based testing could provide an easy and “animal-friendly” approach to sample collection for nucleic acid and/or antibody-based surveillance of PEDV in swine populations.


title: New Insights in Recurrent HCV Infection after Liver Transplantation

text: Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.


title: Alignment-free prediction of mycobacterial DNA promoters based on pseudo-folding lattice network or star-graph topological indices

text: Abstract The importance of the promoter sequences in the function regulation of several important mycobacterial pathogens creates the necessity to design simple and fast theoretical models that can predict them. This work proposes two DNA promoter QSAR models based on pseudo-folding lattice network (LN) and star-graphs (SG) topological indices. In addition, a comparative study with the previous RNA electrostatic parameters of thermodynamically-driven secondary structure folding representations has been carried out. The best model of this work was obtained with only two LN stochastic electrostatic potentials and it is characterized by accuracy, selectivity and specificity of 90.87%, 82.96% and 92.95%, respectively. In addition, we pointed out the SG result dependence on the DNA sequence codification and we proposed a QSAR model based on codons and only three SG spectral moments.


title: Sampling for Global Epidemic Models and the Topology of an International Airport Network

text: Mathematical models that describe the global spread of infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) often consider a sample of international airports as a network supporting disease spread. However, there is no consensus on how many cities should be selected or on how to select those cities. Using airport flight data that commercial airlines reported to the Official Airline Guide (OAG) in 2000, we have examined the network characteristics of network samples obtained under different selection rules. In addition, we have examined different size samples based on largest flight volume and largest metropolitan populations. We have shown that although the bias in network characteristics increases with the reduction of the sample size, a relatively small number of areas that includes the largest airports, the largest cities, the most-connected cities, and the most central cities is enough to describe the dynamics of the global spread of influenza. The analysis suggests that a relatively small number of cities (around 200 or 300 out of almost 3000) can capture enough network information to adequately describe the global spread of a disease such as influenza. Weak traffic flows between small airports can contribute to noise and mask other means of spread such as the ground transportation.


title: Seamless cloning and gene fusion

text: Gene fusion technology is a key tool in facilitating gene function studies. Hybrid molecules in which all the components are joined precisely, without the presence of intervening and unwanted extraneous sequences, enable accurate studies of molecules and the characterization of individual components. This article reviews situations in which seamlessly fused genes and proteins are required or desired and describes molecular approaches that are available for generating these hybrid molecules.


Increasing HIV prevention and care for injecting drug users


title: Identification of Small‐Molecule Inhibitors of the XendoU Endoribonucleases Family

text: The XendoU family of enzymes includes several proteins displaying high sequence homology. The members characterized so far are endoribonucleases sharing similar biochemical properties and a common architecture in their active sites. Despite their similarities, these proteins are involved in distinct RNA‐processing pathways in different organisms. The amphibian XendoU participates in the biosynthesis of small nucleolar RNAs, the human PP11 is supposed to play specialized roles in placental tissue, and NendoU has critical function in coronavirus replication. Notably, XendoU family members have been implicated in human pathologies such as cancer and respiratory diseases: PP11 is aberrantly expressed in various tumors, while NendoU activity has been associated with respiratory infections by pathogenic coronaviruses. The present study is aimed at identifying small molecules that may selectively interfere with these enzymatic activities. Combining structure‐based virtual screening and experimental approaches, we identified four molecules that specifically inhibited the catalytic activity of XendoU and PP11 in the low micromolar range. Moreover, docking experiments strongly suggested that these compounds might also bind to the active site of NendoU, thus impairing the catalytic activity essential for the coronavirus life cycle. The identified compounds, while allowing deep investigation of the molecular functions of this enzyme family, may also represent leads for the development of new therapeutic tools.


L’évolution du rôle de la SOGC face à la pandémie de COVID-19


title: Alpha-Helical Peptide Assemblies Giving New Function to Designed Structures

text: The design of alpha-helical tectons for self-assembly is maturing as a science. We have now reached the point where many different coiled-coil topologies can be reliably produced and validated in synthetic systems and the field is now moving on towards more complex, discrete structures and applications. Similarly the design of infinite or fiber assemblies has also matured, with the creation fibers that have been modified or functionalized in a variety of ways. This chapter discusses the progress made in both of these areas as well as outlining the challenges still to come.


title: Considerations for Statin Therapy in Patients with COVID‐19

text: Current coronavirus pandemic named coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is the third coronavirus outbreak during the current century after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses.1 Acute respiratory distress syndrome (ARDS) is an immunopathologic event and main cause of death following COVID-19. The main mechanism of ARDS is uncontrolled systemic inflammatory response and cytokine storm following release of proinflammatory cytokines (such as interferons (IFN), interleukines (IL), tumor necrosis factor (TNF)-α) and chemokines.2-3 So, some Chinese researchers proposed or used anti-inflammatory agents in the treatment regimen of patients with COVID-19.3-4.


title: Global Public Health Surveillance under New International Health Regulations

text: The new International Health Regulations adopted by the World Health Assembly in May 2005 (IHR 2005) represents a major development in the use of international law for public health purposes. One of the most important aspects of IHR 2005 is the establishment of a global surveillance system for public health emergencies of international concern. This article assesses the surveillance system in IHR 2005 by applying well-established frameworks for evaluating public health surveillance. The assessment shows that IHR 2005 constitutes a major advance in global surveillance from what has prevailed in the past. Effectively implementing the IHR 2005 surveillance objectives requires surmounting technical, resource, governance, legal, and political obstacles. Although IHR 2005 contains some provisions that directly address these obstacles, active support by the World Health Organization and its member states is required to strengthen national and global surveillance capabilities.


title: Development of a real-time RT-PCR method for detection of porcine rubulavirus (PoRV-LPMV)

text: Abstract In order to provide a rapid and sensitive method for detection of the Porcine rubulavirus La Piedad-Michoacan-Mexico Virus (PoRV-LPMV), we have developed a specific real-time reverse transcriptase polymerase chain reaction assay. The detection of PoRV-LPMV, represents a diagnostic challenge due to the viral RNA being present in very small amounts in tissue samples. In this study, a TaqMan® real-time PCR assay was designed based on the phosphoprotein gene of PoRV-LPMV, to allow specific amplification and detection of viral RNA in clinical samples. Assay conditions for the primers and probe were optimized using infected PK15 cells and ten-fold serial dilutions of a plasmid containing the whole P-gene. The sensitivity of the developed TaqMan® assay was approximately 10 plasmid copies per reaction, and was shown to be 1000 fold better than a conventional nested RT-PCR. The performance of this real-time RT-PCR method enables studies of various aspects of PoRV-LPMV infection. Finally, the assay detects all current known variants of the virus.


title: Customer relationship management systems (CRMS) in the healthcare environment: A systematic literature review

text: Abstract Customer relationship management (CRM) is an innovative technology that seeks to improve customer satisfaction, loyalty, and profitability by acquiring, developing, and maintaining effective customer relationships and interactions with stakeholders. Numerous researches on CRM have made significant progress in several areas such as telecommunications, banking, and manufacturing, but research specific to the healthcare environment is very limited. This systematic review aims to categorise, summarise, synthesise, and appraise the research on CRM in the healthcare environment, considering the absence of coherent and comprehensive scholarship of disparate data on CRM. Various databases were used to conduct a comprehensive search of studies that examine CRM in the healthcare environment (including hospitals, clinics, medical centres, and nursing homes). Analysis and evaluation of 19 carefully selected studies revealed three main research categories: (i) social CRM ‘eCRM’; (ii) implementing CRMS; and (iii) adopting CRMS; with positive outcomes for CRM both in terms of patients relationship/communication with hospital, satisfaction, medical treatment/outcomes and empowerment and hospitals medical operation, productivity, cost, performance, efficiency and service quality. This is the first systematic review to comprehensively synthesise and summarise empirical evidence from disparate CRM research data (quantitative, qualitative, and mixed) in the healthcare environment. Our results revealed that substantial gaps exist in the knowledge of using CRM in the healthcare environment. Future research should focus on exploring: (i) other potential factors, such as patient characteristics, culture (of both the patient and hospital), knowledge management, trust, security, and privacy for implementing and adopting CRMS and (ii) other CRM categories, such as mobile CRM (mCRM) and data mining CRM.


title: Serologic Evidence for MERS-CoV Infection in Dromedary Camels, Punjab, Pakistan, 2012–2015

text: Dromedary camels from Africa and Arabia are an established source for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infection among humans. In Pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of MERS-CoV to Asia.


Human security and universal health insurance


title: A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV, and MERS-CoV

text: The recent outbreak of coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.


title: Social‐economic impact of COVID‐19 pandemic on aesthetic centers in Greece

text: BACKGROUND: Epidemics are a major cause of health problems in developing countries, preventing the accumulation of human capital and economic growth. On the appearance of the pandemic of the new coronavirus COVID‐19 worldwide, this survey was carried out in the 4th week of the occurrence of the cases in Greece. OBJECTIVES: The investigation was aimed at the social and economic impact caused by this COVID‐19 pandemic and the state's decision to suspend the operation of businesses and stores in Greece. MATERIALS AND METHODS: One hundred and fifth‐eight aesthetic centers from various areas of Greece were participated in this study, and the questionnaires were sent electronically to the business owners. Statistical analyzes were conducted using Google Forms and the questionnaires analyzed through PSPP software. RESULTS: Based on their answers and the statistical analyzes, it was calculated the reduction of the monthly income for the first month of suspension of the operation of their companies. Additionally, social related matters were examined as, how they experience this period, psychologically, financially, what problems they believe that they will face and what changes in their work that could result from the pandemic. DISCUSSION: There is no similar study and experience for aesthetic centers from a viral pandemic in literature. The suspension of operations provoked serious financial problems and significant psychological burden about what “tomorrow will bring” with returning to “normalcy”.


Body Temperature Measurement to Prevent Pandemic COVID-19 in Hospitals in Taiwan: Repeated Measurement is Necessary


title: Knowledge, Attitudes and Behaviours of Healthcare Workers in the Kingdom of Saudi Arabia to MERS Coronavirus and Other Emerging Infectious Diseases

text: Background: The Kingdom of Saudi Arabia has experienced a prolonged outbreak of Middle East Respiratory Syndrome (MERS) coronavirus since 2012. Healthcare workers (HCWs) form a significant risk group for infection. Objectives: The aim of this survey was to assess the knowledge, attitudes, infection control practices and educational needs of HCWs in the Kingdom of Saudi Arabia to MERS coronavirus and other emerging infectious diseases. Methods: 1500 of HCWs from Saudi Ministry of Health were invited to fill a questionnaire developed to cover the survey objectives from 9 September 2015 to 8 November 2015. The response rate was about 81%. Descriptive statistics was used to summarise the responses. Results: 1216 HCWs were included in this survey. A total of 56.5% were nurses and 22% were physicians. The most common sources of MERS-coronavirus (MERS-CoV) information were the Ministry of Health (MOH) memo (74.3%). Only (47.6%) of the physicians, (30.4%) of the nurses and (29.9%) of the other HCWs were aware that asymptomatic MERS-CoV was described. Around half of respondents who having been investigated for MERS-CoV reported that their work performance decreased while they have suspicion of having MERS-CoV and almost two thirds reported having psychological problems during this period. Almost two thirds of the HCWs (61.2%) reported anxiety about contracting MERS-CoV from patients. Conclusions: The knowledge about emerging infectious diseases was poor and there is need for further education and training programs particularly in the use of personal protective equipment, isolation and infection control measures. The self-reported infection control practices were sub-optimal and seem to be overestimated.


title: 2019 Novel coronavirus infection and gastrointestinal tract

text: Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. As of Feb 17th, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 75114 confirmed cases, with 2239 deaths. Different from SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) infection, the initial presentations or the chief complain of some patients with the 2019 novel coronavirus (COVID-19) were gastrointestinal symptoms. So we call upon all the first-line medical staff to be cautious and pay more attention to those untypical patients especially from the epidemic area. Besides, as the viral nucleic acids could be found in the fecal samples and anal swabs of some patients with COVID-19 infection, the possibility of fecal-oral transmission need to be took into account. Based on the previously and recently studies, we speculate that COVID-19 may have some relationship with the gut microbiota through angiotensin-converting enzyme 2 (ACE2) receptor, thus targeting gut microbiota might be a new therapeutic option for the treatment of virus-related pneumonia. This article is protected by copyright. All rights reserved.


title: Alteration of immunological parameters in Infectious Bronchitis vaccinated-specific pathogen free broilers after the use of different Infectious Bursal Disease vaccines

text: The vaccines currently available to control infectious bursal disease (IBD) include live-attenuated and inactivated vaccines, immune-complex vaccines and vaccines consisting of viral constructs of herpesvirus of turkeys (HVT) genetically engineered in order to express VP2 surface protein. In order to evaluate the impact of vaccines on the chicken immune system, two animal trials were performed in Specific Pathogen Free (SPF) broiler chickens. In trial 1 birds were either vaccinated at one day-old with a dual rHVT construct vaccine, expressing VP2 protein of IBDV and F protein of Newcastle disease virus, or an immune-complex IBDV vaccine or birds were not vaccinated. At 14, 28 and 35 days, the bursas of Fabricius were collected for bursa:body weight (B:BW) ratio calculation. In trial 2, birds were vaccinated at one-day old according to the same protocol as trial 1, but at day 14 all groups also received a live infectious bronchitis (IB) vaccine. At 0, 7, 14, 21 and 28-days post IB vaccination, birds were tested by ELISA for IB serology, and, soon after the last blood sampling, they were euthanized for collection of Harderian glands, trachea and spleen and testing by flow cytometry for characterization of mononuclear cells. The immune-complex vaccine groups showed significantly lower B:BW ratio, lower IBV antibody titers and higher mean percentage of CD8+ T cells in spleen, trachea and Harderian glands when compared to the other experimental groups. The results of the in vivo trials coupled with a depth analysis of the repertoire of parameters involved in the immune response to IBD and IB vaccinations show as one vaccine may influence the immune response of other vaccines included in the vaccination program.


Anakinra in COVID-19: important considerations for clinical trials


title: Epidemiology characteristics of respiratory viruses found in children and adults with respiratory tract infections in southern China

text: Summary Background The World Health Organization (WHO) ranks respiratory tract infection (RTI) as the second leading cause of death worldwide for children under 5 years of age. The aim of this work was to evaluate the epidemiology characteristics of respiratory viruses found in children and adults with RTI from July 2009 to June 2012 in southern China. Methods In this work, a total of 14 237 nasopharyngeal swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory viruses (influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were detected using PCR/RT-PCR from nasopharyngeal swabs. Results The demographic characteristics, viral prevalence, age distribution, seasonal distribution, and pathogen spectrum of the patients with RTIs were analyzed. Co-infection was observed in 483 specimens, but it was more common in male patients, inpatients, children, and young adults. It varied by season, being more prevalent in the spring and summer and less so in the winter. Human coronavirus and human bocavirus were the most common pathogens, tending to occur in co-infection with other respiratory viruses. Conclusions This work adds to our knowledge of the epidemiology characteristics of these seven common respiratory viruses among patients with RTI in southern China. The detection of the specific viral causes of infection provides a useful starting point for an understanding of illness attributable to respiratory infection, and might also provide data relevant to the development of prevention strategies.


Endo-COVID-19: la risposta delle Scuole di Endocrinologia e Malattie del Metabolismo Italiane alla pandemia da SARS-COV2


COVID-19 and its implications in dental care management against bioaerosol transmission


title: On the electrification of road transportation – A review of the environmental, economic, and social performance of electric two-wheelers

text: Abstract Electrification is widely considered as a viable strategy for reducing the oil dependency and environmental impacts of road transportation. In pursuit of this strategy, most attention has been paid to electric cars. However, substantial, yet untapped, potentials could be realized in urban areas through the large-scale introduction of electric two-wheelers. Here, we review the environmental, economic, and social performance of electric two-wheelers, demonstrating that these are generally more energy efficient and less polluting than conventionally-powered motor vehicles. Electric two-wheelers tend to decrease exposure to pollution as their environmental impacts largely result from vehicle production and electricity generation outside of urban areas. Our analysis suggests that the price of e-bikes has been decreasing at a learning rate of 8%. Despite price differentials of 5000±1800EUR2012 kWh−1 in Europe, e-bikes are penetrating the market because they appear to offer an apparent additional use value relative to bicycles. Mid-size and large electric two-wheelers do not offer such an additional use value compared to their conventional counterparts and constitute niche products at price differentials of 700±360EUR2012 kW−1 and 160±90EUR2012 kW−1, respectively. The large-scale adoption of electric two-wheelers can reduce traffic noise and road congestion but may necessitate adaptations of urban infrastructure and safety regulations. A case-specific assessment as part of an integrated urban mobility planning that accounts, e.g., for the local electricity mix, infrastructure characteristics, and mode-shift behavior, should be conducted before drawing conclusions about the sustainability impacts of electric two-wheelers.


title: Report of 5 nurses infecting COVID-19 during patient care: case Series

text: Abstract Background The high prevalence of COVID-19 has been paied lots of attention all over the world. Nurses are in the first line against this infection and they placed in a high-risk situation. This study aimed to report COVID-19 infection during patients care among nures in the Mostafa Khomini Hospital, Ilam, Iran. In this hospital 125 nurses were enrolled in COVID-19 center. Findings In the present study 5 out of 125 nurses (4%) who enrolled in COVID-19 infection center, were infected with COVID-19. They were first positive for real-time PCR but the CT scan was positive for just one of them. None of the infected nurses were hospitalized and all of them preferred to be quarantine at home and receive the necessary care and treatment (Oseltamivir, Azithromycin and Kaletra. Conclusion This study showed that regardless of self caring, the nurses were exposed to COVID-19. Because at the the beginning of SARS-CoV-2 outbreak in Iran, there were no special protection against this infection.Therfore they were at risk for the COVID-19.This study also reported that receiving the necessary care and treatment at home was a good experience for nurses that can be used in some cases.


title: The Leaf Extracts of Toona sinensis and Fermented Culture Broths of Antrodia camphorata Synergistically Cause Apoptotic Cell Death in Promyelocytic Leukemia Cells

text: Toona sinensis is a common edible vegetable that is used in certain Chinese dishes and has importance in folk medicine. The leaf extracts of T sinensis possess and exhibit anticancer efficacy against various cancer cell types. In Taiwanese folklore, Antrodia camphorata, also known as “Niu-Cheng-Zi,” is used in traditional medicine to treat various illnesses. Its fruit and mycelium possess various potent antiproliferative properties. Two studies from our group have reported that T sinensis or A camphorata has the ability to cause apoptosis in various cancer cells. Conversely, underlying molecular mechanisms and any beneficial effects remain unknown. This study shows anticancer efficacy for both T sinensis and A camphorata co-treatments that target HL-60 cells. The combination index values indicate that 40 µg/mL of T sinensis and 25 µg/mL of A camphorata as a combined treatment shows a synergetic effect, which reduces HL-60 cell proliferation. Alternately, this treatment exhibited no cytotoxic effects for human umbilical vein endothelial cells. Western blot data showed that T sinensis and A camphorata as a combined treatment result in augmented expression of apoptosis, cytochrome c release, Bcl-2 inhibition, expression of Bax, Fas, and FasL, as well as the cleavage of Bid in HL-60 cells. Moreover, this combined treatment overshadowed monotherapy in its ability to inhibit uPAR, MMP-9, MMP-2, COX-2 expression, and PGE(2) secretions. Our study strongly implies that this combined treatment offers more beneficial effects to suppress and treat leukemia due to apoptosis-mediated cell inhibition. Further in vivo studies related to the combined treatment could establish its future potential.


title: Food supply chains during the COVID‐19 pandemic

text: This paper provides an early assessment of the implications of the COVID‐19 pandemic for food supply chains and supply chain resilience. The effects of demand‐side shocks on food supply chains are discussed, including consumer panic buying behaviors with respect to key items, and the sudden change in consumption patterns away from the food service sector to meals prepared and consumed at home. Potential supply‐side disruptions to food supply chains are assessed, including labor shortages, disruptions to transportation networks, and “thickening” of the Canada–U.S. border with respect to the movement of goods. Finally, the paper considers whether the COVID‐19 pandemic will have longer‐lasting effects on the nature of food supply chains, including the growth of the online grocery delivery sector, and the extent to which consumers will prioritize “local” food supply chains.


title: Discovery and Characterization of Novel RNA Viruses in Aquatic North American Wild Birds

text: Wild birds are recognized viral reservoirs but our understanding about avian viral diversity is limited. We describe here three novel RNA viruses that we identified in oropharyngeal/cloacal swabs collected from wild birds. The complete genome of a novel gull metapneumovirus (GuMPV B29) was determined. Phylogenetic analyses indicated that this virus could represent a novel avian metapneumovirus (AMPV) sub-group, intermediate between AMPV-C and the subgroup of the other AMPVs. This virus was detected in an American herring (1/24, 4.2%) and great black-backed (4/26, 15.4%) gulls. A novel gull coronavirus (GuCoV B29) was detected in great black-backed (3/26, 11.5%) and American herring (2/24, 8.3%) gulls. Phylogenetic analyses of GuCoV B29 suggested that this virus could represent a novel species within the genus Gammacoronavirus, close to other recently identified potential novel avian coronaviral species. One GuMPV–GuCoV co-infection was detected. A novel duck calicivirus (DuCV-2 B6) was identified in mallards (2/5, 40%) and American black ducks (7/26, 26.9%). This virus, of which we identified two different types, was fully sequenced and was genetically closest to other caliciviruses identified in Anatidae, but more distant to other caliciviruses from birds in the genus Anas. These discoveries increase our knowledge about avian virus diversity and host distributions.


title: Assessing the Real-Time Mental Health Challenges of COVID-19 in Individuals With Serious Mental Illnesses: Protocol for a Quantitative Study

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused significant stress and mental health problems among the general public. However, persons at greatest risk for poor mental health outcomes, such as people with serious mental illness, have been largely overlooked. OBJECTIVE: This paper presents the protocol for a study that aims to examine the mental health impact of COVID-19 and social distancing behaviors in people with serious mental illness and the behaviors undertaken to prevent COVID-19 infection in this group. METHODS: Participants will include individuals with serious mental illness (eg, schizophrenia, bipolar disorder) and nonpsychiatric control participants who are currently participating in or have previously participated in several ongoing parent observational studies. Data will be collected from April 2020 through August 2020. Participants will complete phone interviews at 2 time points to assess their current emotional functioning and discuss the measures they have taken to prevent COVID-19 infection. Baseline (pre-COVID-19) mental health, sampled by ecological momentary assessment over an extended period, will be compared with current mental health, also sampled by ecological momentary assessment over an extended period. Demographic, cognitive, and psychosocial factors at baseline will be used to examine risk and resilience to current mental health and coping. RESULTS: The inclusion of participants for the first round of telephone assessments started on April 3, 2020 and will be completed by May 31, 2020. As of April 30, 2020, 101 individuals had completed these first-round assessments. The second round of telephone assessments will likely occur between June 1, 2020, and August 31, 2020. Study results will be published in peer-reviewed scientific journals. CONCLUSIONS: Our findings will have broad implications for understanding the psychological consequences of COVID-19 among vulnerable persons with serious mental illness and will provide the opportunity to identify targets to reduce negative outcomes in the future. We also hope our efforts will provide a roadmap and resources for other researchers who would like to implement a similar approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19203


title: Bovine coronaviruses from the respiratory tract: Antigenic and genetic diversity

text: Abstract BoCV isolated from respiratory tract, nasal swab and broncho alveolar washing fluid samples were evaluated for genetic and antigenic differences. These BoCV from the respiratory tract of healthy and clinically ill cattle with BRD signs were compared to reference and vaccine strains based on Spike protein coding sequences and VNT using convalescent antisera. Based on this study, the BoCV isolates belong to one of two genomic clades (clade 1 and 2) which can be differentiated antigenically. The respiratory isolates from Oklahoma in this study were further divided by genetic differences into three subclades, 2a, 2b, and 2c. Reference enteric BoCV strains and a vaccine strain were in clade 1. Currently available vaccines designed to control enteric disease are based on viruses from one clade while viruses isolated from respiratory tracts, in this study, belong to the other clade.


title: The potential of wastewater-based epidemiology as surveillance and early warning of infectious disease outbreaks

text: Infectious diseases caused by pathogens have become one of the main threats to public health. Efficient monitoring of infectious disease transmission is critical to prevent and manage infectious disease epidemics. Wastewater-based epidemiology (WBE) is an efficient approach with great potential for early warning of infectious disease transmission and outbreaks. By analysing infectious disease biomarkers in wastewater taken from wastewater collection points, the transmission of infectious diseases in certain areas can be comprehensively monitored in near real time. This short review presents WBE as a surveillance and early warning system for infectious disease outbreaks regarding pathogens with pandemic potential. We also discuss the challenges and perspective of WBE in infectious disease surveillance and early warning.


title: Modulation of Autophagy for Controlling Immunity

text: Autophagy is an essential process that maintains physiological homeostasis by promoting the transfer of cytoplasmic constituents to autophagolysosomes for degradation. In immune cells, the autophagy pathway plays an additional role in facilitating proper immunological functions. Specifically, the autophagy pathway can participate in controlling key steps in innate and adaptive immunity. Accordingly, alterations in autophagy have been linked to inflammatory diseases and defective immune responses against pathogens. In this review, we discuss the various roles of autophagy signaling in coordinating immune responses and how these activities are connected to pathological conditions. We highlight the therapeutic potential of autophagy modulators that can impact immune responses and the mechanisms of action responsible.


title: P58(IPK): A Novel “CIHD” Member of the Host Innate Defense Response against Pathogenic Virus Infection

text: To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58(IPK), a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2α kinase, PKR. Here, we report that infection of P58(IPK) knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58(IPK) in the antiviral response. Our results suggest that P58(IPK) represents a new class of molecule, a cellular inhibitor of the host defense (CIHD), as P58(IPK) is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.


Pregnancy and Emerging Diseases


title: Unusual presentation of systemic coronavirosis in a ferret

text: Summary A young ferret was presented for a posterior paresis, urinary and fecal incontinence, weight loss, anorexia and lethargy. Biochemichemistry and hematology revealed hyperproteinemia with hyperglobulinemia and anemia. Abdominal ultrasonography showed splenomegaly, adenomegaly and nephromegaly with abdnomal echogenicity of the abdominal organs, compatible with a diagnosis of systemic coronavirosis. The ferret was humanely euthanized. On histopathology, a severe pyogranulomatous inflammation with neutrophilic vasculitis was seen in several organs (kidney, liver, lung, spleen and lymph node). Immunochemistry with FIPV3-70 antibody revealed the presence of coronaviral antigen within the lesions, confirming the diagnosis of Feline Infectious Peritonitis-like disease. A slight mononuclear radiculoneuritis was also present in the sciatic nerve, possibly explaining the peripheral neuropathy observed in this ferret. Whereas posterior paresis is common and non-specific in ferrets, fecal and urinary incontinence are rarely described. Radiculoneuritis caused by systemic coronavirus should be considered in young patients presenting these symptoms.


title: Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs

text: Thiazolides are polypharmacology agents with at least three mechanisms of action against a broad spectrum of parasites, bacteria and viruses. In respiratory viruses they inhibit the replication of orthomyxoviridae and paramyxoviridae at a post-translational level. Nitazoxanide 1a, the prototype thiazolide, was originally developed as an antiparasitic agent and later repurposed for the treatment of viral respiratory infections. The second generation thiazolides following nitazoxanide, such as the 5-chloro analogue RM-5038 2a, are also broad-spectrum antiviral agents as we have reported. Both 1a and its effective circulating metabolite, tizoxanide 1b, are 5-nitrothiazole derivatives, while RM-5038 2a and its de-acetyl derivative RM-4848 2b are the corresponding 5-chloro derivatives. Recently 1a has completed phase II-III clinical trials in the United States, Canada, Australia and New Zealand in a total of 2865 adults and adolescents of at least 12 months of age with viral acute respiratory illness. Since its biodisposition is primarily seen in the gastro-intestinal tract, its efficacy in systemic viral diseases requires relatively high oral doses. The chemical synthesis of new derivatives with a better systemic absorption was therefore urgently needed. In order to improve their systemic absorption, new amino-ester prodrug derivatives of 1b and RM4848 2b were prepared and tested for their animal pharmacology, pharmacokinetics and toxicology. RM-5061 8a in rats showed 7-fold higher blood concentration compared to 1a: absolute bioavailability increased from 3 to 20%, with a good safety profile in animal safety pharmacology and toxicology.


title: The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond

text: Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.


title: Evaluation of a safe and sensitive Spike protein-based immunofluorescence assay for the detection of antibody responses to SARS-CoV

text: Abstract Previously, we have identified a truncated antigenic fragment named protein C [441 to 700 amino acids (a.a.)] as the immunodominant fragment of Spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV). We have now successfully expressed protein C using the baculovirus system in S. frugiperda (Sf-9) cells. This recombinant baculovirus expressing protein C was first characterized using five SARS convalescent human sera and five normal human sera. The results showed that protein C is an authentic antigen against SARS-CoV antibody. Our Spike protein-based immunoflourescence assay (IFA) based on this recombinant baculovirus-Sf-9 system was further assessed with a panel of 163 clinical samples collected during the SARS epidemic in Singapore, which include samples from 21 clinically confirmed SARS, 42 non-SARS patient sera, and 100 normal sera. The results were compared to a commercial SARS IFA kit (EUROIMMUN, Germany) and a conventional IFA test performed in Singapore General Hospital. All of the 21 SARS-positive serum samples could be recognized by our IFA, giving a specificity and sensitivity of 100%, which was compatible with both whole virus-based IFA assays. No cross-reactivity with serum samples against infectious bronchitis virus (IBV) and transmissible gastroenteritis virus (TGEV) were detected in our assays. Thus, our Spike protein-based IFA could offer a safer procedure which can be performed in a BSL-2 laboratory as it could mimic the whole virus based-IFA without any loss of sensitivity and specificity. It is also more user-friendly and cost-effective than the whole virus-based IFA.


title: COVID‐19‐related acute genital ulcers

text: A wide variety of cutaneous manifestations has recently been reported as COVID-19-related skin lesions, such as erythematous rash, acro-ischemia or chilblain-like lesions 1, 2 , which can be useful for the clinical diagnosis of COVID-19. Case reports of other less frequent COVID-19-related skin disorders such as pytiriasis rosea 3 or livedo reticularis 4 have been also described. In order to report a new clinical manifestation of SARS-Coronavirus-2, we present a case of acute reactive genital ulcers in a COVID-19 patient.


title: Surveillance for Newly Emerging Viruses

text: Publisher Summary Surveillance is a fundamental tool for public health, producing information to guide actions. Modern surveillance tends to follow health measures such as the incidence of a disease or syndrome or even the occurrence of health-related behaviors. There are many reasons for conducting surveillance, and the data collected and the approach taken to analyzing those data are both influenced by the overall goal of a surveillance system. Surveillance systems aims mainly at detection also provide information that may be useful for other purposes. The goal of detecting an outbreak of a newly emerging virus, places specific demands on the type of data collected and the types of analysis performed. All approaches to surveillance share some common principles. While some of the underlying methods used in public health surveillance have evolved considerably in recent years, the general approach to surveillance has remained relatively constant. At a fundamental level, surveillance aims to (1) identify individual cases, (2) detect population patterns in identified cases, and then (3) convey information to decision-makers about population health patterns.


title: Type I interferons in viral control and immune regulation

text: Type 1 interferons (IFN-I) exert pleiotropic biological effects during viral infections, all which contribute to balancing virus control and immune pathology. Despite extensive antiviral functions that subdue virus replication, recent studies demonstrate pathogenic and pro-viral roles for IFN-I signaling during acute and persistent virus infection. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses during acute viral infection. In contrast, IFN-I signaling during persistent viral infection supports immune suppression, lymphoid tissue disorganization and CD4 T cell dysfunction. Systematic characterization of the cellular populations and intricacies of IFN-I signaling that promote pathology or immune suppression during acute and persistent viral infections, respectively, should inform the development of treatments and modalities to control viral associated pathologies.


title: Prevalence of Comorbidities Among Individuals With COVID-19: A Rapid Review of current Literature

text: On February 11, 2020 WHO designated the name “COVID-19” for the disease caused by “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), a novel virus that first occurred in Wuhan, China, but quickly turned into a global pandemic. As of June 29, 2020, it has claimed 502,947 lives and is present in more than 213 countries worldwide. Risks associated with acquiring the virus and with its severe outcomes have been reported in various studies, which has led health organizations and governments to develop and institute a variety of preventative and control measures. With constantly growing scientific understanding on this topic, updated information can help equip health and public sectors with the most current knowledge. In this literature review we explore the prevalence of comorbidity among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. Overall, we found that comorbidities including Hypertension (27.4%), Diabetes (17.4%), and Cardiovascular Disease (8.9%) are quite prevalent in COVID-19 patients across major epicenters worldwide and is associated with increased disease severity but not clearly to fatality (OR 0.83, CI[0.60-0.99], p <0.05). Understanding of COVID-19 characteristics and association to common global health problems may provide support and direction to policy makers, clinicians, and researchers in developing shielding strategies to mitigate the COVID-19 pandemic and its severe outcomes.


title: outbreaker2: a modular platform for outbreak reconstruction

text: BACKGROUND: Reconstructing individual transmission events in an infectious disease outbreak can provide valuable information and help inform infection control policy. Recent years have seen considerable progress in the development of methodologies for reconstructing transmission chains using both epidemiological and genetic data. However, only a few of these methods have been implemented in software packages, and with little consideration for customisability and interoperability. Users are therefore limited to a small number of alternatives, incompatible tools with fixed functionality, or forced to develop their own algorithms at considerable personal effort. RESULTS: Here we present outbreaker2, a flexible framework for outbreak reconstruction. This R package re-implements and extends the original model introduced with outbreaker, but most importantly also provides a modular platform allowing users to specify custom models within an optimised inferential framework. As a proof of concept, we implement the within-host evolutionary model introduced with TransPhylo, which is very distinct from the original genetic model in outbreaker, and demonstrate how even complex model results can be successfully included with minimal effort. CONCLUSIONS: outbreaker2 provides a valuable starting point for future outbreak reconstruction tools, and represents a unifying platform that promotes customisability and interoperability. Implemented in the R software, outbreaker2 joins a growing body of tools for outbreak analysis.


title: The Development of an Academic Engagement Intervention for Academically Dismissed Students

text: “Reclaim the W” is an academic recovery program at a medium-sized midwestern university that offers undergraduates who have been academically dismissed a chance to reenroll at the institution. In this article we describe the Reclaim the W program and its target population of academically at-risk undergraduates. We then outline the first two phases of the process we used to develop an intervention for students in the Reclaim the W program, which we call Engage to Excel (E(2)). In the first phase we collected data from focus groups with academically at-risk students and professional staff who serve these students. This qualitative data informed the creation of the E(2) intervention for students in the Reclaim the W program. In the second phase we identified key components of the quasi-experimental E(2) intervention and outlined the student outcomes that will be evaluated during the intervention. Finally, we highlight research and practice implications of the E(2) intervention.


title: Molecular identification of Betacoronavirus in bats from Sardinia (Italy): first detection and phylogeny

text: Bats may be natural reservoirs for a large variety of emerging viruses, including mammalian coronaviruses (CoV). The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in humans, with evidence that these viruses may have their ancestry in bats, highlights the importance of virus surveillance in bat populations. Here, we report the identification and molecular characterization of a bat β-Coronavirus, detected during a viral survey carried out on different bat species in the island of Sardinia (Italy). Cutaneous, oral swabs, and faecal samples were collected from 46 bats, belonging to 15 different species, and tested for viral presence. Coronavirus RNA was detected in faecal samples from three different species: the greater horseshoe bat (Rhinolophus ferrumequinum), the brown long-eared bat (Plecotus auritus), and the European free-tailed bat (Tadarida teniotis). Phylogenetic analyses based on RNA-dependent RNA polymerase (RdRp) sequences assigned the detected CoV to clade 2b within betacoronaviruses, clustering with SARS-like bat CoVs previously reported. These findings point to the need for continued surveillance of bat CoV circulating in Sardinian bats, and extend the current knowledge on CoV ecology with novel sequences detected in bat species not previously described as β-Coronavirus hosts.