title: Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014

text: BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients’ direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180–104 820), i.e., US$ 10 996 (95 % CI, 7 455–16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient’s direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0170-5) contains supplementary material, which is available to authorized users.


Tracheotomy in COVID‐19 patients: preliminary experience and technical refinements


title: Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus

text: Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.


Chilblains‐like dermatologic manifestation of COVID‐19 diagnosed by serology via multidisciplinary virtual care


title: Chronique d’une kinésithérapeute à l’heure de la Covid-191

text: Résumé Ce récit témoigne du vécu de l’épidémie à l’heure de la Covid-19, par l’auteur masseur-kinésithérapeute en service hospitalier et en libéral. Après un descriptif de son expérience dans les différentes dimensions de sa vie, professionnelle et personnelle, l’auteur éclaire son ressenti de notions psychologiques et philosophiques. Abstract This story is a testimony to the experience of the epidemic at the time of Covid-19, by the author, a physiotherapist in hospital service and in liberal. After describing his experience in the various dimensions of his life, professional and personal, the author clarifies his feelings with psychological and philosophical notions.


title: Antibiotic Discontinuation Rates Associated with Positive Respiratory Viral Panel and Low Procalcitonin Results in Proven or Suspected Respiratory Infections

text: INTRODUCTION: The differentiation of viral from bacterial pneumonia is important in determining whether antibiotics are appropriate for treatment of these infections. Advances in diagnostic technologies such as respiratory panels (RP) utilizing polymerase chain reactions to detect viruses and determination of procalcitonin (PCT) concentrations may aid in this differentiation. However, some studies have shown limited impact for this purpose and thus continuation of antibiotics despite results suggesting viral infection. Our objective was to characterize clinician-prescribing behavior at our institution once RP and/or PCT results were known and suggestive of a viral respiratory infection. METHODS: This retrospective analysis was based upon records of hospitalized patients in whom proven or possible respiratory infections as indicated by RP testing, respiratory bacterial culture or International Statistical Classification of Diseases and Related Health Problems 9th revision codes for acute infectious respiratory illness was documented. Patients evaluated were required to have a RP or PCT within the first 72 h of presentation. Drug orders were evaluated for discontinuation of antibiotic therapy within 48 h of a procalcitonin of <0.25 μg/mL, a positive viral RP result, or both. RESULTS: Of 4869 patients with PCT and/or RP results, 2031 were included. PCT and RP testing were obtained in 503 and 1823 patients, respectively, with 295 patients having both. Results of these tests suggested 789 patients were potential candidates for antibiotic avoidance. These included 219 with a PCT <0.25 μg/mL, 601 with a positive viral RP result, and 31 with both. Antibiotics were administered to 307 patients (39%) within the first 72 h. In these, antibiotics were discontinued within 48 h of laboratory results availability. CONCLUSION: These results suggest that positive viral RP and low PCT results are infrequently associated with discontinuation of antibiotic therapy in proven or possible respiratory infections at our institution. Direct interventions with clinicians are likely needed to correct this behavior and decrease unnecessary antibiotic use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0087-5) contains supplementary material, which is available to authorized users.


title: Accumulating evidence for a role of oxidized phospholipids in infectious diseases

text: Oxidized phospholipids (OxPL) were originally discovered as by-products and mediators of chronic inflammation such as in atherosclerosis. Over the last years, an increasing body of evidence led to the notion that OxPL not only contribute to the pathogenesis of chronic inflammatory processes but in addition play an integral role as modulators of inflammation during acute infections. Thereby, host defense mechanisms involve the generation of oxygen radicals that oxidize ubiquitously present phospholipids, which in turn act as danger-associated molecular patterns (DAMPs). These OxPL-derived DAMPs can exhibit both pro- and anti-inflammatory functions that ultimately alter the host response to pathogens. In this review, we summarize the currently available data on the role of OxPL in infectious diseases.


title: SARS-CoV Genome Polymorphism: A Bioinformatics Study

text: A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a “profile”, were determined and discussed ("profile" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.


title: Disordered Residues and Patterns in the Protein Data Bank

text: We created a new library of disordered patterns and disordered residues in the Protein Data Bank (PDB). To obtain such datasets, we clustered the PDB and obtained the groups of chains with different identities and marked disordered residues. We elaborated a new procedure for finding disordered patterns and created a new version of the library. This library includes three sets of patterns: unique patterns, patterns consisting of two kinds of amino acids, and homo-repeats. Using this database, the user can: (1) find homologues in the entire Protein Data Bank; (2) perform a statistical analysis of disordered residues in protein structures; (3) search for disordered patterns and homo-repeats; (4) search for disordered regions in different chains of the same protein; (5) download clusters of protein chains with different identity from our database and library of disordered patterns; and (6) observe 3D structure interactively using MView. A new library of disordered patterns will help improve the accuracy of predictions for residues that will be structured or unstructured in a given region.


title: Protective Effects of Long Pentraxin PTX3 on Lung Injury in a Severe Acute Respiratory Syndrome Model in Mice

text: The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infection s. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in Coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3 deficient mice (129/SvEv/C57BL6/J) and their wild type littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3wild type mice, MHV -1 induced PTX3 expression in the lung and serum in a time dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3 deficient mice than that in wild type mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung; attenuated MHV-1 induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection -induced acute lung injury.


Humanism in the Age of COVID-19: Renewing Focus on Communication and Compassion


title: Optimising Lockdown Policies for Epidemic Control using Reinforcement Learning: An AI-Driven Control Approach Compatible with Existing Disease and Network Models

text: There has been intense debate about lockdown policies in the context of Covid-19 for limiting damage both to health and to the economy. We present an AI-driven approach for generating optimal lockdown policies that control the spread of the disease while balancing both health and economic costs. Furthermore, the proposed reinforcement learning approach automatically learns those policies, as a function of disease and population parameters. The approach accounts for imperfect lockdowns, can be used to explore a range of policies using tunable parameters, and can be easily extended to fine-grained lockdown strictness. The control approach can be used with any compatible disease and network simulation models.


title: The cytokine storm of severe influenza and development of immunomodulatory therapy

text: Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as ‘cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.


title: Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs

text: Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (⩾2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF-1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV.


title: Respiratory Infections during SARS Outbreak, Hong Kong, 2003

text: The effect of community hygienic measures during the outbreak of severe acute respiratory syndrome in Hong Kong was studied by comparing the proportion of positive specimens of various respiratory viruses in 2003 with those from 1998 to 2002. Community hygienic measures significantly reduced the incidence of various respiratory viral infections.


title: Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors

text: The SARS-CoV-2 is the causative agent of COVID-19 pandemic that is causing a global health emergency. The lack of targeted therapeutics and limited treatment options have triggered the scientific community to develop new vaccines or small molecule therapeutics against various targets of SARS-CoV-2. The main protease (Mpro) is a well characterized and attractive drug target because of its crucial role in processing of the polyproteins which are required for viral replication. In order to provide potential lead molecules against the Mpro for clinical use, we docked a set of 65 bioactive molecules of Tea plant followed by exploration of the vast conformational space of protein-ligand complexes by long term molecular dynamics (MD) simulations (1.50 µs). Top three bioactive molecules (Oolonghomobisflavan-A, Theasinensin-D, and Theaflavin-3-O-gallate) were selected by comparing their docking scores with repurposed drugs (Atazanavir, Darunavir, and Lopinavir) against SARS-CoV-2. Oolonghomobisflavan-A molecule showed a good number of hydrogen bonds with Mpro and higher MM-PBSA binding energy when compared to all three repurposed drug molecules. during the time of simulation. This study showed Oolonghomobisflavan-A as a potential bioactive molecule to act as an inhibitor for the Mpro of SARS-CoV-2. [Image: see text] Communicated by Ramaswamy H. Sarma


title: China’s Internationalized Higher Education During Covid-19: Collective Student Autoethnography

text: This article presents 15 autoethnographical texts detailing student experiences at Beijing Normal University in the midst of the Covid-19 pandemic. Contributions have been collected over 6 weeks between 15 February and 1 April 2020, edited by Hejia Wang (assisted by Moses Oladele Ogunniran and Yingying Huang), and supervised by Michael Peters. Through shared in-depth empirical feelings and representations from a wide variety of cultural, historical, and social contexts, the article outlines an answer to the question: How do students, connected virtually but separated physically in an internationalized university, deal with disruption brought about by the Covid-19 pandemic? Student testimonies offer reflections on Covid-19 and Chinese international education, experiences of online teaching and learning, reflections on university coping mechanisms, an account of realities and feelings related to changes in academic life, and discussions on coping strategies in Chinese international higher education. Contributors expose their individual feelings, effects, benefits, challenges, and risk management strategies. Collected at the peak of the Covid-19 pandemic, these testimonies are unable to offer systemic answers to challenges facing the whole world. However, these experiences and feelings will provide important inputs to global discussions about the future of the world, after Covid-19.


title: Mechanism of measles virus failure to activate NF-κB in neuronal cells

text: Lack of IFN-β and MHC class I expression in measles virus (MV) infected neurons could impair the host antiviral defense mechanism and result in virus escape from recognition by cytotoxic T-cells. Induction of IFN-β and MHC class I gene expression requires NF-κB activation which depends on degradation of IκBα, an inhibitory protein of NF-κB. In earlier studies we demonstrated that in contrast to glial cells, MV was unable to induce IκBα degradation in neuronal cells. It is unclear whether this failure is due to the presence of a neuron-specific IκBα isoform or a defect in the MV signaling cascade that leads to IκBα phosphorylation and degradation. In this study, an IκBα-wild type (WT) expression vector was transfected into neuronal and glial cells and subsequently exposed to MV. In contrast to glial cells, IκBα-WT was degraded in neuronal cells in response to TNFα but not MV. The findings eliminate the existence of an IκBα isoform in neuronal cells that is resistant to phosphorylation by MV. Blocking de novo protein synthesis with cyclohexamide had no effect on neuronal IκBα, indicating that lack of degradation rather than increased synthesis is responsible for IκBα accumulation in MV-stimulated neuronal cells. To determine if malfunction in the MV receptor CD46 is responsible for failure of IκBα phosphorylation and degradation, neuronal cells were transfected with a wild type CD46 (CD46-WT) expression vector. MV stimulation of CD46-WT transfected cells failed to induce IκBα degradation. Collectively these findings indicate that failure of MV to phosphorylate neuronal IκBα is not due to a presence of an IκBα isoform or malfunction of the MV receptor, and is more likely to be due to a defect in the signaling pathway that normally leads to IκBα phosphorylation and degradation.


title: Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway

text: Programmed −1 ribosomal frameshift (−1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterized in viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a −1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated −1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA–miRNA interaction suggests that formation of a triplex RNA structure stimulates −1 PRF. A −1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional −1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature13429) contains supplementary material, which is available to authorized users.


title: Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratories

text: Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30–45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories.


title: Precautions in ophthalmic practice in a hospital with a major acute SARS outbreak: an experience from Hong Kong

text: Many new infectious diseases in humans have been derived from animal sources in the past 20 years. Some are highly contagious and fatal. Vaccination may not be available and antiviral drugs are not effective enough. Infectious control is important in clinical medicine and in Ophthalmology. Severe acute respiratory syndrome (SARS), as an example, is a highly contagious respiratory disease that has recently been reported in Asia, North America, and Europe. Within a matter of weeks, the outbreak has evolved to become a global health threat and more than 30 countries have been afflicted with a novel Coronavirus strain (SARS-CoV) that is the aetiologic agent of SARS. The primary route of transmission of SARS appears involving close person-to-person contact through droplets. Ophthalmologists may be particularly susceptible to the infection as routine ophthalmic examinations like direct ophthalmoscopy and slit-lamp examination are usually performed in a setting that has close doctor–patient contact. Being the Ophthalmology Department of the only hospital in the world that has just gone through the largest outbreak of SARS, we would like to share our strategy, measures, and experiences of preventing contracting or spreading of SARS infection as an infection control model. SARS is one of the many viruses against which personnel will need protecting in an ophthalmic setting. The experiences attained and the measures established might also apply to other infectious conditions spreading by droplets such as the avian influenza with H5N1.


title: Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam

text: BACKGROUND: Acute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam. METHODS: Data from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children’s Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs). RESULTS: Over the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May–June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September–October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level. CONCLUSIONS: ARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.


title: Respiratory protection policies and practices among the health care workforce exposed to influenza in New York State: Evaluating emergency preparedness for the next pandemic

text: BACKGROUND: New York State hospitals are required to implement a respiratory protection program (RPP) consistent with the Occupational Safety and Health Administration respirator standard. Guidance provided during the 2009 novel H1N1 pandemic expanded on earlier recommendations, emphasizing the need to keep staff in all health care settings healthy to maintain services. METHODS: New York State hospitals with emergency departments having more than 1,000 visits annually were invited to participate; 23 hospitals participated. Health care workers, unit managers, and hospital managers were interviewed regarding knowledge, beliefs, and practices of respiratory protection. Interviewees were observed donning and doffing an N-95 respirator as they normally would during patient care. Written RPPs for each hospital were evaluated. RESULTS: The majority of the hospitals surveyed had implemented an RPP, although unawareness of the policies and practices, as well as inadequacies in education and training exist among health care workers. CONCLUSION: Health care workers and other hospital employees may be unnecessarily exposed to airborne infectious diseases. Having an RPP ensures safe and effective use of N-95 respirators and will help prevent avoidable exposure to disease during a pandemic, protecting the health care workforce and patients alike.


Lesiones musculoesqueléticas secundarias al ejercicio durante el confinamiento por la pandemia covid-19


title: Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors

text: Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes depending on the cell or tissue type. The virus Spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abl kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titers and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which can make experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titers by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying host cell pathways required for coronavirus infection. This will provide insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.


title: Nuclear cardiology in the COVID-19 pandemic era

text: Summary The current coronavirus disease 2019 (COVID-19) pandemic has important implications for the cardiovascular care of patients. Implementation of a robust plan in nuclear cardiology units is required to prevent further nosocomial spread of the outbreak. This editorial covers the practical advice on how to protect patients and nuclear cardiology staff against COVID-19.


title: Taking the bull by the horns: Ethical considerations in the design and implementation of an Ebola virus therapy trial

text: Abstract Ebola virus is categorized as one of the most dangerous pathogens in the world. Although there is no known cure for Ebola virus, there is some evidence that the severity of the disease can be curtailed using plasma from survivors. Although there is a general consensus on the importance of research, methodological and ethical challenges for conducting research in an emergency situation have been identified. Performing clinical trials is important, especially for health conditions that are of public health significance (including rare epidemics) to develop new therapies as well as to test the efficacy and effectiveness of new interventions. However, routine clinical trial procedures can be difficult to apply in emergency public health crises hence require a consideration of alternative approaches on how therapies in these situations are tested and brought to the market. This paper examines some of the ethical issues that arise when conducting clinical trials during a highly dangerous pathogen outbreak, with a special focus on the Ebola virus outbreak in West Africa. The issues presented here come from a review of a protocol that was submitted to the Global Emerging Pathogens Treatment Consortium (GET). In reviewing the proposal, which was about conducting a clinical trial to evaluate the safety and efficacy of using convalescent plasma in the management of Ebola virus disease, the authors deliberated on various issues, which were documented as minutes and later used as a basis for this paper. The experiences and reflections shared by the authors, who came from different regions and disciplines across Africa, present wide-ranging perspectives on the conduct of clinical trials during a dangerous disease outbreak in a resource-poor setting.


China coronavirus: Hong Kong health staff strike to demand border closure as city records first death.


title: Endemic infection can shape exposure to novel pathogens: Pathogen co‐occurrence networks in the Serengeti lions

text: Pathogens are embedded in a complex network of microparasites that can collectively or individually alter disease dynamics and outcomes. Endemic pathogens that infect an individual in the first years of life, for example, can either facilitate or compete with subsequent pathogens thereby exacerbating or ameliorating morbidity and mortality. Pathogen associations are ubiquitous but poorly understood, particularly in wild populations. We report here on 10 years of serological and molecular data in African lions, leveraging comprehensive demographic and behavioural data to test if endemic pathogens shape subsequent infection by epidemic pathogens. We combine network and community ecology approaches to assess broad network structure and characterise associations between pathogens across spatial and temporal scales. We found significant non‐random structure in the lion‐pathogen co‐occurrence network and identified both positive and negative associations between endemic and epidemic pathogens. Our results provide novel insights on the complex associations underlying pathogen co‐occurrence networks.


Update: Severe Respiratory Illness Associated With a Novel Coronavirus—Worldwide, 2012-2013


Publishing in face of the COVID-19 pandemic


title: Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors

text: The envelope glycoproteins GP1 and GP2 of Lassa virus (LASV) bind to the host cell receptors to mediate viral infection. So far, no approved vaccines and specific treatment options against LASV exist. To develop specific fusion inhibitors against LASV, we solved the crystal structure of the post-fusion 6 helix bundle (6-HB) formed by two heptad repeat domains (HR1 and HR2) of GP2. This fusion core contains a parallel trimeric coiled-coil of three HR1 helices, around which three HR2 helices are entwined in an antiparallel manner. Various hydrophobic and charged interactions form between HR1 and HR2 domains to stabilize the overall conformation of GP2 fusion core. Based on the structure, we designed several peptides spanning the HR2 domain and tested their antiviral activities. We found that the longer HR2 peptides were effective in inhibiting LASV GPC protein-mediated cell–cell fusion under low pH condition. These results not only suggest that LASV infects the target cell mainly through endocytosis, including micropinocytosis, and membrane fusion at low pH, but also provide an important basis for rational design of LASV fusion inhibitors.


Amantadine resistance among influenza A isolates in Sweden 2001–2006


title: Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

text: The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.


title: EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication

text: Abstract Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs, which is correlated with high morbidity and mortality in suckling piglets. Using the method of GST pull-down with the nucleocapsid (N), N protein was found to interact with swine testes (ST) cells elongation factor 1-alpha (EF1A), an essential component of the translational machinery with an important role in cells. In vitro and in virus-infected cells interaction was then confirmed by co-precipitation. Knockdown of EF1A impairs N protein proliferation and TGEV replication in host cell. It was demonstrated that EF1A plays a role in TGEV replication. The present study thus provides a protein-related information that should be useful for underlying mechanism of coronavirus replication.


title: The YXXΦ motif within the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is crucial for its intracellular transport

text: BACKGROUND: The SARS coronavirus (SARS-CoV) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. It is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. However the role of these motifs is not fully understood in the case of 3a protein. METHODS: The subcellular distribution of the 3a protein was studied by immunofluorescence staining of cells transfected with wild type and mutant constructs along with markers for different intracellular compartments. Semi-quantitative RT-PCR was performed to estimate the mRNA where as western blotting was carried out to detect protein levels of wild type and mutant 3a proteins. In vitro transcription- translation was performed to estimate cell free protein synthesis. RESULTS: While the wild type 3a protein is efficiently transported to the plasma membrane, the protein with mutations in the tyrosine and valine residues within the YXXV motif (ΔYXXΦ) accumulated in the Golgi compartment. However the 3a protein with mutations within the EXD di-acidic motif (ΔEXD) showed an intracellular distribution similar to the wild type protein. Increased retention of the ΔYXXΦ protein in the Golgi compartment also increased its association with lipid droplets. The ΔYXXΦ protein also expressed at significantly lower levels compared to the wild type 3a protein, which was reversed with Brefeldin A and Aprotinin. CONCLUSIONS: The data suggest that the YXXΦ motif of the SARS-CoV 3a protein is necessary for Golgi to plasma membrane transport, in the absence of which the protein is targeted to lysosomal degradation compartment via lipid droplets.


title: Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors

text: The current study was designed to assess the inhibitory activity of Broussonetia papyrifera-derived polyphenols against 3-chymotrypsin-like and papain-like coronavirus cysteine proteases. The isolated compounds were broussochalcone B (1), broussochalcone A (2), 4-hydroxyisolonchocarpin (3), papyriflavonol A (4), 3′-(3-methylbut-2-enyl)-3′,4,7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), broussoflavan A (8), kazinol F (9), and kazinol J (10). All polyphenols were more potent against papain-like protease (PL(pro)) than against 3-chymotripsin-like protease (3CL(pro)); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PL(pro) with an IC(50) value of 3.7 μM. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PL(pro) were determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents.


title: Histologic features of long lasting chilblain‐like lesions in a pediatric COVID‐19 patient

text: Since the beginning of the pandemic of Coronavirus disease (COVID‐19) an increasing number of skin manifestations have been reported.(1,2) Most reports concern adult patients and describe various patterns of skin eruptions, in most of cases with low specificity and no univocal temporal association with the onset of systemic symptoms of COVID‐19.(1‐3)


title: Can India develop herd immunity against COVID-19?

text: World Health Organization declared the novel coronavirus disease 2019 (COVID-19) outbreak to be a public health crisis of international concern. Further, it provided advice to the global community that countries should place strong measures to detect disease early, isolate and treat cases, trace contacts and promote “social distancing” measures commensurate with the risk. This study analyses the COVID-19 infection data from the top 15 affected countries in which we observed heterogeneous growth patterns of the virus. Hence, this paper applies multifractal formalism on COVID-19 data with the notion that country-specific infection rates follow a power law growth behaviour. According to the estimated generalized fractal dimension curves, the effects of drastic containment measures on the pandemic in India indicate that a significant reduction of the infection rate as its population is concern. Also, comparison results with other countries demonstrate that India has less death rate or more immunity against COVID-19.


Addressing COVID‐19 fear to improve clinic attendance for patients with wet age‐related macular degeneration


title: An antibody derivative expressed from viral vectors passively immunizes pigs against transmissible gastroenteritis virus infection when supplied orally in crude plant extracts

text: To investigate the potential of antibody derivatives to provide passive protection against enteric infections when supplied orally in crude plant extracts, we have expressed a small immune protein (SIP) in plants using two different plant virus vectors based on potato virus X (PVX) and cowpea mosaic virus (CPMV). The ɛSIP molecule consisted of a single‐chain antibody (scFv) specific for the porcine coronavirus transmissible gastroenteritis virus (TGEV) linked to the ɛ‐CH4 domain from human immunoglobulin E (IgE). In some constructs, the sequence encoding the ɛSIP molecule was flanked by the leader peptide from the original murine antibody at its N‐terminus and an endoplasmic reticulum retention signal (HDEL) at its C‐terminus to allow the expressed protein to be directed to, and retained within, the endoplasmic reticulum. Western blot analysis of samples from Nicotiana clevelandii or cowpea tissue infected with constructs revealed the presence of SIP molecules which retained their ability to dimerize. The analysis of crude plant extracts revealed that the plant‐expressed ɛSIP molecules could bind to and neutralize TGEV in tissue culture, the levels of binding and neutralization reflecting the level of expression. Oral administration of crude extracts from SIP‐expressing plant tissue to 2‐day‐old piglets demonstrated that the extracts which showed the highest levels of in vitro neutralization could also provide in vivo protection against challenge with TGEV.


Addressing Challenges in Obtaining Emergency Medicine Away Rotations and Standardized Letters of Evaluation Due to COVID-19 Pandemic


title: Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus

text: Abstract The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foetuses, stillborn pigs, and dead piglets, indicating that the live vaccine spread from vaccinated piglets to non-vaccinated sows, and that the virus might be implicated in the severe reproductive problems observed. In the present study, one such VDV isolate was used to experimentally infect pregnant sows in the last trimester. The chosen isolate, which had more than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS.


title: Synthesis and in vitro cytostatic activity of new β-d-arabino furan[1′,2′:4,5]oxazolo- and arabino-pyrimidinone derivatives

text: A series of nucleoside derivatives was obtained via heteroatom annulation of the amino oxazoline of d-(−)-arabinose. Unequivocal proofs for the stereostructure of some new arabinosyl pyrimidinone derivatives were obtained by X-ray structure analysis. These newly synthesized compounds were then evaluated for their cytostatic activity against murine leukemia (L1210), and human T-lymphocytes (Molt 4/C8 and CEM). Of all the compounds in the series, the protected silylated tricyclic fused pyrimidinone 10 showed the most significant antitumor activity against murine leukemia L1210 (IC(50) = 6 μM), and human T-lymphocytes cells Molt 4/C8 (IC(50) = 7.9 μM) and CEM/0 cell lines (IC(50) = 7.5 μM). None of the compounds exhibited significant antiviral inhibitory activities.


title: Genetic Variation of SARS Coronavirus in Beijing Hospital

text: To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients.


title: Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID‐19 in Chongqing

text: Mortality is high among severe patients with 2019 novel coronavirus‐infected disease (COVID‐19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID‐19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO(2)/FiO(2) ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3‐6.0). Pulmonary inflammation index, platelet counts, sodium, C‐reactive protein, prealbumin, and PaCO(2) showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7‐0.8). And potassium, creatinine, temperature, and D‐dimer showed mild distinguishing power (each AUC between 0.6‐0.7). In addition, higher C‐reactive protein was associated with shorter time to progress to severe cases (r = −0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID‐19.


title: Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes

text: Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003–2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10(−4) mutations/site/year (95% highest posterior density 4.55 × 10(−4) to 5.38 × 10(−4)) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10(−4) mutations/site/year, 95% highest posterior density 3.26 × 10(−4) to 3.94 × 10(−4)). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.


Lesions pernióticas y acrales en España durante el confinamiento por COVID: análisis retrospectivo de 12 casos


title: Public Health Emergency Response in Taiwan

text: In recent years, growth of international travel and trade, as well as climate change, has resulted in the frequent emergence and reemergence of infectious diseases such as Ebola, Zika, and MERS. In 2016, Taiwan used the Joint External Evaluation (JEE) tool to evaluate its public health emergency response capacities and understand important areas for improvement. This article presents Taiwan's disaster and public health emergency response organizational structure, real-time integrated information, response processes, and command center structure. After reviewing the results of the JEE tool and drawing lessons from emergency response efforts in the United States, we provide 3 recommendations that may enhance Taiwan's public health emergency response capacities: establish common principles for disaster response regardless of which agency is in charge, standardize operation procedures, and perform regular training that includes nongovernmental organizations and a range of government departments.


title: An analysis of COVID-19 spread based on fractal interpolation and fractal dimension

text: The present paper proposes a reconstruction of the epidemic curves from the fractal interpolation point of view. Looking at the epidemic curves as fractal structures might be an efficient way to retrieve missing pieces of information due to insufficient testing and predict the evolution of the disease. A fractal approach of the epidemic curve can contribute to the assessment and modeling of other epidemics. On the other hand, we have considered the spread of the epidemic in countries like Romania, Italy, Spain, and Germany and analyzed the spread of the disease in those countries based on their fractal dimension.


title: Social costs of tourism during the COVID-19 pandemic

text: The severe acute respiratory syndrome coronavirus 2 is currently spreading across the world at an alarming rate, resulting in the coronavirus disease 2019 pandemic. Amidst this crisis, tourism scholars are directing their attention to communities at tourist destinations, looking at their safety and well-being and the costs that they will bear due to the cessation of tourism activity. This article describes residents' perceptions of the risks posed by tourism activity, and estimates their willingness to pay to reduce public health risks based on hypothetical scenarios, using the triple-bounded dichotomous choice contingent valuation method. The social costs in three urban destinations are assessed and compared. Based on the findings, suggestions are made for appropriate post-pandemic recovery actions by local authorities and tourism organizations.


title: Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

text: Abstract Many highly effective vaccines have been produced against viruses whose virulent infection elicits strong and durable protective immunity. In these cases, characterization of immune effector mechanisms and identification of protective epitopes/immunogens has been informative for the development of successful vaccine programs. Diseases in which the immune system does not rapidly clear the acute infection and/or convalescent immunity does not provide highly effective protection against secondary challenge pose a major hurdle for clinicians and scientists. Porcine reproductive and respiratory syndrome virus (PRRSV) falls primarily into this category, though not entirely. PRRSV causes a prolonged infection, though the host eventually clears the virus. Neutralizing antibodies can provide passive protection when present prior to challenge, though infection can be controlled in the absence of detectable neutralizing antibodies. In addition, primed pigs (through natural exposure or vaccination with a modified-live vaccine) show some protection against secondary challenge. While peripheral PRRSV-specific T cell responses have been examined, their direct contribution to antibody-mediated immunity and viral clearance have not been fully elucidated. The innate immune response following PRRSV infection, particularly the antiviral type I interferon response, is meager, but when provided exogenously, IFN-α enhances PRRSV immunity and viral control. Overall, the quality of immunity induced by natural PRRSV infection is not ideal for informing vaccine development programs. The epitopes necessary for protection may be identified through natural exposure or modified-live vaccines and subsequently applied to vaccine delivery platforms to accelerate induction of protective immunity following vaccination. Collectively, further work to identify protective B and T cell epitopes and mechanisms by which PRRSV eludes innate immunity will enhance our ability to develop more effective methods to control and eliminate PRRS disease.


title: Anticoagulation Practice Patterns in COVID‐19: A Global Survey

text: BACKGROUND: Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with SARS‐CoV‐2 disease 2019 (COVID‐19) is unknown due to limited published data in this population. OBJECTIVES: We aimed to assess current global practice and experience in management of COVID‐19 associated coagulopathy to identify information to guide prospective and randomized studies. METHODS: Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID‐19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. RESULTS: 515 physicians responded from 41 countries. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID‐19 with most recommending use of low‐molecular‐weight heparin or unfractionated heparin. Significant practice variation was found regarding need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. 291 respondents reported observing thrombotic complications in their patients with 64% noting that the complication was pulmonary embolism (PE). Of the 44% of respondents that estimated incidence of thrombosis in patients with COVID‐19 in their hospital, estimates ranged widely from 1 to 50%. 174 respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant non‐major bleeding, and 12% major bleeding). CONCLUSION: Well‐designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in COVID‐19 patients. Randomized clinical trials addressing use of anticoagulation are also needed.


title: Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis

text: AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.


title: Detection of hepatitis B virus DNA and HBsAg from postmortem blood and bloodstains

text: A large number of accidental virus infections occur in medical and non-medical workers exposed to infectious individuals and materials. We evaluated whether postmortem blood and bloodstains containing hepatitis B virus (HBV) are infectious. HBV-infected blood and bloodstains were stored for up to 60 days at room temperature and subsequently screened for hepatitis B surface antigen (HBsAg) and HBV DNA. In addition, HBV-positive postmortem blood was added to a cell line and the production of HBV virions was examined over a period of 7 days. HBsAg and HBV DNA were detected in all samples stored for 60 days at room temperature. HBV-positive postmortem blood successfully infected the cell line and progeny viruses were produced for up to 6 days. Thus, it is crucial that due care is taken when handling not only living material infected with HBV, as well as other harmful viruses, but also blood or body fluids from cadavers or medical waste.


title: New Virus, New Challenge

text: The ongoing COVID-19 pandemic has made us to consider the emergence of potential viral diseases in the future. Animals can carry vast and diverse virus species, most of which we do not understand yet, and the spillover events of the viruses from the unknown pool in animals to human population always occurred in the past. To effectively prevent and control the emerging viral diseases, we should make efforts to explore the unknown virus species in nature and prepare in advance.


title: Senior Medical Students in the COVID‐19 Response: An Opportunity to Be Proactive

text: On March 13th, the United States (US) declared the novel coronavirus (COVID-19) pandemic a national emergency. By March 18th , according to the Centers for Disease Control and Prevention, COVID-19 had spread to all 50 US states, with 7,038 cases and 97 deaths.1 The trajectory of cases mirrors that of Italy, where doctors are forced to consider who is more deserving of a ventilator.2 In response, social distancing measures are being promoted across the US in the hopes of slowing the growth in new cases, i.e. "flattening the curve." This could maintain the demand for acute care within the healthcare system's capacity to treat.3 Travel has been curtailed, conferences and concerts cancelled, and schools and universities have moved students off campus and classes online. Medical schools are following suit, with added motivators. In canceling classes and rotations, medical schools hope to: promote social distancing, limit the risk of students contracting the virus, limit the number of healthcare workers who might spread the virus to unaffected patients, minimize the teaching burden on frontline providers, and preserve personal protective equipment (PPE) for essential personnel. These are logical reasons for removing students from hospitals. But, despite our best efforts, there may come a point in the US when, as is set to happen in Italy, medical demand outpaces medical capacity.2 If the same happens here, is there a plan in place for incorporating senior medical students into emergency relief efforts?


title: Public Transport Operations After Lockdown: How to Make It Happen?

text: Lockdown in cities across the globe has imposed severe travel restrictions to limit the spread of Coronavirus disease. The travel behavior and operations will not be the same as before due to requirements such as physical (social) distancing. This study analyzes the resulting shortage in supply of public transport (buses) that will likely widen the existing gap between demand and supply. In this work, system optimization models are developed to efficiently reallocate the bus fleet to routes for different levels of physical distancing gaps and travel demand. The proposed models are applied to a real-life network of 34 bus routes of Delhi, considering three types of scenarios: current, practical, and ideal. In the practical scenarios, the additional, idling bus fleets can be allocated to the routes efficiently while maintaining physical distancing. The results show that the Business-as-Usual (BAU) scenario involving the current allocation approach will make it impossible to use public buses even if the bare minimum physical distancing has to be maintained. Further, the models proposed in the study significantly improve the key performance indicators for all scenarios.


Trombosis y covid-19: atención primaria clave en el abordaje interdisciplinar


title: The psycho-social effects of COVID-19 on Italian adolescents’ attitudes and behaviors

text: BACKGROUND: COVID-19 is an emerging issue that has significant consequences on psycho-social well-being. METHODS: In this regard, a survey was conducted on a large group of adolescents in Italy. The survey investigated four items: concerns and fears, information on the pandemic, provisions of public authorities (e.g., lockdown), and impact on everyday life. RESULTS: Adolescents actively participated in the survey. COVID-19 affected emotions and lifestyle. COVID-19 influenced relationships with peers and parents. There were regional differences. CONCLUSIONS: The current research highlighted the remarkable, healthy, and certainly unexpected, emotional balance of the new generations in the face of a sudden, unpredictable phenomenon capable of jeopardizing life itself. While understanding the gravity of the phenomenon and willingly adapting to all the necessary precautions, the adolescents still seemed to express an excellent ability to manage situations of insecurity and to deal with unfavorable and adverse conditions by adapting to the new routine and finding alternative and innovative means of meeting their social and psychological needs.


Enhancement of SARS-CoV Infection by Proteases


title: The psychosocial effects of being quarantined following exposure to COVID-19: A qualitative study of Lebanese health care workers

text: BACKGROUND: Since the outbreak of the novel Coronavirus (COVID-19), health care professionals in Lebanon have been diligently serving as the frontline of defense. In the light of challenging economic and political circumstances, putting their community wellbeing as a priority, and abiding by quarantine and strict infection control measures, health care professionals risk both their physical and mental wellbeing. OBJECTIVE: The aim of this study is to explore the psychosocial effects of being quarantined following exposure to COVID-19 among Lebanese health care professionals. METHOD: An exploratory qualitative research design was employed, where semi-structured interviews were carried out involving a sample of 13 Lebanese health care providers working at various COVID-19 units. RESULTS: The qualitative analysis has revealed four themes namely ‘Fears of contracting and spreading the virus’, ‘Conflict between professional duty and family obligation’, ‘Stigma of being infected’, and ‘Inadequate or inaccurate information’. CONCLUSION: COVID-19 quarantine has been posing intense psychological challenges among Lebanese health care workers which are worsened at times by the economic instability; thus, health care policymakers are urged to take proper action nationwide to alleviate longlisting implications and support the health care providers in fulfilling their mission.


title: Isolation, purification and immunobiological activity of a new water-soluble bee pollen polysaccharide from Crataegus pinnatifida Bge.

text: Abstract A novel water-soluble polysaccharide was obtained from bee pollen of Crataegus pinnatifida Bge. Two fractions of this polysaccharide, CPP-1 and CPP-2, were first extracted by hot-water and purified. The average molecular weight of CPP-1 and CPP-2 were approximately 3.7×105 Da and 7.8×104 Da, and their chemical structures were studied by gas chromatography (GC), Fourier transform-infrared (FT-IR) spectroscopy, methylation analysis. We evaluated the effects of CPP-1 and CPP-2 on the basis of phagocytosis of macrophage assay, natural killer cells cytotoxicity assay and spleen lymphocyte proliferation assay. The results showed CPP-1 and CPP-2 significantly induced phagocytic rates and phagocytic indexes by peritoneal macrophages. Moreover, these two fractions caused a significant stimulation of rat spleen cell proliferation. At 50μg/mL, CPP-2 activated NK cells more significantly than CPP-1. These findings suggest that they should be explored as a novel potential immunostimulants.


title: Convalescent plasma transfusion for the treatment of COVID‐19: Systematic review

text: The recent emergence of coronavirus disease 2019 (COVID‐19) pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID‐19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID‐19. PubMed, EMBASE, and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria. We included five studies reporting CPT to COVID‐19 patients. The main findings from available data are as follows: (a) Convalescent plasma may reduce mortality in critically ill patients, (b) Increase in neutralizing antibody titers and disappearance of SARS‐CoV‐2 RNA was observed in almost all the patients after CPT therapy, and (c) Beneficial effect on clinical symptoms after administration of convalescent plasma. Based on the limited scientific data, CPT therapy in COVID‐19 patients appears safe, clinically effective, and reduces mortality. Well‐designed large multicenter clinical trial studies should be conducted urgently to establish the efficacy of CPT to COVID‐19 patients.


Coronavirus Pandemic Hits Chinese Coatings Market


title: COVID-19 Suspection: A case report regarding a male emergency medical service pilot with newly diagnosed sarcoidosis

text: Abstract A 38-yr-old Emergency Medical Service Bell 214 male pilot with dry cough, fever, anorexia, fatigue and sweating for the past 3d, oral temperature 38°C, blood pressure 105/65 mm Hg, heart rate 94, respiratory rate 21, and pulse oximetry 93% on room air was suspicious for COVID-19. Surprisingly, RT-PCR was negative but bilateral hilar adenopathy was reported in his chest radiography as new challenge. Pathologic report of adenopathy biopsy was noncaseating sarcoidal type granulomas. Serologic tests shown serum ACE level of 58 nmol/mL/min. Bronchoalveolar lavage had CD4 to CD8 ratio of 3.68. All findings provide accurate sarcoidosis diagnosis and HRCT scan revealed Stage I pulmonary involvement. Due to pulmonary involvement, clinical manifestations, use of inhaled fluticazone, need more longer and accurate follow up and protect against COVID-19, he has been temporarily suspended until the final assignment.


title: Preparing for Pandemic Vaccination: An International Policy Agenda for Vaccine Development

text: The international use of influenza vaccine is growing, especially in developing countries. Since 1997, avian H5N1 influenza in Southeast Asia has caused several human infections and high mortality. Experts warn that the next influenza pandemic is imminent and could be severe. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. If the vaccine supply is to be sufficient to meet global demand, issues related to the intellectual property rights for the reverse genetics technology essential for vaccine production must be resolved. In addition, candidate “pandemic-like” vaccines must be developed and tested in clinical trials to determine the most antigen sparing formulation and the best vaccination schedule. These studies must involve all vaccine companies and will require international coordination and public funding. Whether this international policy agenda for pandemic vaccine development will succeed is uncertain, but it will provide a good indication of whether “good governance” for global public health can be achieved.


Radiology Residency Program Management in the COVID Era – Strategy and Reality


title: Molar absorptivity and A(1cm)(1%) values for proteins at selected wavelengths of the ultraviolet and visible regions—XVIII

text: A table of molar absorptivity and A(1cm)(1%) values for more than 180 proteins is given. The conditions used to obtain these values and references to the original literature are also'given.


title: The problems with contact-tracing apps

text: As countries look to ease restrictions and manage second waves of cases, apps are appealing but fraught with issues, reports Adam Vaughan


title: Nasopharyngeal bacterial load as a marker for rapid and easy diagnosis of invasive pneumococcal disease in children from Mozambique

text: BACKGROUND: Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. METHODS: Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. RESULTS: Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log(10) copies/mL in cases vs. 5.8 log(10) copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log(10) copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). CONCLUSION: Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children.


title: Vaccines for the Elderly: The Quest for the Ideal Animal Model

text: Summary A decline in protective immune responses following vaccination is one of the main features of immunosenescence. Improved vaccine candidates for elderly adults are thus urgently needed. For scientific and regulatory requirements, such new vaccines must first be evaluated at the preclinical level, and there is a continuing quest for the ideal animal model with which to perform such studies. The main advantages and limitations of murine models, those most commonly used for human vaccine research, and of large animal models are reviewed and discussed.


title: A Multicenter Consortium to Define the Epidemiology and Outcomes of Inpatient Respiratory Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

text: BACKGROUND: Respiratory virus infections (RVIs) pose a threat to children undergoing hematopoietic stem cell transplantation (HSCT). In this era of sensitive molecular diagnostics, the incidence and outcome of HSCT recipients who are hospitalized with RVI (H-RVI) are not well described. METHODS: A retrospective observational cohort of pediatric HSCT recipients (between January 2010 and June 2013) was assembled from 9 US pediatric transplant centers. Their medical charts were reviewed for H-RVI events within 1 year after their transplant. An H-RVI diagnosis required respiratory signs or symptoms plus viral detection (human rhinovirus/enterovirus, human metapneumovirus, influenza, parainfluenza, coronaviruses, and/or respiratory syncytial virus). The incidence of H-RVI was calculated, and the association of baseline HSCT factors with subsequent pulmonary complications and death was assessed. RESULTS: Among 1560 HSCT recipients, 259 (16.6%) acquired at least 1 H-RVI within 1 year after their transplant. The median age of the patients with an H-RVI was lower than that of patients without an H-RVI (4.8 vs 7.1 years; P < .001). Among the patients with a first H-RVI, 48% required some respiratory support, and 14% suffered significant pulmonary sequelae. The all-cause and attributable case-fatality rates within 3 months of H-RVI onset were 11% and 5.4%, respectively. Multivariate logistic regression revealed that H-RVI onset within 60 days of HSCT, steroid use in the 7 days before H-RVI onset, and the need for respiratory support at H-RVI onset were associated with subsequent morbidity or death. CONCLUSION: Results of this multicenter cohort study suggest that H-RVIs are relatively common in pediatric HSCT recipients and contribute to significant morbidity and death. These data should help inform interventional studies specific to each viral pathogen.


title: Rapid and efficient detection methods of pathogenic swine enteric coronaviruses

text: ABSTRACT: Porcine enteric coronaviruses (CoVs) cause highly contagious enteric diarrhea in suckling piglets. These COV infections are characterized by clinical signs of vomiting, watery diarrhea, dehydration, and high morbidity and mortality, resulting in significant economic losses and tremendous threats to the pig farming industry worldwide. Because the clinical manifestations of pigs infected by different CoVs are similar, it is difficult to differentiate between the specific pathogens. Effective high-throughput detection methods are powerful tools used in the prevention and control of diseases. The immune system of piglets is not well developed, so serological methods to detect antibodies against these viruses are not suitable for rapid and early detection. This paper reviews various PCR-based methods used for the rapid and efficient detection of these pathogenic CoVs in swine intestines. KEY POINTS: 1. Swine enteric coronaviruses (CoVs) emerged and reemerged in past years. 2. Enteric CoVs infect pigs at all ages with high mortality rate in suckling pigs. 3. Rapid and efficient detection methods are needed and critical for diagnosis.


title: Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multi-céntrico

text: RESUMEN Antecedentes: No se ha reportado plenamente la evolución clínica de los pacientes críticos de COVID-19 durante su ingreso en la unidad de cuidados intensivos (UCI), incluyendo las complicaciones médicas e infecciosas y terapias de soporte, así como su asociación con la mortalidad en ICU. Objetivo: El objetivo de este estudio es describir las características clínicas y la evolución de los pacientes ingresados en UCI por COVID-19, y determinar los factores de riesgo de la mortalidad en UCI de dichos pacientes. Métodos: Estudio prospectivo, multi-céntrico y de cohorte, que incluyó a los pacientes críticos de COVID-19 ingresados en 30 UCIs de España y Andorra. Se incluyó a los pacientes consecutivos de 12 de Marzo a 26 de Mayo de 2020 si habían fallecido o habían recibido el alta de la UCI durante el periodo de estudio. Se reportaron los datos demográficos, síntomas, signos vitales, marcadores de laboratorio, terapias de soporte, terapias farmacológicas, y complicaciones médicas e infecciosas, realizándose una comparación entre los pacientes fallecidos y los pacientes dados de alta. Resultados: Se incluyó a un total de 663 pacientes. La mortalidad general en UCI fue del 31% (203 pacientes). Al ingreso en UCI los no supervivientes eran más hipoxémicos [SpO2 sin mascarilla de no reinhalación, de 90 (RIC 83 - 93) vs 91 (RIC 87 - 94); p<0,001] y con mayor puntuación en la escala SOFA - Evaluación de daño orgánico secuencial - [SOFA, 7 (RIC 5 - 9) vs 4 (RIC 3 - 7); p<0,001]. Las complicaciones fueron más frecuentes en los no supervivientes: síndrome de distrés respiratorio agudo (SDRA) (95% vs 89%; p=0,009), insuficiencia renal aguda (IRA) (58% vs 24%; p<10-16), shock (42% vs 14%; p<10-13), y arritmias (24% vs 11%; p<10-4). Las súper-infecciones respiratorias, infecciones del torrente sanguíneo y los shock sépticos fueron más frecuentes en los no supervivientes (33% vs 25%; p=0,03, 33% vs 23%; p=0,01 y 15% vs 3%, p=10-7), respectivamente. El modelo de regresión multivariable reflejó que la edad estaba asociada a la mortalidad, y que cada año incrementaba el riesgo de muerte en un 1% (95%IC: 1 - 10, p=0,014). Cada incremento de 5 puntos en la escala APACHE II predijo de manera independiente la mortalidad [OR: 1,508 (1,081, 2,104), p= 0,015]. Los pacientes con IRA [OR: 2,468 (1,628, 3,741), p<10-4)], paro cardiaco [OR: 11,099 (3,389, 36,353), p= 0,0001], y shock séptico [OR: 3,224 (1,486, 6,994), p= 0,002] tuvieron un riesgo de muerte incrementado. Conclusiones: Los pacientes mayores de COVID-19 con puntuaciones APACHE II más altas al ingreso, que desarrollaron IRA en grados II o III y/o shock séptico durante la estancia en UCI tuvieron un riesgo de muerte incrementado. La mortalidad en UCI fue del 31%. ABSTRACT Background: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. Objective: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. Methods: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. Results: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs 91 (IQR 87 to 94); p<0.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs 4 (IQR 3 to 7); p<0.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs 89%; p=0.009), acute kidney injury (AKI) (58% vs 24%; p<10-16), shock (42% vs 14%; p<10-13), and arrhythmias (24% vs 11%; p<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs 25%; p=0.03, 33% vs 23%; p=0.01 and 15% vs 3%, p=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, p=0.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), p= 0.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), p<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), p= 0.0001], and septic shock [OR: 3.224 (1.486, 6.994), p= 0.002] had an increased risk-of-death. Conclusions: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades II or III and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.


title: Humanity tested

text: The world needs mass at-home serological testing for antibodies elicited by SARS-CoV-2, and rapid and frequent point-of-care testing for the presence of the virus’ RNA in selected populations.


title: The relationship between liver-kidney impairment and viral load after nephropathogenic infectious bronchitis virus infection in embryonic chickens

text: Abstract To examine the relationship of impairments of the liver and kidney with viral load after nephropathogenic infectious bronchitis virus (NIBV) infection in embryonic chickens, 120 specific-pathogen-free Leghorn embryonated chicken eggs were randomly divided into two groups (infected and control), with three replicates per group and 20 eggs in each replicate. The eggs in the infected and control groups were challenged with 0.2 mL of 105.5 ELD50 NIBV and sterile saline solution, respectively. The embryonic chickens’ plasma and liver and kidney tissues were collected at 1, 3, and 5 days post-inoculation (dpi), the liver and kidney functional parameters were quantified, and the tissue viral loads were determined with real-time PCR. The results showed that plasma potassium, sodium, chlorine, magnesium, calcium, and phosphorus levels were increased. The infected group exhibited significantly higher plasma uric acid, blood urea nitrogen, and creatinine levels than the control group at 3 dpi. The plasma concentrations of aspartate aminotransferase and alanine aminotransferase were significantly increased in the infected group. The total protein, albumin, and globulin levels in the infected group were significantly lower than those in the control group. The liver-kidney viral load in the infected group peaked at 3 dpi, at which time the kidney viral load was significantly higher than that of the liver. Our results indicated that NIBV infection caused liver and kidney damage in the embryonic chickens, and the results also demonstrated that the liver and kidney damage was strongly related to the tissue viral load following NIBV infection in embryonic chickens.


title: A review on HCV inhibitors: Significance of non-structural polyproteins

text: Hepatitis C virus (HCV) mortality and morbidity is a world health misery with an approximate 130–150 million chronically HCV tainted and suffering individuals and it initiate critical liver malfunction like cirrhosis, hepatocellular carcinoma or liver HCV cancer. HCV NS5B protein one of the best studied therapeutic target for the identification of new drug candidates to be added to the combination or multiple combination medication recently approved. During the past few years, NS5B has thus been an important object of attractive medicinal chemistry endeavors, which induced to the surfacing of betrothal preclinical drug molecules. In this scenario, the current review set limit to discuss research published on NS5B and few other therapeutic functional inhibitors concentrating on hit investigation, hit to lead optimization, ADME parameters evaluation, and the SAR data which was out for each compound type and similarity taken into consideration. The discussion outlined in this specific review will surly helpful and vital tool for those medicinal chemists investigators working with HCV research programs mainly pointing on NS5B and set broad spectrum identification of creative anti HCV compounds. This mini review also tells each and every individual compound ability related how much they are active against NS5B and few other targets.


title: Spike gene deletion quasispecies in serum of patient with acute MERS‐CoV infection

text: The spike glycoprotein of the Middle East respiratory coronavirus (MERS‐CoV) facilitates receptor binding and cell entry. During investigation of a multi‐facility outbreak of MERS‐CoV in Taif, Saudi Arabia, we identified a mixed population of wild‐type and variant sequences with a large 530 nucleotide deletion in the spike gene from the serum of one patient. The out of frame deletion predicted loss of most of the S2 subunit of the spike protein leaving the S1 subunit with an intact receptor binding domain. This finding documents human infection with a novel genetic variant of MERS‐CoV present as a quasispecies. J. Med. Virol. 89:542–545, 2017. © 2016 Wiley Periodicals, Inc.


title: Assessment of samples pooling for SARS-CoV-2 molecular testing for screening of asymptomatic persons in Tunisia

text: Abstract The aim of this study is to test a pooling approach for the RT-PCR test to detect low viral loads of SARS-CoV-2. We found that a single positive specimen can still be detected in pools of up to 10. Each laboratory should conduct its own evaluation and validation of pooling protocols according to its specific context.


title: An update on antiviral antibody-based biopharmaceuticals

text: Due to the vastness of the science virology, it is no longer an offshoot solely of the microbiology. Viruses have become as the causative agents of major epidemics throughout history. Many therapeutic strategies have been used for these microorganisms, and in this way the recognizing of potential targets of viruses is of particular importance for success. For decades, antibodies and antibody fragments have occupied a significant body of the treatment approaches against infectious diseases. Because of their high affinity, they can be designed and engineered against a variety of purposes, mainly since antibody fragments such as scFv, nanobody, diabody, and bispecific antibody have emerged owing to their small size and interesting properties. In this review, we have discussed the antibody discovery and molecular and biological design of antibody fragments as inspiring therapeutic and diagnostic agents against viral targets.


Confinée mais mobilisée, l’Académie nationale de médecine au temps de la Covid-19


title: Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

text: Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1–7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1–7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.


title: Mobilization practices in critically ill children: a European point prevalence study (EU PARK-PICU)

text: BACKGROUND: Early mobilization of adults receiving intensive care improves health outcomes, yet little is known about mobilization practices in paediatric intensive care units (PICUs). We aimed to determine the prevalence of and factors associated with physical rehabilitation in PICUs across Europe. METHODS: A 2-day, cross-sectional, multicentre point prevalence study was conducted in May and November 2018. The primary outcome was the prevalence of physical therapy (PT)- or occupational therapy (OT)-provided mobility. Clinical data and data on patient mobility, potential mobility safety events, and mobilization barriers were prospectively collected in patients admitted for ≥72 h. RESULTS: Data of 456 children admitted to one of 38 participating PICUs from 15 European countries were collected (456 patient days); 70% were under 3 years of age. The point prevalence of PT- and/or OT-provided mobility activities was 39% (179/456) (95% CI 34.7–43.9%) during the patient days, with significant differences between European regions. Nurses were involved in 72% (924/1283) of the mobility events; in the remaining 28%, PT/OT, physicians, family members, or other professionals were involved. Of the factors studied, family presence was most strongly positively associated with out-of-bed mobilization (aOR 7.83, 95% CI 3.09–19.79). Invasive mechanical ventilation with an endotracheal tube was negatively associated with out-of-bed mobility (aOR 0.28, 95% CI 0.12–0.68). Patients were completely immobile on 25% (115/456) of patient days. Barriers to mobilization were reported on 38% of patient days. The most common reported patient-related barriers were cardiovascular instability (n = 47, 10%), oversedation (n = 39, 9%), and medical contraindication (n = 37, 8%). Potential safety events occurred in 6% of all documented mobilization events. CONCLUSION: Therapists are infrequently consulted for mobilization of critically ill children in European PICUs. This study highlights the need for a systematic and interdisciplinary mobilization approach for critically ill children. GRAPHICAL ABSTRACT: [Image: see text]


title: Chapter 23 Lung, Pleura, and Mediastinum

text: Abstract The lung is constantly exposed to a large volume of inhaled air that may contain toxicant xenobiotics. With the possibility of exposure to a variety of respiratory toxicants from airborne pollutants in our environment during the course of daily activities, in occupational settings, the use of aerosol sprays for household products, and the development of inhalant bronchial therapies, pulmonary toxicology has become an important subspecialty of toxicology. The lung is susceptible to injury following hematogenous exposure to toxicants. Susceptibility to injury and the type of response following exposure to air- or blood-borne toxicants is largely dependent on the physiochemical characteristics and concentration of the toxicant, duration of exposure, site/tissue specific sensitivity, and the integrity of the defense mechanisms of the lung. In this chapter, nonneoplastic and neoplastic spontaneous lesions and those that develop in the lungs of rats following exposure to toxicants by various routes, but primarily by inhalation, are discussed in detail which provides insight into our understanding of how human lungs respond to toxic chemicals. In addition, the gross and microscopic anatomy of the rat lung is also discussed some detail. Although inhalation is the primary route of exposure in experimental studies, in the past, many studies used intratracheal instillation or direct injection of known carcinogens into the lung. These experiments often resulted in the development of squamous cell carcinomas even though they are very rare as a naturally occurring neoplasm. Instillation of chemicals or particles into the trachea or pleura or direct injection into the lung results in lesions or responses that may not be as relevant to understanding the mechanism of pulmonary carcinogenesis as inhalation of materials under more normal conditions. There remain, however, many areas where our understanding of the response of the lung to toxic chemicals is incomplete.


title: Decent Work, ILO’s Response to the Globalization of Working Life: Basic Concepts and Global Implementation with Special Reference to Occupational Health

text: Twenty years ago, the International Labour Organization (ILO) launched a new strategy, the Decent Work Agenda, to ensure human-oriented development in the globalization of working life and to provide an effective response to the challenges of globalization. We searched for and analysed the origin of the Decent Work concept and identified the key principles in ILO policy documents, survey reports, and relevant United Nations’ (UN) documents. We also analysed the implementation of the Decent Work Country Programmes (DWCPs) and examined the available external evaluation reports. Finally, we examined the objectives of the ILO Decent Work Agenda and the Decent Work targets in the UN 2030 Agenda for Sustainable Development in view of occupational health. In two thirds of the ILO’s Member States, the Decent Work Agenda has been successfully introduced and so far fully or partly implemented in their DWCPs. The sustainability of the Decent Work approach was ensured through the UN 2030 Agenda, the ILO Global Commission Report on the Future of Work, and the ILO Centenary Declaration. However, objectives in line with the ILO Convention No. 161 on Occupational Health Services were not found in the DWCPs. Although successful in numerous aspects in terms of the achievement of the Decent Work objectives and the UN Sustainable Development Goals (SDGs), the Decent Work Agenda and the Decent Work Country Programmes need further development and inclusion of the necessary strategies, objectives, and actions for occupational health services, particularly in view of the high burden of work-related diseases and, for example, the present global pandemic. In many countries, national capabilities for participation and implementation of Decent Work Country Programmes need strengthening.


title: Hybrid Coordination for Coping with the Medical Surge from the COVID‐19 Pandemic: Paired‐Assistance Programs in China

text: The COVID‐19 pandemic poses unprecedented challenges to public healthcare systems and demands intergovernmental coordination to cope with the resulting medical surge. This article analyzes the operation of Paired Assistance Programs (PAPs) in China, offering a timely comparative case for researchers and practitioners to examine when reflecting on the classic debate over the hierarchical versus network approaches to coordination in emergency management. PAPs highlight the importance of network management and necessity of institutionalizing mechanisms of governance to facilitate coordination within multilevel response systems. This article is protected by copyright. All rights reserved.