title: Pattern of early human-to-human transmission of Wuhan 2019-nCoV

text: On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4—3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.


title: Applying high-performance computing in drug discovery and molecular simulation

text: In recent decades, high-performance computing (HPC) technologies and supercomputers in China have significantly advanced, resulting in remarkable achievements. Computational drug discovery and design, which is based on HPC and combines pharmaceutical chemistry and computational biology, has become a critical approach in drug research and development and is financially supported by the Chinese government. This approach has yielded a series of new algorithms in drug design, as well as new software and databases. This review mainly focuses on the application of HPC to the fields of drug discovery and molecular simulation at the Chinese Academy of Sciences, including virtual drug screening, molecular dynamics simulation, and protein folding. In addition, the potential future application of HPC in precision medicine is briefly discussed.


Walkie talkies to aid health care workers’ compliance with personal protective equipment in the fight against COVID-19


title: Chapter 10 Bioaugmentation for the treatment of waterborne pathogen contamination water

text: Abstract Bioaugmentation is an eco-friendly and economically viable approach for enhanced degradation of pollutants and pathogens by addition of pregrown microbe or microbial cocultures in the medium. Microorganisms from different ecological conditions and engineered microbes capable to produce versatile enzymes and bioproducts are added to native microbial population for in situ treatment of wastewater. Bacterial pathogen borne in wastewater is an important concern for public health because they are not only associated with environmental damage, morbidity, and mortality but also cause economic loss connected with physical and chemical methods in wastewater treatment. Bacteriophages are natural killer of bacteria; they can be used as an alternative, cost-effective, biological method for waterborne bacterial pathogen control. Legionella pneumophila is the most tracked waterborne pathogen requiring specific treatment conditions because despite of biocides use, they are able to persist in water supplies with the help of multispecies biofilms and phagocytic protists. This type of pathogens can be biologically controlled through native complex communities fight for nutrients by means of antagonistic molecules as war weapons. Bioinoculation of heterotrophic bacterial strains in different wastewater treatment systems improves the process of pathogenic bacteria removal. The antagonist substances produced by the inoculated strains are responsible for bacterial pathogen inactivation.


title: APA calls for telecommunications use to prevent virus spread

text: The American Psychological Association (APA) on March 24 called on states and insurers to move quickly to allow people to connect with their mental health providers remotely using telehealth as the need for mental health services rises during the COVID‐19 pandemic. “We are asking state policymakers to temporarily suspend state licensing requirements for telepsychological services, which would allow patients greater access to their providers and ensure continuity of care during this crisis,” Arthur C. Evans Jr., Ph.D., APA's CEO, said in a statement. “The federal government has just identified psychologists as critical, essential workers in the U.S. response to COVID‐19. But this does not mean that psychologists and psychology trainees must do work in person,” he said. “Essential psychological services can, and in many cases, should be delivered through telehealth. It is critically important that psychologists are able to meet the needs of their patients and communities during this difficult time, without further increasing the risk of contagion.”


title: Does bronchoscopy help the diagnosis in Covid-19 infection?

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic. This virus is predominantly spread through large droplets. The clinical features of COVID-19 are varied, ranging from asymptomatic to acute respiratory distress syndrome and multi-organ dysfunction [1].


title: Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity

text: Both viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-γ resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.


title: Cytomegalovirus infection in a patient with atypical Kawasaki disease

text: Kawasaki disease (KD) is an acute, febrile, and multisystem vasculitis of early childhood with a striking predilection for the coronary arteries. The most significant complication is coronary artery abnormalities, including coronary aneurysms. The etiology of KD remains unknown. Many infectious agents including viruses have been postulated as possible causes of KD. But standard microbiologic techniques, molecular methods and serologic investigations have failed to identify an etiologic agent. We described a patient with atypical KD during cytomegalovirus infection.


title: The Battle Against COVID-19 in Jordan: An Early Overview of the Jordanian Experience

text: Since the initial spark of the COVID-19 outbreak in December 2019, which was later declared by the World Health Organization (WHO) to be a global pandemic, all affected countries are implementing various preventive and control measures to mitigate the spread of the disease. The newly emerging virus brings with it uncertainty—not only regarding its behavior and transmission dynamics but also regarding the current lack of approved antiviral therapy or vaccines—and this represents a major challenge for decision makers at various levels and sectors. This article aims to provide an early overview of the COVID-19 battle within the Jordanian context, including general reflections and conclusions on the value of collaborative efforts in crises management.


title: The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study

text: Abstract Objective To study the effect of corticosteroids in the treatment of severe acute respiratory syndrome (SARS). Methods A retrospective cohort of 78 consecutive adult SARS patients admitted to a regional hospital in Hong Kong between March and May 2003 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, comorbidities, peak lactate dehydrogenase (LDH) levels and clinical outcomes. Established adverse prognostic factors including old age, comorbidities and high LDH levels were used as covariates in multiple logistic regressions to adjust for their confounding effect on adverse outcomes. Results Among 78 patients, 66 patients (84.6%) received corticosteroid. The LDH level was similar in both groups. The corticosteroid group had more adverse outcomes (37.9% vs. 16.7%) despite younger age and less comorbidity. In multivariate analysis, corticosteroid treatment was associated with a 20.7-fold increase in risk of either ICU admission or mortality, independent of age and disease severity. Conclusion Despite more favourable baseline characteristics and similar peak LDH levels, SARS patients given corticosteroid had more adverse outcomes.


title: Molecular detection and point-of-care testing in Ebola virus disease and other threats: a new global public health framework to stop outbreaks

text: Ultrahigh sensitivity and specificity assays that detect Ebola virus disease or other highly contagious and deadly diseases quickly and successfully upstream in Spatial Care Paths™ can stop outbreaks from escalating into devastating epidemics ravaging communities locally and countries globally. Even had the WHO and CDC responded more quickly and not misjudged the dissemination of Ebola in West Africa and other world regions, mobile rapid diagnostics were, and still are, not readily available for immediate and definitive diagnosis, a stunning strategic flaw that needs correcting worldwide. This article strategizes point-of-care testing for diagnosis, triage, monitoring, recovery and stopping outbreaks in the USA and other countries; reviews Ebola molecular diagnostics, summarizes USA FDA emergency use authorizations and documents why they should not be stop-gaps; and reduces community risk from internal and external infectious disease threats by enabling public health at points of need.


title: Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza

text: IMPORTANCE: During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. OBJECTIVE: To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. EXPOSURES: Prescription fill of an NSAID within 60 days before admission. MAIN OUTCOMES AND MEASURES: Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. RESULTS: A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, –0.7%; 95% CI, –3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, –0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, –2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). CONCLUSIONS AND RELEVANCE: In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.


title: SARS-CoV-2 Evolutionary Adaptation toward Host Entry and Recognition of Receptor O-Acetyl Sialylation in Virus–Host Interaction

text: The recently emerged SARS-CoV-2 is the cause of the global health crisis of the coronavirus disease 2019 (COVID-19) pandemic. No evidence is yet available for CoV infection into hosts upon zoonotic disease outbreak, although the CoV epidemy resembles influenza viruses, which use sialic acid (SA). Currently, information on SARS-CoV-2 and its receptors is limited. O-acetylated SAs interact with the lectin-like spike glycoprotein of SARS CoV-2 for the initial attachment of viruses to enter into the host cells. SARS-CoV-2 hemagglutinin-esterase (HE) acts as the classical glycan-binding lectin and receptor-degrading enzyme. Most β-CoVs recognize 9-O-acetyl-SAs but switched to recognizing the 4-O-acetyl-SA form during evolution of CoVs. Type I HE is specific for the 9-O-Ac-SAs and type II HE is specific for 4-O-Ac-SAs. The SA-binding shift proceeds through quasi-synchronous adaptations of the SA-recognition sites of the lectin and esterase domains. The molecular switching of HE acquisition of 4-O-acetyl binding from 9-O-acetyl SA binding is caused by protein–carbohydrate interaction (PCI) or lectin–carbohydrate interaction (LCI). The HE gene was transmitted to a β-CoV lineage A progenitor by horizontal gene transfer from a 9-O-Ac-SA–specific HEF, as in influenza virus C/D. HE acquisition, and expansion takes place by cross-species transmission over HE evolution. This reflects viral evolutionary adaptation to host SA-containing glycans. Therefore, CoV HE receptor switching precedes virus evolution driven by the SA-glycan diversity of the hosts. The PCI or LCI stereochemistry potentiates the SA–ligand switch by a simple conformational shift of the lectin and esterase domains. Therefore, examination of new emerging viruses can lead to better understanding of virus evolution toward transitional host tropism. A clear example of HE gene transfer is found in the BCoV HE, which prefers 7,9-di-O-Ac-SAs, which is also known to be a target of the bovine torovirus HE. A more exciting case of such a switching event occurs in the murine CoVs, with the example of the β-CoV lineage A type binding with two different subtypes of the typical 9-O-Ac-SA (type I) and the exclusive 4-O-Ac-SA (type II) attachment factors. The protein structure data for type II HE also imply the virus switching to binding 4-O acetyl SA from 9-O acetyl SA. Principles of the protein–glycan interaction and PCI stereochemistry potentiate the SA–ligand switch via simple conformational shifts of the lectin and esterase domains. Thus, our understanding of natural adaptation can be specified to how carbohydrate/glycan-recognizing proteins/molecules contribute to virus evolution toward host tropism. Under the current circumstances where reliable antiviral therapeutics or vaccination tools are lacking, several trials are underway to examine viral agents. As expected, structural and non-structural proteins of SARS-CoV-2 are currently being targeted for viral therapeutic designation and development. However, the modern global society needs SARS-CoV-2 preventive and therapeutic drugs for infected patients. In this review, the structure and sialobiology of SARS-CoV-2 are discussed in order to encourage and activate public research on glycan-specific interaction-based drug creation in the near future.


title: Resistance to cyfluthrin and tetrachlorvinphos in the lesser mealworm, Alphitobius diaperinus, collected from the eastern United States

text: The lesser mealworm, Alphitobius diaperinus (Panzer), is an important pest in poultry facilities. The toxicity of cyfluthrin and tetrachlorvinphos to five strains of the lesser mealworm was compared with the toxicity to a susceptible laboratory strain. Bioassays were carried out with both larvae and adults. For the susceptible strain, cyfluthrin and tetrachlorvinphos had similar toxicity to adults, but cyfluthrin was 5 times more toxic to larvae when compared with tetrachlorvinphos. High levels of resistance to tetrachlorvinphos in two beetle strains were detected in both larvae and adults, although these strains were heterogeneous and still contained susceptible individuals. Resistance to cyfluthrin ranged from 1.7‐ to 9.5‐fold for adults and from 0.5‐ to 29‐fold for larvae at the LC(95). Overall, the patterns of resistance did not mirror the insecticide use patterns reported at these facilities. The implications of these results to management of the lesser mealworms are discussed. Copyright © 2006 Society of Chemical Industry


title: Inhibition of the assembly of Newcastle disease virus by monensin

text: Abstract Monensin inhibits the intracellular transport of the glycoproteins of Newcastle disease virus between cis and trans Golgi stacks of infected BHK cells, as evidenced by its effect upon their post-translational modifications such as fatty acid acylation, glycosylation and proteolytic cleavage. Thus the drug has markedly altered the subcellular distribution of the glycoproteins so that they accumulate in the internal smooth membranes but are virtually absent in the plasma membrane. These glycoproteins that accumulated in intracellular membranes have a cytoplasmic domain susceptible to protease digestion and thus are transmembranous. Under such conditions, the behavior of M protein, which plays a crucial role in virus assembly (Y. Nagai et al., 1976, Virology 69, 523–538), has been analyzed. It has been found that the M protein can neither associate with the internal membranes nor bind to the plasma membrane. Thus no virus budding has been observed, either at the plasma membranes or at internal membranes. These results substantiate the view that the interaction between M and glycoproteins is of great importance for virus assembly and suggest further that this interaction is possible only when the glycoproteins have been incorporated into the plasma membrane.


title: Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts

text: BACKGROUND: Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas. METHODS: Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O(2)/5% CO(2)) or normoxic (21% O(2)/5% CO(2)) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein. RESULTS: Hyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α−converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05). CONCLUSION: These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2015.27) contains supplementary material, which is available to authorized users.


Inpatient care for dermatological patients during SARS‐CoV‐2 – a case report from Portugal


title: A picornaviral loop-to-loop replication complex

text: Abstract Picornaviruses replicate their RNA genomes through a highly conserved mechanism that involves an interaction between the principal viral protease (3Cpro) and the 5′-UTR region of the viral genome. The 3Cpro catalytic site is the target of numerous replication inhibitors. This paper describes the first structural model of a complex between a picornaviral 3Cpro and a region of the 5′-UTR, stem-loop D (SLD). Using human rhinovirus as a model system, we have combined NMR contact information, small-angle X-ray scattering (SAXS) data, and previous mutagenesis results to determine the shape, position and relative orientation of the 3Cpro and SLD components. The results clearly identify a 1:1 binding stoichiometry, with pronounced loops from each molecule providing the key binding determinants for the interaction. Binding between SLD and 3Cpro induces structural changes in the proteolytic active site that is positioned on the opposite side of the protease relative to the RNA/protein interface, suggesting that subtle conformational changes affecting catalytic activity are relayed through the protein.


title: Coronavirus and its implications for psychiatry: a rapid review of the early literature

text: BACKGROUND: The novel coronavirus pandemic has changed healthcare rapidly and dramatically. We provide a critical synthesis of the scientific literature on the pandemic’s implications for psychiatric practice. METHODS: A rapid literature review was undertaken to identify scientific literature linking psychiatric outcomes and practice changes due to coronavirus and the disease it causes (COVID-19). A structured quality assessment was used to assess those articles reporting quantitative data. RESULTS: Fifty articles were identified for inclusion, but only 12 contained original data. Eleven of those twelve were rated as poor quality. The literature described psychiatric sequelae of the coronavirus and related public health interventions through cross-sectional surveys among different populations; no studies include diagnostic or functional impairment data. Populations at risk include COVID-19 survivors, healthcare workers, the elderly, and those with pre-existing psychiatric disease. Impacts on psychiatric practice were described, again without data on changes to quality or access of care. CONCLUSIONS: There is a quickly accumulating body of evidence on the psychiatric implications of coronavirus including psychological effects on the general public and at-risk subgroups. Similarly, psychiatric practice has witnessed substantial adaptation to the pandemic. However, these reports are largely anecdotal at this point. Few data characterize these trends, and the early scientific findings are of generally poor quality.


docid: jerovngt

title: La communication sur le SRAS : un outil essentiel de santé publique


title: Nanoscale Particles for Lung Delivery of siRNA

text: Small interfering RNAs (siRNAs) are potent molecules capable of blocking gene expression after entering cell cytoplasm. Despite their strong efficacy, they need to be carried by nanoscale delivery systems that can protect them against degradation in biological fluids, increase their cellular uptake and favor their subcellular distribution. Several studies have highlighted the potential of local pulmonary delivery of siRNAs for the treatment of lung diseases. For this purpose, nanoscale delivery systems were addressed to target passively or actively the target cell. This review discusses the possibilities of approaching lung delivery of nanoscale particles carrying siRNAs.


A WEB-BASED GROUP TREATMENT FOR PATIENTS WITH ALCOHOLIC LIVER DISEASES AT THE TIME OF THE COVID-19 PANDEMIC


title: Structural basis of a public antibody response to SARS-CoV-2

text: Molecular-level understanding of human neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and facilitate drug discovery. We analyzed 294 SARS-CoV-2 antibodies and found that IGHV3–53 is the most frequently used IGHV gene for targeting the receptor binding domain (RBD) of the spike (S) protein. We determined crystal structures of two IGHV3–53 neutralizing antibodies +/− Fab CR3022 ranging from 2.33 to 3.11 Å resolution. The germline-encoded residues of IGHV3–53 dominate binding to the ACE2 binding site epitope with no overlap with the CR3022 epitope. Moreover, IGHV3–53 is used in combination with a very short CDR H3 and different light chains. Overall, IGHV3–53 represents a versatile public VH in neutralizing SARS-CoV-2 antibodies, where their specific germline features and minimal affinity maturation provide important insights for vaccine design and assessing outcomes.


title: Comparative Carcinogenicity in Sprague-Dawley Rats of the Polychlorinated Biphenyl Mixtures Aroclors 1016, 1242, 1254, and 1260

text: A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females > males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 ≈ Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.


title: Cellular immune responses of pigs after primary inoculation with porcine respiratory coronavirus or transmissible gastroenteritis virus and challenge with transmissible gastroenteritis virus

text: Abstract The contribution of cell-mediated immunity to protective immunity against virulent transmissible gastroenteritis virus (TGEV) infection conferred by primary porcine respiratry coronavirus (PRCV) or TGEV exposure was assessed in pigs that were challenged with TGEV 24 days after a primary oronasal inoculation with PRCV or TGEV when 11 days old. PRCV exposure induced partial protection against TGEV challenge in suckling pigs based upon a decreased number of diarrhea cases (42% vs. 90% in age-matched control pigs), limited virus shedding in feces, and increases in virus-neutralizing serum antibody titers; in contrast, all 11-day-old pigs inoculated with TGEV were completely protected after challenge. Weaned pigs were also studied to eliminate any possibility that lactogenic immunity from contact PRCV-exposed sows contributed to protection against TGEV. Once weaned, none of the PRCV-exposed or age-matched control pigs had diarrhea after TGEV challenge; moreover, both groups exhibited less rectal virus shedding than suckling pigs. Vigorous lymphocyte proliferative responses (> 96 000 counts per minute (cpm)) were detected in mononuclear cells prepared from mesenteric (MLN) and bronchial (BLN) lymph nodes of TGEV-primed pigs. Analyses of these responses indicate that virus-specific cell-mediated immune responses correlated with protection against rectal and nasal virus shedding after TGEV challenge. Primary inoculation of 11-day-old pigs with PRCV induced moderate, transient virus-specific lymphocyte proliferation (> 47 000 cpm) in MLN from both suckling and weaned pigs after TGEV challenge. Substantial BLN proliferative responses (> 80 000 cpm) correlated with failure to detect TGEV in nasal secretions from these pigs. Virus-specific lymphocyte proliferation in spleens was delayed in onset and of lower magnitude than that observed in MLN and BLN. Virulent TGEV exposure resulted in increased percentages of T cell subsets, especially in the lamina propria and MLN, mucosaassociated lymphoid tissues in proximity to the primary replication site of TGEV in the small intestine. Our results confirm that PRCV infection primes anti-viral immune responses and, thus, contributes to partial immunity against virulent TGEV challenge.


Autoimmunity to nervous tissue antigens after viral infections


title: Ebola Virus Infection: Overview and Update on Prevention and Treatment

text: In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July 2015, a total of 27,741 EVD cases and 11,284 deaths were reported from all affected countries. Several therapeutic agents and novel vaccines for EVD have been developed and are now undergoing evaluation. Concurrent with active case investigation, contact tracing, surveillance and supportive care to patients and communities, there has been rapid progress in the development of new therapies and vaccines against EVD. Continued focus on strengthening clinical and public health infrastructure will have direct benefits in controlling the spread of EVD and will provide a strong foundation for deployment of new drugs and vaccines to affected countries when they become available. The unprecedented West Africa Ebola outbreak, response measures, and ensuing drug and vaccine development suggest that new tools for Ebola control may be available in the near future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0079-5) contains supplementary material, which is available to authorized users.


title: Coronavirus immunogens

text: Abstract Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIVP) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease. Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems. Coronaviruses are spherical, enveloped viruses, ranging from 80–160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150–200 kDa), the integral membrane glycoprotein (M; 20–30 kDa) and the nucleocapsid phosphoprotein (N; 43–50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60–65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA. Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of αIFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear. Similarly, studies of IBV have suggested that determinants recognized by T cells reside on the N protein and these determinants may be shared among heterologous strains of IBV, resulting in the induction of cross-protection. Thus epitopes on the N protein may be important for induction of cell mediated immunity (CMI). CMI may play an important role in protection of cats against FIPV, since induction of circulating antibodies to the S protein of FIPV contributes to disease pathogenesis by the induction of immune complexes and antibody dependent enhancement of the infectivity of FIPV for macrophages. An increased understanding of antibody and CMI responses following natural CV infections in animals is needed to identify the antigens and epitopes that induce protective immune responses. The expression of CV structural protein genes in various vectors will provide the recombinant proteins needed for future immunogenicity studies in the host species. Furthermore, live rDNA vectors that replicate in the gut and express coronavirus genes may provide a new generation of coronavirus vaccines.


title: Could COVID‐19 have an impact on male fertility?

text: The pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to several hypotheses of functional alteration of different organs. The direct influence of this virus on the male urogenital organs is still to be evaluated. However some hypotheses can already be made, especially in the andrological field, for the biological similarity of the SARS‐CoV and SARS‐CoV2. As well as SARS‐CoV, SARS CoV‐2 uses the ‘Angiotensin Converting Enzyme‐2’ (ACE2) as a receptor to enter human cells. It was found that ACE2, Angiotensin (1‐7) and its MAS receptors are present, over in the lung, also in the testicles, in particular in Leydig and Sertoli cells. A first hypothesis is that the virus could enter the testicle and lead to alterations in testicular functionality. A second hypothesis is that the binding of the virus to the ACE2 receptor, could cause an excess of ACE2 and give rise to a typical inflammatory response. The inflammatory cells could interfere with the function of Leydig and Sertoli cells. Both hypotheses should be evaluated and confirmed, in order to possibly monitor fertility in patients COVID‐19+.


title: Molecular Evolution of Human Coronavirus Genomes

text: Human coronaviruses (HCoVs), including SARS-CoV and MERS-CoV, are zoonotic pathogens that originated in wild animals. HCoVs have large genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ in number and sequence even among closely related CoVs. Thus, in addition to recombination and mutation, HCoV genomes evolve through gene gains and losses. In this review we summarize recent findings on the molecular evolution of HCoV genomes, with special attention to recombination and adaptive events that generated new viral species and contributed to host shifts and to HCoV emergence. Video Abstract


title: Pandemic Bonds

text: Giveaways to the righ or toxic to investors? Or, perhaps, a concept that is the best path to a peaceful, secure, prosperous future.


title: Outbreak of Porcine Epidemic Diarrhea Virus in Portugal, 2015

text: An outbreak of porcine epidemic diarrhea virus (PEDV) in the South of Portugal in January 2015 and the spread of PEDV northwards in the territory are described. Comparative analysis of the amplified sequences showed a very high (99.0%) identity with the PEDV variant most recently reported in the United States and also show complete (100%) identity to the strains recently reported in Germany, supporting the hypothesis that a unique strain is currently circulating in Europe. The origin of this PEDV variant still needs to be elucidated and further studies in the remaining European countries may contribute to the knowledge.


title: La maladie de Parkinson est-elle une maladie à prion ?

text: Résumé L’accumulation d’une protéine spécifique sous forme agrégée est un phénomène commun aux maladies neurodégénératives humaines. Dans la maladie de Parkinson, cette protéine est l’α-synucléine qui est une protéine neuronale de 143 acides aminés. De conformation monomérique en solution, elle possède également une capacité naturelle à s’agréger en structures amyloïdes (dimères, oligomères, fibrilles puis corps ou neurites de Lewy). Elle détient donc les caractéristiques d’une protéine prion (différentes conformations, initiation et dissémination d’un processus transconformationnel). De nombreux arguments expérimentaux in vitro et in vivo sur des animaux transgéniques ou sauvages sont en faveur d’une progression prion-like de la maladie de Parkinson. La diffusion séquentielle et prédictive de l’α-synucléine mise en évidence par Braak et al. et sa corrélation avec les signes non moteurs vont tout à fait dans le sens de cette progression prion-like. Même si le facteur déclenchant à l’origine du mauvais repliement et de l’agrégation de la protéine cible reste inconnu, la maladie de Parkinson est un modèle très pertinent pour l’étude de ces mécanismes et aussi pour tester des traitements spécifiques ciblant les assemblages d’α-synucléine et leur propagation dès la phase pré-motrice de la maladie. Malgré cette progression prion-like, il n’existe actuellement aucun argument indiquant un risque de transmission interhumaine de la maladie de Parkinson. Abstract The accumulation of a specific protein in aggregated form is a common phenomenon in human neurodegenerative diseases. In Parkinson's disease, this protein is α-synuclein which is a neuronal protein of 143 amino acids. With a monomeric conformation in solution, it also has a natural capacity to aggregate into amyloid structures (dimers, oligomers, fibrils and Lewy bodies or neurites). It therefore fulfils the characteristics of a prion protein (different conformations, seeding and spreading). In vitro and in vivo experimental evidence in transgenic and wild animals indicates a prion-like propagation of Parkinson's disease. The sequential and predictive distribution of α-synuclein demonstrated by Braak et al. and its correlation with non-motor signs are consistent with the prion-like progression. Although the triggering factor causing the misfolding and aggregation of the target protein is unknown, Parkinson's disease is a highly relevant model for the study of these mechanisms and also to test specific treatments targeting the assemblies of α-synuclein and propagation from pre-motor phase of the disease. Despite this prion-like progression, there is currently no argument indicating a risk of human transmission of Parkinson's disease.


title: Pathogenesis of COVID-19 from a cell biologic perspective

text: COVID-19 can be understood by the region of the lung that is infected. Mild disease will be confined to the conducting airways and severe disease will involve the gas exchange portion of the lung.


title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach

text: Recently, a novel coronavirus (SARS‐COV‐2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS‐CoV and MERS‐CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS‐COV‐2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex‐(MHC) I and 3 MHC‐II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll‐like receptor‐5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.


title: From Slippery Slopes to Steep Hills: Contrasting Landscapes of Economic Growth and Public Spending for Health

text: Identifying ways to increase public spending on health is critical for the achievement of universal health coverage. While policymakers and donors often look at available options for increasing public spending for health in the medium-term, examining trends and drivers of past growth can help countries elucidate important lessons and to anticipate changes in the future. This note analyzes trends in inflation-adjusted per capita public spending for health vis-à-vis economic growth within and across a sample of 150 countries over the 2000-2017 period. Since 2000, per capita public spending for health across low- and middle-income countries has more than doubled. Less than one-fifth of this increase, however, resulted from a higher priority for health in government budgets. The remainder was largely due to conducive macroeconomic conditions such as economic growth and increases in total public spending. Furthermore, across most countries, a single time trend does not adequately capture the evolution either of economic growth or of per capita public spending on health. Instability in growth rates is large for both indicators, revealing distinct episodic patterns.


title: Short-term exposure to ambient air quality of the most polluted Indian cities due to lockdown amid SARS-CoV-2

text: Air pollution has happened to be one of the mounting alarms to be concerned with in many Indian cities. COVID-19 epidemic endow with a unique opportunity to report the degree of air quality improvement due to the nationwide lockdown in 10 most polluted cities across the country. National Air Quality Index (NAQI) based on continuous monitoring records of seven criteria pollutants (i.e. common air pollutants with known health impacts e.g. PM(10), PM(2.5), CO, NO(2), SO(2), NH(3) and O(3)) for a total of 59 stations across the cities, satellite image derived Aerosol Optical Depth (AOD) and few statistical tools are employed to derive the outcomes. NAQI results convey that 8 cities out of the 10 air quality restored to good to satisfactory category during the lockdown period. Within week+1 of the lockdown period, PM(10) and PM(2.5) concentrations have suppressed below the permissible limit in all cities. CO and NO(2) have reduced to about -30% and -57% respectively during the lockdown period. Diurnal concentrations of PM(10) and PM(2.5) have dropped drastically on the very 4(th) day of lockdown and become consistent with minor hourly vacillation. In April 2020 the AOD amount was reduced to about 36% and 18% in contrast to April 2018 and April 2019 respectively. This add-on reporting of the possible recovery extent in air quality may help to guide alternative policy intervention in form of short term lockdown so as to testify whether this type of unconventional policy decisions may be put forward to attain a green environment.. Because, despite numerous restoration plans, air pollution levels have risen unabated in these cities. However, detailed inventory needs to be focused on identifying the localized pollution hotspots (i.e. source contribution).


title: Sequential nearest-neighbor effects on computed (13)C(α) chemical shifts

text: To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of (13)C(α) chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed (13)C(α) chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical (13)C(α) chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed (13)C(α) chemical shifts, Δ(ca,i), for the individual residues along the sequence. This indicates that the Δ(ca,i) -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.


title: Functional plasticity of antibacterial EndoU toxins

text: Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CT(STECO31) from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CT(STECO31) and other clade III toxins are specific anticodon nucleases that cleave tRNA(Glu) between nucleotides C37 and m(2)A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems.


title: Characteristics of U.S. Nursing Homes with COVID‐19 Cases

text: BACKGROUND: COVID‐19 has been documented in a large share of nursing homes throughout the United States. This has led to high rates of mortality for residents. In order to understand how to prevent and mitigate future outbreaks, it is imperative that we understand which nursing homes are more likely to experience COVID‐19 cases. OBJECTIVE: To examine the characteristics of nursing homes with documented COVID‐19 cases in 30 states reporting individual facilities affected. DESIGN AND SETTING: We constructed a database of nursing homes with verified COVID‐19 cases as of May 11, 2020 via correspondence with and publicly available reports from state departments of health. We linked this information to nursing home characteristics and used regression analysis to examine association between these characteristics and the likelihood of having a documented COVID‐19 case. RESULTS: Of 9,395 nursing homes in our sample, 2,949 (31.4%) had a documented COVID‐19 case. Larger facility size, urban location, greater percentage of African American residents, non‐chain status, and state were significantly (p<0.05) related to increased probability of having a COVID‐19 case. Five‐star rating, prior infection violation, Medicaid dependency, and ownership were not significantly related. CONCLUSIONS: COVID‐19 cases in nursing homes are related to facility location and size and not traditional quality metrics such as star rating and prior infection control citations. This article is protected by copyright. All rights reserved.


title: Reverse Genetics of Newcastle Disease Virus

text: Reverse genetics allows for the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique enables genetic manipulation and cloning of viral genomes, gene mutation through site-directed mutagenesis, along with gene insertion or deletion, among other studies. An in vitro infection-based system including the highly attenuated vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid, was successfully developed to rescue genetically modified Newcastle disease viruses in 1999. In this chapter, the materials and the methods involved in rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed mutagenesis and gene replacement techniques, are described in detail.


title: Renal Infarct in a COVID‐19 Positive Kidney‐Pancreas Transplant Recipient

text: The novel coronavirus disease 2019 (COVID‐19) is associated with increased risk of thromboembolic events, but the extent and duration of this hypercoagulable state remains unknown. We describe the first case report of renal allograft infarction in a 46‐year‐old kidney‐pancreas transplant recipient with no prior history of thromboembolism, who presented 26 days after diagnosis of COVID‐19. At the time of renal infarct, he was COVID‐19 symptom free and repeat test for SARS‐CoV‐2 was negative. This case report suggests that a hypercoagulable state may persist even after resolution of COVID‐19. Further studies are required to determine thromboprophylaxis indications and duration in solid organ transplant recipients with COVID‐19.


docid: iqmigvzk

title: Intertwined: Burnout and Wellbeing: Combating Physician Burnout: A Guide for Psychiatrists. Edited by Sheila LoboPrabhu, Richard F. Summers, and H. Steven Moffic; American Psychiatric Association Publishing; Washington, D.C.; 2020; ISBN 9731615372270; pp. 325; $ 60 (Paperback) Professional Well-Being: Enhancing Wellness Among Psychiatrists, Psychologists, and Mental Health Clinicians. By Grace W. Gengoux, Sanno E. Zack, Jennifer L. Derenne, Athena Robinson, Laura B. Dunn, and Laura Weiss Roberts; American Psychiatric Association Publishing; Washington, D.C., 2020; ISBN 9781615372294; pp. 286; $ 55 (Paperback)


title: The effect of human mobility and control measures on the COVID-19 epidemic in China

text: The ongoing COVID-19 outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions have been undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.


title: FDG-PET/CT imaging during the Covid-19 emergency: a southern Italian perspective

text: PURPOSE: To assess the impact of the Covid-19 pandemic on FDG-PET/CT work volume and to evaluate the occurrence of abnormal imaging findings suspicious or potentially diagnostic for interstitial pneumonia by Covid-19 infection in south Italy. METHODS: We retrospectively reviewed the number and the findings of FDG-PET/CT studies acquired between February and April 2020 during the Covid-19 pandemic at the University of Napoli Federico II. The number and the findings of FDG-PET/CT studies acquired in the corresponding period of 2019 were also assessed for direct comparison. RESULTS: The number of FDG-PET/CT studies performed during the pandemic (n = 299) and in the corresponding period of 2019 (n = 335) were comparable. The percentage of abnormal FDG-PET/CT findings, suspicious for interstitial pneumonia by Covid-19 infection, was significantly higher during the pandemic (9%) compared with that found in the corresponding period of 2019 (4%) (χ(2) 5.45, P = 0.02). No significant differences were observed in the distribution of Covid-19 reporting and data system (CO-RADS) classification and in the maximum standardized uptake value between the pandemic (2.6 ± 2.2) and the corresponding period of 2019 (3.2 ± 1.4). Of note, patients with abnormal imaging findings during the pandemic time had clinical data and/or laboratory tests negative for Covid-19 infection. CONCLUSION: Despite the restrictive medical measures for the emergency, the number of FDG-PET/CT studies was unchanged during the pandemic compared with the previous year. Our findings also indicate that Covid-19 infection was contained in our series of patients from southern Italy.


title: The effects of fever on hormone ghrelins, immunoglobulins, and heat shock protein 70 expression after swine flu vaccinations

text: For analyzing the changes in immunoglobulins, HSP70, ghrelin levels in blood samples were collected from volunteers vaccinated against swine flu before the vaccinations and on days 3, and 15, and 1 and 2 months after the vaccination in the presence or absence of fever associated with the it. The study included 11 subjects having developed a fever, and 13 subjects not having a fever, and 20 control subjects. Immunoglobulins were measured by nephelometry, and HSP70 and ghrelins by appropriate ELISA tests. The level of ghrelin was reduced, while the level of HSP70 was significantly increased in subjects who developed fevers. When temperatures were normalized, both levels were found similar to the control group. These results indicate that the increase in serum immunoglobulins levels associated with vaccinations, along with, elevations in HSP70 and reduced ghrelin levels associated with fever, may be the important parameters in the clinical evaluation and follow-up of treatments with vaccines.


title: Recent advances in the detection of respiratory virus infection in humans

text: Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.


title: Intestinal microbiota and chronic constipation

text: Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.


title: Pandemics and the Environmental Rebound Effect: Reflections from COVID-19

text: The irruption of the COVID-19 pandemic has raised concerns on sustainability issues. The pandemic has accelerated the implementation of technologies such as ICT and shifts in mobility behaviour. Such changes have the potential to reduce environmental burdens, but also to trigger large environmental rebound effects. This perspective article reflects on some emerging concerns on the socio-economic effects of a pandemic on the environment from a rebound effect perspective. Although the pandemic offers potential to improve the environmental conditions, it brings also a high risk to produce Jevons’ Paradox, i.e., increase environmental burdens rather than decrease them, as initially expected. Governments should be aware of these risks and assess the possibility to implement additional measures, like environmental taxation or limiting the use of resources, to help achieving sustainability targets.


title: Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

text: Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ∼58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.


title: Epidemiological characteristics and incubation period of 7,015 confirmed cases with Coronavirus Disease 2019 outside Hubei Province in China

text: BACKGROUND: Disease caused by SARS-CoV-2 broke out in Wuhan in December 2019. We utilized confirmed cases outside Hubei Province to analyze epidemiologic characteristics and evaluate the effect of traffic restrictions implemented in Hubei beginning on January 23, 2020. METHOD: Information on 7,015 confirmed cases from January 19 to February 8, 2020, in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit and diagnosis. We evaluated changes in incubation period and interval times. RESULTS: The average age of all cases was 44.24 years old. The median incubation period was 5 days and extended from 2 days on January 23 to 15 days on February 8. The proportion of imported cases decreased from 85.71% to 33.19% after January 23. In addition, the lengths of the intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time. CONCLUSION: Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurs among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.


title: SARS-CoV-2 and Diabetes: New Challenges for the Disease

text: A novel small enveloped RNA virus with the typical characteristic of the family to which it belongs, a crown, hence the name coronavirus, appeared in December 2019 in Wuhan, China, and subdued the world to its influence. The particular severity of the disease and higher mortality rates in patients with associated morbidities, including hypertension, obesity and diabetes, increases the concern over the consequences of this pandemic. In this review, the features of SARS-CoV-2 will be addressed, as well as the reasons why it poses a particular challenge to diabetic patients. We will also highlight the recent treatment strategies being explored to control this pandemic. Emerging evidence demonstrates that the correct management of diabetes in those patients infected with SARS-CoV-2 is of utmost importance for the viral disease progression, therefore, the importance of blood glucose control will also be addressed.


title: Cholesterol in relation to covid‐19: Should we care about it?

text: Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causing corona virus disease‐19 (COVID‐19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid‐lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID‐19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin‐converting enzyme 2 (ACE2) receptors for the S‐protein of SARS‐CoV‐2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol‐lowering therapies in reducing viral infectivity. In addition to their lipid‐lowering and plaque‐stabilisation effects, statins possess pleiotropic effects including anti‐inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS‐CoV‐2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID‐19.


title: Characterization and pathogenicity of Vero cell-attenuated porcine epidemic diarrhea virus CT strain

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV) has caused enormous economic losses to the global pig industry. Currently available PEDV vaccine strains have limited protective effects against PEDV variant strains. METHODS: In this study, the highly virulent epidemic virus strain CT was serially passaged in Vero cells for up to 120 generations (P120). Characterization of the different passages revealed that compared with P10 and P64, P120 had a higher viral titer and more obvious cytopathic effects, thereby demonstrating better cell adaptability. RESULTS: Pathogenicity experiments using P120 in piglets revealed significant reductions in clinical symptoms, histopathological lesions, and intestinal PEDV antigen distribution; the piglet survival rate in the P120 group was 100%. Furthermore, whole-genome sequencing identified 13 amino acid changes in P120, which might be responsible for the attenuated virulence of P120. CONCLUSIONS: Thus, an attenuated strain was obtained via cell passaging and that this strain could be used in preparing attenuated vaccines.


title: A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

text: Abstract The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness. Here, we evaluated various novel luciferase immunosorbent assays (LISA) based on nucleocapsid protein (NP) as well as fragments derived from spike protein (S) including subunit 1 (S1), N terminal domain (NTD), receptor-binding domain (RBD) and subunit 2 (S2) of S for the detection of MERS-CoV-specific IgG. Fusion proteins, including nanoluciferase (NLuc) and various fragments derived from the NP or S protein of MERS-CoV, were expressed in human embryonic kidney 293 T cells. LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins. Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR, commercial S1-based ELISA, and pseudovirus particle neutralization test (ppNT). Our results showed that the S1-, RBD-, and NP-LISAs were more sensitive than the NTD- and S2-LISAs for the detection of anti-MERS-CoV IgG. Furthermore, the S1-, RBD-, and NP-LISAs were more sensitive (by at least 16-fold) than the commercially available S1-ELISA. Moreover, the S1-, RBD-, and NP-LISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV (OC43, 229E, HKU1, NL63)-infected patients. More importantly, these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels, monkeys, and mice, among which the RBD-LISA exhibited excellent performance. The results of this study suggest that the novel MERS-CoV RBD- and S1- LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples. These assays have the potential to be used as serologic tests for the management and control of MERS-CoV infection.


docid: jorwzkld

title: Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review

text: COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic The disease continues to pose a major therapeutic challenge Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS) Cytokine release syndrome (or "cytokine storm") is likely to be a contributing factor to ARDS in many patients Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc) The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation Ultimately, the patient was downgraded from the ICU and discharged within days We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19 Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality-the cytokine storm This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19


title: Multisystem Resilience for Children and Youth in Disaster: Reflections in the Context of COVID-19

text: In the context of rising disasters worldwide and the challenges of the COVID-19 pandemic, this commentary considers the implications of findings in resilience science on children and youth for disaster preparation and response. The multisystem challenges posed by disasters are illustrated by the COVID-19 pandemic. We discuss the significance of disasters in the history of resilience science and the emergence of a unifying systems definition of resilience. Principles of a multisystem perspective on resilience and major findings on what matters for young people in disasters are delineated with reference to the pandemic. Striking parallels are noted in the psychosocial resilience factors identified at the level of individual children, families, schools, and communities. These parallels suggest that adaptive capacities associated with resilience in these interacting systems reflect interconnected networks and processes that co-evolved and may operate in concert. As resilience science moves toward integrated theory, knowledge, and applications in practice, particularly in disaster risk reduction and resilience promotion, more focus will be needed on multisystem and multidisciplinary research, communication, training, and planning.


title: Virus-induced exacerbations in asthma and COPD

text: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses. COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage. In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.


title: Concomitant multiple myeloma and probable phaeochromocytoma in a cat

text: CASE SUMMARY: Herein a drug-resistant IgG-lambda-type multiple myeloma associated with probable phaeochromocytoma in a cat is described. A 12-year-old cat presented with weakness, weight loss, progressive blindness and open-mouth breathing, in addition to polyuria and polydipsia of 2 months’ duration. Abdominal ultrasonography revealed a left adrenal mass. Phaeochromocytoma was suspected on the basis of cytology and was associated with systemic hypertension. Biochemistry showed hyperproteinaemia. Serum protein electrophoresis revealed a narrow spike in the gamma region, identified as IgG lambda type at immunoelectrophoresis. Bone marrow cytology revealed an infiltrate with numerous mature plasma cells. The cat was resistant to two different drugs for multiple myeloma and was euthanased 6 months later because of anorexia and persistent poor general condition. RELEVANCE AND NOVEL INFORMATION: This is the first clinical description of multiple myeloma associated with a suspected phaeochromocytoma in a cat.


title: Family‐based treatment via videoconference: Clinical recommendations for treatment providers during COVID‐19 and beyond

text: The necessity to employ distance‐based methods to deliver on‐going eating disorder care due to the novel coronavirus (COVID‐19) pandemic represents a dramatic and urgent shift in treatment delivery. Yet, TeleHealth treatments for eating disorders in youth have not been adequately researched or rigorously tested. Based on clinical experience within our clinic and research programs, we aim to highlight the common challenges clinicians may encounter in providing family‐based treatment (FBT) via TeleHealth for children and adolescents with anorexia nervosa and bulimia nervosa. We also discuss possible solutions and offer practical considerations for providers delivering FBT in this format. Additional research in TeleHealth treatment for eating disorders in youth may lead to improved access, efficiency, and effectiveness of FBT delivered via videoconferencing.


title: Gene Expression Analysis of Cardiovascular Diseases Novel Insights Into Biology and Clinical Applications

text: Although the contribution of genetics to complex cardiovascular diseases such as atherosclerosis has been accepted for quite some time, full and detailed knowledge of the individual causative genes has been elusive. With the advent of genomic technologies and methods, the necessary tools are now available to begin pinpointing the genes that contribute to disease susceptibility and progression. One approach being applied extensively in candidate gene discovery is gene expression analysis of human and animal tissues using microarrays. The genes identified by these genomic studies provide valuable insight into disease biology and represent the initial steps toward the development of diagnostic tests and therapeutic strategies that will substantially improve human health. This paper highlights the progress that has been made in using gene expression analysis cardiovascular genomic research and the potential for applying these findings in clinical medicine.


title: COVID-19 and Nicotine as a Mediator of ACE-2

text: α7-nAChR may upregulate ACE-2


title: Using pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs

text: In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs. 5’ and 3’ sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5’, 3’ and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5’, 3’ and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.


title: Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first reported to cause human infection in September 2012. In July 2013, the World Health Organization (WHO) International Health Regulations Emergency Committee determined that MERS-CoV did not meet criteria for a "public health emergency of international concern," but was nevertheless of "serious and great concern". This report summarizes epidemiologic information and provides updates to CDC guidance about patient evaluation, case definitions, travel, and infection control as of September 20, 2013.


title: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19

text: RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55–68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57–69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19–0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15–0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12–0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.


Teleproctoring in Vascular Surgery to Defy COVID-19 Travel Restrictions


title: Porcine Hemagglutinating Encephalomyelitis Virus

text: Publisher Summary This chapter provides an overview of the classification, description, hosts, key developments, diagnostic techniques, and diagnostic reagents for porcine hemagglutinating encephalomyelitis virus. Porcine hemagglutinating encephalomyelitis virus belongs to the family Coronaviridae; genus Coronavirus; and species Porcine hemagglutinating encephalomyelitis virus (HEV). Porcine hemagglutinating encephalomyelitis virus causes two distinct syndromes; one is known as vomiting and wasting disease, and the other involves encephalomyelitis. The hosts of porcine hemagglutinating encephalomyelitis virus are pigs. Vomiting and wasting disease and encephalomyelitis were initially reported as two separate diseases in Canada in the late 1950s. Porcine hemagglutinating encephalomyelitis virus was isolated in 1962, and the common etiology of the two syndromes was shown in 1969. The diagnostic techniques for porcine hemagglutinating encephalomyelitis virus are virus neutralisation (VN) and agar gel immunodiffusion (AGID).


title: Chikungunya virus: an update on antiviral development and challenges

text: Chikungunya virus (CHIKV) has re-emerged as a significant public health threat since the 2005 chikungunya fever epidemic in La Réunion. Driven by the medical importance of this virus, as well as the lack of approved antivirals, research into the field of CHIKV antivirals has recently intensified. Potential therapeutics that have been reported to show anti-CHIKV activity in vitro range from known broad-spectrum antivirals like chloroquine to novel strategies involving RNA silencing technology. Although most of the earlier efforts focused on compounds that target host components, some recent studies have reported viral targets such as nonstructural proteins. This article examines the reported in vitro and in vivo efficacies, as well as the therapeutic potential of these antiviral compounds.


title: Airport risk of importation and exportation of the COVID-19 pandemic

text: On March 11, 2020, the Director-General of the World Health Organization (WHO) characterized the spread of the coronavirus disease, COVID-19, as a pandemic on the basis of “alarming levels of spread and severity, and by the alarming levels of inaction.” Hence, it is urgent and imperative to evaluate the risk of COVID-19 for as many global locations as possible. This study calculates the relative risk of the importation and exportation of the COVID-19 virus. The study's most important contribution is the calculation of the overall relative risk of the importation and exportation of COVID-19 from every airport in local municipalities around the world, based on global spatial and mapping information. Three scenarios of air travel restriction are considered, and the change in the risk of importation and exportation of COVID-19 is calculated. The relative risk of importation and exportation of COVID-19 clearly shows that not only China, Europe, Middle East, and East Asia, but also the U.S., Australia, and countries in northeast Asia and Latin America are subject to risk. Further, a larger reduction in air travel through airports in a large part of the cumulative incidence area would lead to a gradual decrease in the risk flow. Importantly, the exportation risk of the disease from some airports in China, Iran, and European countries has a higher global spread than the importation risk during the pandemic stage. Therefore, every airport, or government with airports in their jurisdiction, should implement strict countermeasures. It is also indispensable for these countries to undertake countermeasures for COVID-19, such as home quarantine within each country and restricting infected or suspected individuals from flying on airplanes.


COVID-19 DIAGNOSTIC IMAGING: CAUTION NEED BEFORE THE END OF THE GAME.


title: Physical mapping of human cytomegalovirus genes: Identification of DNA sequences coding for a virion phosphoprotein of 71 kDa and a viral 65-kDa polypeptide

text: Abstract Polyadenylated RNA was isolated from fibroblast cultures infected with human cytomegalovirus (HCMV) strain AD169 during the late phase of viral replication. The RNA was selected by hybridization to a series of cosmid clones containing the entire viral genome in partially overlapping segments. Translation of this RNA in a reticulocyte cell-free system allowed the mapping of virus specific polypeptides. Nine polypeptides synthesized in vitro comigrated with major virion structural proteins. An in vitro-translated protein of 71 kDa was precipitated by a monoclonal antibody directed against the phosphorylated internal envelope protein of 71 kDa. The map coordinates of viral DNA coding for this phosphoprotein were localized by hybrid selection with subcloned DNA fragments, and the direction of transcription was determined by hybrid selection with single-stranded DNA cloned in bacteriophage vector M13mp9. An in vitro translation with size-fractionated RNA, combined with immunoprecipitation and Northern blot analyses, indicated that an mRNA of 4 kb encodes the 71-kDa phosphoprotein. An mRNA of the same size, map coordinates, and orientation was translated into an abundant 65-kDa polypeptide which had the same size as the major structural phosphoprotein of HCMV.


title: The impact of infectious diseases on hotel occupancy rate based on independent component analysis

text: Abstract The recent global outbreak of Influenza A (H1N1), or the more commonly known as swine flu, has negatively affected the tourism and hospitality industries in many countries. This article reports a study that applied independent component analysis, a novel statistical technique, to separate the dominant factors which determine the levels of hotel occupancy rates in Hong Kong. Empirical findings would provide useful insights on how the dynamic lodging demand reacts to epidemics based on the severity and duration of the events.


title: Intracerebral Hemorrhage and SARS-CoV-2: Association or Causation

text: BACKGROUND: Recent respiratory infection including SARS-CoV-2 is an independent risk factor for acute cerebrovascular disease. PURPOSE: There have been reports linking haemorrhagic strokes to SARS-CoV-2 infection during this pandemic, which lead us to evaluate if SARS-CoV-2 infection could be associated with increased risk of intracerebral haemorrhage (ICH). METHODS: A retrospective observational study evaluating all stroke cases admitted in our centre in the past one month. RESULTS: More than half (56%) had ICH, compared to 22% last year. Two patients with ICH were SARS-CoV-2 positive and they had no or mild respiratory symptoms and had higher occurrence of renal dysfunction. CONCLUSION: There could be possible association between ICH and SARS-CoV-2 infections. However, a prospective study with larger sample size is needed to elucidate the pathogenesis.


title: One world, one health: Humans, animals and the environment are inextricably linked—a fact that needs to be remembered and exploited in our modern approach to health

text: From the point of view that all organisms and the environment share one health, expending effort to address the needs of animals and ecosystems might pay better dividends for human health in the longer term.


title: Clinical characteristics of children with COVID-19: a rapid review and meta-analysis.

text: Background Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1,667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever [48%, 95% confidence interval (CI): 39%, 56%] and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% (95% CI: 8%, 22%) of children which is different from adult patients. 66% (95% CI: 55%, 77%) of children had abnormal findings in CT imaging. Conclusions Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.


docid: crptyvck

title: ECMO for COVID-19 associated severe ARDS and risk of thrombosis


Burn patients’ management during the COVID-19 pandemic: An institutional report from the Mohammed Vth Teaching Armed Forces Hospital in Morocco


title: Living with Bats: The Case of Ve Golokuati Township in the Volta Region of Ghana

text: Transmission of zoonotic pathogens from bats to humans through direct and indirect contact with bats raises public apprehension about living close to bats. In the township of Ve Golokuati in Ghana, several “camps” of Epomophorus gambianus roost in fruit trees that provide ecosystems services for residents. This study explored human-bat interaction in the township and the potential risks of disease transmission from bats to humans. Data were derived through questionnaire administration and participatory appraisal approach involving focus group discussions, participatory landscape mapping, and transect walk. The study found that most human activities within the township, such as petty-trading, domestic chores, and children's outdoor recreation, exposed people to bats. Though there have been no reported cases of disease spillover from bats to humans from the perspective of residents and from medical records, respondents whose activities brought them closer to bats within the township were found to be more likely to experience fevers than those who do not interact with bats frequently. The study recommends education of community members about the potential risks involved in human-bat interactions and makes suggestions for reducing the frequent interactions with and exposure to bats by humans.


title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia

text: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3′ end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3′ end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.


title: Aerosol Dispersion During Mastoidectomy and Custom Mitigation Strategies for Otologic Surgery in the COVID-19 Era

text: OBJECTIVE: To investigate small-particle aerosolization from mastoidectomy relevant to potential viral transmission and to test source-control mitigation strategies. STUDY DESIGN: Cadaveric simulation. SETTING: Surgical simulation laboratory. METHODS: An optical particle size spectrometer was used to quantify 1- to 10-µm aerosols 30 cm from mastoid cortex drilling. Two barrier drapes were evaluated: OtoTent1, a drape sheet affixed to the microscope; OtoTent2, a custom-structured drape that enclosed the surgical field with specialized ports. RESULTS: Mastoid drilling without a barrier drape, with or without an aerosol-scavenging second suction, generated large amounts of 1- to 10-µm particulate. Drilling under OtoTent1 generated a high density of particles when compared with baseline environmental levels (P < .001, U = 107). By contrast, when drilling was conducted under OtoTent2, mean particle density remained at baseline. Adding a second suction inside OtoTent1 or OtoTent2 kept particle density at baseline levels. Significant aerosols were released upon removal of OtoTent1 or OtoTent2 despite a 60-second pause before drape removal after drilling (P < .001, U = 0, n = 10, 12; P < .001, U = 2, n = 12, 12, respectively). However, particle density did not increase above baseline when a second suction and a pause before removal were both employed. CONCLUSIONS: Mastoidectomy without a barrier, even when a second suction was added, generated substantial 1- to 10-µm aerosols. During drilling, large amounts of aerosols above baseline levels were detected with OtoTent1 but not OtoTent2. For both drapes, a second suction was an effective mitigation strategy during drilling. Last, the combination of a second suction and a pause before removal prevented aerosol escape during the removal of either drape.


COVID-19 Pandemic and Nationwide Lockdown – Implications of the Double Trouble on Radiotherapy Practice in India