title: Vaccines for the 21st century

text: In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure‐based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines.


docid: cgdrcjfq

title: Breast Cancer Management Guidelines During COVID-19 Pandemic

text: The coronavirus disease (COVID-19) pandemic in 2020 has brought about complex challenges in healthcare delivery. With the new rules of lockdown and social distancing and with resources diverted to the management of COVID-19, there are difficulties in continuing usual cancer care. Patients are at risk of contracting COVID-19 with a high chance of patient to healthcare transmission and vice versa. Hospital visits, investigations and all modalities of treatment have potential complications that put patients at risk, some more than others. In this situation, there is a need to change our approach in the management of breast cancer to deliver it safely. We present modified guidelines based on the available consensus statements and evidence.


title: Epidemiology and risk factors for severe respiratory syncytial virus infections requiring pediatric intensive care admission in Hong Kong children

text: PURPOSE: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in young children. However, there are limited data on severe RSV infection requiring pediatric intensive care unit (PICU) admission. This retrospective study described features of RSV-associated PICU admissions in Hong Kong and investigated factors for mortality and duration of PICU stay. METHODS: Children with laboratory-confirmed RSV infection and admitted to the PICUs of all eight government hospitals in Hong Kong between January 2009 and June 2011 were identified from computerized auditing systems and PICU databases. RSV in respiratory samples was detected by direct immunofluorescence and/or viral culture. The relationships between mortality and PICU duration and demographic and clinical factors were analyzed. RESULTS: A total of 118 (2.4 %) PICU admissions were identified among 4,912 RSV-positive pediatric cases in all hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher between October and March. Eight (6.8 %) patients died, but only two were infants. RSV-associated mortality was related to prior sick contact, presence of older siblings, neurodevelopmental conditions, chromosomal and genetic diseases, and bacterial co-infections, but none was significant following logistic regression analyses (odds ratio 9.36, 95 % confidence interval 0.91–96.03 for prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for the duration of PICU admission (β = 0.218, p = 0.017). CONCLUSIONS: The majority of RSV-infected children do not require PICU support. There is winter seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is the only risk factor for RSV-associated mortality, whereas the presence of chronic lung disease is associated with longer PICU stay. The current risk-based approach of RSV prophylaxis may not be effective in reducing severe RSV infections.


title: COVID-19 Can Catalyze the Modernization of Medical Education

text: Amid the coronavirus disease (COVID-19) crisis, we have witnessed true physicianship as our frontline doctors apply clinical problem-solving to an illness without a textbook algorithm. Yet, for over a century, medical education in the United States has plowed ahead with a system that prioritizes content delivery over problem-solving. As resident trainees, we are acutely aware that memorizing content is not enough. We need a preclinical system designed to steer early learners from “know” to “know how.” Education leaders have long advocated for such changes to the medical school structure. For what may be the first time, we have a real chance to effect change. In response to the COVID-19 pandemic, medical educators have scrambled to conform curricula to social distancing mandates. The resulting online infrastructures are a rare chance for risk-averse medical institutions to modernize how we train our future physicians—starting by eliminating the traditional classroom lecture. Institutions should capitalize on new digital infrastructures and curricular flexibility to facilitate the eventual rollout of flipped classrooms—a system designed to cultivate not only knowledge acquisition but problem-solving skills and creativity. These skills are more vital than ever for modern physicians.


title: Single nucleotide polymorphisms in immune response genes in acute Q fever cases with differences in self-reported symptoms

text: Genes involved in human immune response are well recognized to influence the clinical course of infection. The association of host genetics with susceptibility to and severity of clinical symptoms in acute Q fever was investigated. Single nucleotide polymorphisms (SNPs) in the IFNG (rs2430561/rs1861493), STAT1 (rs1914408), and VDR (rs2228570) genes were determined in 85 patients from the 2007 Dutch acute Q fever outbreak, and a symptom score was calculated. IFNG rs1861493 showed a significant association with the symptom score; IFNG rs2430561 showed a similar trend. These SNPs were then used to reproduce results in a 2009 outbreak population (n = 123). The median symptom score differed significantly in both populations: 2 versus 7. The significant association of IFNG rs1861493 with symptom score in the first population was not reproduced in the second population. We hypothesize that individuals in the second outbreak were exposed to a higher Coxiella burnetii dose compared to the first, which overruled the protection conferred by the A-allele of IFNG rs1861493 in the first population.


title: Oral Immunization using Tuber Extracts from Transgenic Potato Plants Expressing Rabbit Hemorrhagic Disease Virus Capsid Protein

text: Rabbit hemorrhagic disease, which is caused by a calicivirus, is a lethal infection of adult animals that is characterized by acute liver damage and disseminated intravascular coagulation. In this study, we report the production of the major structural protein VP60 of rabbit hemorrhagic disease virus in transgenic tubers of potato plants and its use as an oral immunogen in rabbits.


title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR

text: Since December 2019, the coronavirus disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2 has rapidly spread to almost every nation in the world. Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. The ARTIC primer set amplifies 98 amplicons, which are separated only in two PCRs, across a nearly entire viral genome. The original primer set and protocol showed a fairly small amplification bias when clinical samples with relatively high viral loads were used. However, when sample’s viral load was low, several amplicons, especially amplicons 18 and 76, exhibited low coverage or complete dropout. We have determined that these dropouts were due to a dimer formation between the forward primer for amplicon 18, 18_LEFT, and the reverse primer for amplicon 76, 76_RIGHT. Replacement of 76_RIGHT with an alternatively designed primer was sufficient to produce a drastic improvement in coverage of both amplicons. Based on this result, we replaced 12 primers in total in the ARTIC primer set that were predicted to be involved in 14 primer interactions. The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network’s original (V1) and modified (V3) primer set.


title: The Role of Infection in Interstitial Lung Diseases A Review

text: Interstitial lung disease (ILD) comprises an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic, and clinical manifestations. There are ILDs with known causes and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD, but many exhibit gradual progression with an unpredictable clinical course in individual patients, as seen in idiopathic pulmonary fibrosis and the phenomenon of “acute exacerbation”(AE). Given the often poor prognosis of these patients, the search for a reversible cause of respiratory worsening remains paramount. Infections have been theorized to play a role in ILDs, both in the pathogenesis of ILD and as potential triggers of AE. Research efforts thus far have shown the highest association with viral pathogens; however, fungal and bacterial organisms have also been implicated. This review aims to summarize the current knowledge on the role of infections in the setting of ILD.


docid: vldknsrm

title: Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension

text: Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the primary causes of severe pulmonary hypertension. In order to identify long noncoding RNAs (lncRNAs) that may be involved in the development of CTEPH, comprehensive lncRNA and messenger RNA (mRNA) profiling of endothelial tissues from the pulmonary arteries of CTEPH patients was conducted with microarray analysis. Differential expression of 185 lncRNAs was observed in the CTEPH tissues compared with healthy control tissues. Further analysis identified 464 regulated enhancer-like lncRNAs and overlapping, antisense or nearby mRNA pairs. Coexpression networks were subsequently constructed and investigated. The expression levels of the lncRNAs, NR_036693, NR_027783, NR_033766 and NR_001284, were significantly altered. Gene ontology and pathway analysis demonstrated the potential role of lncRNAs in the regulation of central process, including inflammatory response, response to endogenous stimulus and antigen processing and presentation. The use of bioinformatics may help to uncover and analyze large quantities of data identified by microarray analyses, through rigorous experimental planning, statistical analysis and the collection of more comprehensive data regarding CTEPH. The results of the present study provided evidence which may be helpful in future studies on the diagnosis and management of CTEPH.


title: Bronchiectasis in Children: Current Concepts in Immunology and Microbiology

text: Bronchiectasis is a complex chronic respiratory condition traditionally characterized by chronic infection, airway inflammation, and progressive decline in lung function. Early diagnosis and intensive treatment protocols can stabilize or even improve the clinical prognosis of children with bronchiectasis. However, understanding the host immunologic mechanisms that contribute to recurrent infection and prolonged inflammation has been identified as an important area of research that would contribute substantially to effective prevention strategies for children at risk of bronchiectasis. This review will focus on the current understanding of the role of the host immune response and important pathogens in the pathogenesis of bronchiectasis (not associated with cystic fibrosis) in children.


The presence of virus significantly associates with chronic rhinosinusitis disease severity


title: Diagnostic and therapeutic potential of shark variable new antigen receptor (VNAR) single domain antibody

text: Abstract Conventional monoclonal antibodies (mAbs) have been widely used in research and diagnostic applications due to their high affinity and specificity. However, multiple limitations, such as large size, complex structure and sensitivity to extreme ambient temperature potentially weaken the performance of mAbs in certain applications. To address this problem, the exploration of new antigen binders is extensively required in relation to improve the quality of current diagnostic platforms. In recent years, a new immunoglobulin-based protein, namely variable domain of new antigen receptor (VNAR) was discovered in sharks. Unlike conventional mAbs, several advantages of VNARs, include small size, better thermostability and peculiar paratope structure have attracted interest of researchers to further explore on it. This article aims to first present an overview of the shark VNARs and outline the characteristics as an outstanding new reagent for diagnostic and therapeutic applications.


Rotavirus and Coronavirus Vaccines


title: PEACOCK: A Map-Based Multitype Infectious Disease Outbreak Information System

text: A map-based infectious disease outbreak information system, called PEACOCK, that provides three types of necessary infectious disease outbreak information is presented. The system first collects the infectious disease outbreak statistics from the government agencies and displays the number of infected people and infection indices on the map. Then, it crawls online news articles for each infectious disease and displays the number of mentions of each disease on the map. Users can also search for news articles regarding the disease. Finally, it retrieves the portal search query data and plots the graphs of the trends. It divides the risk into three levels (i.e., normal, caution, and danger) and visualizes them using different colors on the map. Users can access infectious disease outbreak information accurately and quickly using the system. As the system visualizes the information using both a map and various types of graphs, users can check the information at a glance. This system is in live at http://www.epidemic.co.kr/map.


title: Development of nonhuman adenoviruses as vaccine vectors

text: Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclinical and clinical studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clinical use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addition to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination.


title: An Amphipathic α-Helix Controls Multiple Roles of Brome Mosaic Virus Protein 1a in RNA Replication Complex Assembly and Function

text: Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol)) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic α-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol) accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol) accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.


title: Multiple Acute Ischemic Strokes in a COVID-19 Patient: a Case Report

text: We describe a case of a 47-year-old Italian, immunocompromised, and obese woman infected by COVID-19 presenting with fever (39.6 °C) and respiratory symptoms. Neurological examination was normal. Chest CT findings consist of bilateral interstitial pneumonia (visual score extension: 30%). The patient was treated with antiviral drugs and anti-inflammatory drugs with supportive care. Seven days after admission to Covid-19 Unit, the patient rapidly developed worsening respiratory failure and acute respiratory distress syndrome (ARDS). She suddenly developed partial left hemispheric syndrome. A new HRCT scan of her thorax revealed diffuse ground-glass opacities in both lungs (visual score extension: 90%). Brain CT performed 2 h after sudden-onset left-sided weakness showed subtle low attenuation within the right insular ribbon and frontal lobe (ASPECT Score 8). Multiphasic CT angiography (MCTA) demonstrated occlusion of both the dominant inferior division of the right middle cerebral artery and the A2 segment of the right anterior cerebral artery. After 24 h, her pupils became dilated and unreactive, and brain CT demonstrated large bilateral infarctions of both the cerebellar and cerebral hemispheres. She had a rapid progression of interstitial pneumonia from COVID-19, developed multiple strokes, and died 1 day later. SARS-CoV-2 infection seems to predispose pluripathological subjects to cerebrovascular complications.


title: Interferon alfacon1 is an inhibitor of SARS-corona virus in cell-based models

text: Abstract Preliminary data examining interferon alfacon1 treatment of SARS-CoV (severe acute respiratory syndrome-corona virus)-infected patients suggests this therapy is well tolerated and of therapeutic benefit. We report herein that interferon alfacon1, has potent in vitro antiviral activity against SARS-CoV. In a cytopathic effect protection (CPE) assay, interferon alfacon1 inhibited the generation of CPE in a dose-dependent manner with an IC50 of 0.001μg/ml, a clinically achievable level. Furthermore, interferon alfacon1 also demonstrated significant antiviral activity in yield reduction and plaque reduction assays. The in vitro antiviral activity of interferon alfacon1 against SARS-CoV suggests continued evaluation of interferon alfacon1 as a therapeutic treatment for patients infected with SARS-CoV.


title: Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine

text: BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2–9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2–6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1–0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2823-9) contains supplementary material, which is available to authorized users.


title: Aerosol Sampling in a Hospital Emergency Room Setting: A Complementary Surveillance Method for the Detection of Respiratory Viruses

text: This study aimed to evaluate environmental air sampling as an alternative form of active surveillance for respiratory pathogens in clinical settings. Samples were collected from three locations in the Emergency Department at Duke University Hospital Systems from October 2017 to March 2018. Of the 44 samples collected, 12 were positive for known respiratory pathogens including influenza A, influenza D, and adenovirus. Results suggest bioaerosol sampling may serve as a complement to active surveillance in clinical settings. Additionally, since respiratory viruses were detected in aerosol samples, our results suggest that hospital infection control measures, including the use of N95 respirators, could be used to limit the spread of infectious viruses in the air.


The Next Influenza Pandemic: Will we be Ready to Care for Our Children?


title: Family Coronaviridae

text: Publisher Summary This chapter focuses on Coronaviridae family whose two subfamilies include Coronavirinae and Torovirinae. The member genera include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, Torovirus, and Bafinivirus. The members of the family Coronaviridae are enveloped and positive stranded RNA viruses of three classes of vertebrates, which include corona- and toroviruses for mammals, coronaviruses for birds, and bafiniviruses for fishes. The nucleocapsids are helical and can be released from the virion by treatment with detergents. Where the coronavirus nucleocapsid appears to be loosely wound, those of the Torovirinae are distinctively tubular. The entire replication cycle takes place in the cytoplasm and involves the production of full-length and subgenome-sized (sg) minus-strand RNA intermediates with the viral genome serving both as mRNA for the replicase polyproteins and as a template for minus-strand synthesis. Members of the family Coronaviridae all seem to share two envelope protein species, the membrane (M) and spike (S) proteins. Similarities in size, predicted structures and presumed function(s) suggest a common ancestry, and the remote, but significant sequence similarities observed for toro-, bafini-, and (to lesser extent) coronavirus S proteins lend further support to this view. The replicase polyproteins of the Coronaviridae comprise a number of characteristic domains arranged in a conserved order.


title: Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan

text: Abstract Introduction Infectious mononucleosis (IM) is a common viral infection that typically causes fever, pharyngitis, and lymphadenopathy in young patients. The Epstein-Barr virus (EBV) is the most common cause of IM, followed by cytomegalovirus (CMV). Given that serological testing is associated with limitations regarding its accuracy, availability, and time to receive results, clinical differentiation based on symptoms, signs, and basic tests would be useful. We evaluated whether clinical findings could be used to differentiate EBV-IM from CMV-IM. Methods In this single-center retrospective case-control study, we evaluated >14-year-old patients with serologically confirmed EBV-IM or CMV-IM during 2006–2017. We compared the patients’ symptoms, physical findings, blood counts, and serum biomarkers to create three regression models: model 1 (symptoms and signs), model 2 (model 1 plus sonographic hepatosplenomegaly and blood counts), and model 3 (model 2 plus hepatobiliary biomarkers). Results Among the 122 patients (72.6%) with EBV-IM and 46 patients (27.4%) with CMV-IM, the median age was 25 years and 82 patients (48.8%) were male. The median age was 10 years older in the CMV-IM group (p < 0.001) and the median interval from onset to visit was 5 days longer in the CMV-IM group (p < 0.001). Logistic regression revealed that EBV-IM was predicted by younger age, short onset-to-visit interval, lymphadenopathy, tonsillar white coat, hepatosplenomegaly, atypical lymphocytosis, and elevations of lactate dehydrogenase and gamma-glutamyl transferase. All regression models had areas under the curve of >0.9. Conclusion History and physical findings, especially when used with atypical lymphocytosis and sonographic hepatosplenomegaly, can help physicians differentiate EBV-IM from CMV-IM.


title: Pulmonary fibrosis induced by H5N1 viral infection in mice

text: BACKGROUND: Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus. METHODS: Eight-week-old BALB/c mice were inoculated intranasally with 1 × 10(1 )MID(50 )of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation. RESULTS: H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice. CONCLUSION: Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.


title: Novel corona virus disease (COVID-19) awareness among the dental interns, dental auxiliaries and dental specialists in Saudi Arabia: A nationwide study

text: BACKGROUND: Dental health care workers (DHCW's) are invariably at a higher risk of contracting COVID-19. The objectives were; to investigate the current knowledge on COVID-19 among the DHCW's; and to conduct quasi-experiment among the DHCW's who were unaware of the disseminated COVID-19 information. METHODS: A nationwide cross-sectional study targeting dental interns, auxiliaries, and specialists with a two-staged cluster sampling technique was performed. A 17-item questionnaire was subjected to reliability and validity tests before being administered. The participants for quasi-experiment were separated from the original sample after their initial response. Chi-square test assessed responses to knowledge statements between the participants. Difference in mean knowledge scores between the categories of DHCW's and sources of COVID-19 information was assessed using ANOVA. Data from the quasi experiment (pre vs post knowledge intervention) was subjected to paired t-test. Percentage of DHCWs providing correct or wrong responses to each knowledge statement at baseline and after 7 days were compared using McNemar test. RESULTS: The overall sample consisted of 706 (N) participants, and the DHCW's with no prior knowledge on COVID-19 (N = 206) were part of the quasi experiment. Findings from cross-sectional study revealed that knowledge was significantly (p < 0.05) related to the qualification level (interns vs auxiliaries vs specialists). However, the difference in the source of information (WHO/CDC vs Journal articles vs MoH) did not demonstrate any effect. Number of participants with correct responses to knowledge questions had significantly (p < 0.05) increased after intervention. Also, the overall mean knowledge score (10.74 ± 2.32 vs 12.47 ± 1.68; p < 0.001) had increased significantly after the intervention. CONCLUSION: In conclusion, the basic knowledge on COVID-19 among the DHCW's in Saudi Arabia is acceptable. Timely dissemination of information by the Ministry of Health, Saudi Arabia had a positive impact on the COVID-19 knowledge score of the DHCW's.


title: Rearrangement of viral sequences in cytopathogenic pestiviruses

text: Abstract Two cytopathogenic isolates of bovine viral diarrhea virus (cpBVDV) have been analyzed. For both viruses two regions of their genomic RNAs were found to be duplicated and rearranged. The viral genomes contain a small duplicated element (SD) derived from the genomic 5' end far downstream of its original context. This sequence is followed by a larger duplication which encompasses the region coding for the protein p80(LD), a molecular marker for cpBVDV. The SD element codes for the viral protease p20. In the case of the viruses analyzed here the aminoterminus of p80 is generated by autoproteolytic removal of the preceding SD-encoded protease. For one of the cpBVDV isolates a specific fusion protein (p28) could be identified which is composed of p20 and part of p10, another viral protein. Molecular characterization of the respective noncytopathogenic counterpart revealed that duplication and rearrangement of sequences as well as the expression of p28 and p80 are specific for the cytopathogenic virus.


title: Nasopharyngeal Pneumococcal Density during Asymptomatic Respiratory Virus Infection and Risk for Subsequent Acute Respiratory Illness

text: Increased nasopharyngeal pneumococcal (Streptococcus pneumoniae) colonization density has been associated with invasive pneumococcal disease, but factors that increase pneumococcal density are poorly understood. We evaluated pneumococcal densities in nasopharyngeal samples from asymptomatic young children from Peru and their association with subsequent acute respiratory illness (ARI). Total pneumococcal densities (encompassing all present serotypes) during asymptomatic periods were significantly higher when a respiratory virus was detected versus when no virus was detected (p<0.001). In adjusted analyses, increased pneumococcal density was significantly associated with the risk for a subsequent ARI (p<0.001), whereas asymptomatic viral detection alone was associated with lower risk for subsequent ARI. These findings suggest that interactions between viruses and pneumococci in the nasopharynx during asymptomatic periods might have a role in onset of subsequent ARI. The mechanisms for these interactions, along with other potentially associated host and environmental factors, and their role in ARI pathogenesis and pneumococcal transmission require further elucidation.


title: Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study

text: Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019. Although previous studies have described the clinical aspects of COVID-19, few studies have focused on the early detection of severe COVID-19. Therefore, this study aimed to identify the predictors of severe COVID-19 and to compare clinical features between patients with severe COVID-19 and those with less severe COVID-19. Patients admitted to designated hospital in the Henan Province of China who were either discharged or died prior to February 15, 2020 were enrolled retrospectively. Additionally, patients who underwent at least one of the following treatments were assigned to the severe group: continuous renal replacement therapy, high-flow oxygen absorption, noninvasive and invasive mechanical ventilation, or extracorporeal membrane oxygenation. The remaining patients were assigned to the non-severe group. Demographic information, initial symptoms, and first visit examination results were collected from the electronic medical records and compared between the groups. Multivariate logistic regression analysis was performed to determine the predictors of severe COVID-19. A receiver operating characteristic curve was used to identify a threshold for each predictor. Altogether,104 patients were enrolled in our study with 30 and 74 patients in the severe and non-severe groups, respectively. Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×10(9)/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Thus, our results could be helpful in the early detection of patients at risk for severe illness, enabling the implementation of effective interventions and likely lowering the morbidity of COVID-19 patients.


title: Influence of 3D topography on tribological behavior of grinding wheel

text: Abstract Grinding is extensively used as surface generation process in finishing operations, which makes it imperative that the generated surface adheres closely to strict quality check norms failing which the component will be rejected incurring a loss to the industry. To ensure the intended surface quality falls within tolerances, the grinding wheel plays an important role as an abrasive tool. The finished surface is a direct outcome of grinding wheel topography and its various microscopic interactions with the surface creating a compelling need for in-depth understanding. Study and characterization of grinding wheel topography in the present paper aim to understand the behavior of forces in the contact area. Due to stochastic abrasive grain distribution and quasi-static surface wear, 3-dimensional parameters hold a better physical significance in explaining the nature of microscopic interactions and their impact on the behavior of forces. Experiments are performed in a manner to wear out grinding wheels of the same specification with varying number of passes in an attempt to highlight the influence of varying topography on tribological interactions in the grind zone. The variation in topography at a specific interval of time is captured using a confocal laser scanning microscope and further processed for surface characterization whereas forces are captured using a dynamometer. SEM micrographs are presented to understand the type of wear on the wheel surface. The outcome of present paper enables to understand and report the surface interactions quantified in terms of cutting, ploughing and rubbing whereas surface parameters are characterized as per ISO 25178. The reasoning behind variations during surface interactions was discussed and interpretations were reported.


title: Early chest computed tomography to diagnose COVID-19 from suspected patients: A multicenter retrospective study

text: Abstract Objective The purpose of this study was to distinguish the imaging features of COVID-19 from those of other chest infectious diseases and evaluate the diagnostic value of chest CT for suspected COVID-19 patients. Methods Adult patients suspected of COVID-19 aged >18 years who underwent chest CT scans and reverse-transcription polymerase chain reaction (RT-PCR) tests within 14 days of symptom onset were enrolled. The enrolled patients were confirmed and grouped according to the results of the RT-PCR tests. The basic demographics, single chest CT features, and combined chest CT features were analyzed for the confirmed and nonconfirmed groups. Results A total of 130 patients were enrolled, with 54 testing positive and 76 testing negative. The typical CT imaging features of the positive group were ground glass opacities (GGOs), the crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally and close to the lower lungs or the pleura. When features were combined, GGOs with bilateral pulmonary distribution and GGOs with pleural distribution were more common among the positive patients, found in 31 (57.4%) and 30 patients (55.6%), respectively. The combinations were almost all statistically significant (P < .05), except for the combination of GGOs with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations was approximately 90%. Conclusions The combinations with GGOs could be useful in the identification and differential diagnosis of COVID-19, alerting clinicians to isolate patients for prompt treatment and repeat RT-PCR tests until the end of incubation.


title: Detection of feline kobuviruses in diarrhoeic cats, Italy

text: Abstract Kobuviruses have been identified in the enteric tract of several mammalian species but their role as enteric pathogens is still not defined. In this study, feline kobuviruses were found in 13.5% of cats with diarrhoea, but not in asymptomatic animals. In the full-length genome, one such strains, TE/52/13/ITA, displayed the highest nucleotide identity (96.0%) to the prototype strain FK-13. These results provide firm evidence that kobuviruses are common constituents of feline enteric viroma and that they are not geographically restricted to the Asian continent, where they were first signalled.


title: Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

text: Interferon (IFN)-αs bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-α treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jak1 phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C (PKC) δ to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV-1 infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation of pkr and 2′5′-oas, genes associated with mediating the antiviral activities of IFN-αs. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with functional properties associated with antimicrobial activities.


title: Peptide Vaccine: Progress and Challenges

text: Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.


title: Human pegivirus detected in a patient with severe encephalitis using a metagenomic pan-virus array

text: Abstract We have used a metagenomic microarray to detect genomic RNA from human pegivirus in serum and cerebrospinal fluid from a patient suffering from severe encephalitis. No other pathogen was detected. HPgV in cerebrospinal fluid during encephalitis has never been reported before and its prevalence in cerebrospinal fluid needs further investigation.


title: Public Health Is Essential: COVID-19’s Learnable Moment for Medical Education

text: The COVID-19 pandemic, an unprecedented challenge for this generation of physicians and for the health care system, has reawakened calls to strengthen the United States’ public health systems. This global event is also a “learnable moment” for medical education—an opportunity to decisively incorporate public health, including public health systems, through the continuum of medical education. Although medical educators have made progress in integrating public health content into medical curricula, “public health” is not a phrase that is consistently used in curricular standards, and public health colleagues are not identified as unique and essential partners to improve and protect health. The COVID-19 crisis has demonstrated how a strong public health system is necessary to support the health of patients and populations, as well as the practice of medicine. Partnerships between medical and public health communities, through individual- and population-based interventions, can also more effectively combat more common threats to health, such as chronic diseases, health inequities, and substance abuse. To achieve a more effective medicine–public health relationship in practice, curricula across the continuum of medical education must include explanations of public health systems, the responsibilities of physicians to their local and state governmental public health agencies, and opportunities for collaboration. Medical education should also prepare physicians to advocate for public health policies, programs, and funding in order to improve and protect the health of their patients and communities. Pandemic COVID-19 demonstrates with laser focus that all physicians are part of public health systems and that public health content has a distinct and critical place across the continuum of medical education to prepare physicians to participate in, collaborate with, and advocate for public health systems.


Does online pornography influence the sexuality of adolescents during COVID-19?


title: HIV-1 Protease Catalytic Efficiency Effects Caused by Random Single Amino Acid Substitutions

text: Protein evolution has occurred by successive fixation of individual mutations. The probability of fixation depends on the fitness of the mutation, and the arising variant can be deleterious, neutral, or beneficial. Despite its relevance, only few studies have estimated the distribution of fitness effects caused by random single mutations on protein function. The human immunodeficiency virus type 1 (HIV-1) protease was chosen as a model protein to quantify protein's tolerability to random single mutations. After determining the enzymatic activity of 107 single random mutants, we found that 86% of single mutations were deleterious for the enzyme catalytic efficiency and 54% lethal. Only 2% of the mutations significantly increased the catalytic efficiency of the enzyme. These data demonstrate the vulnerability of HIV-1 protease to single random mutations. When a second random mutagenesis library was constructed from an HIV-1 protease carrying a highly deleterious single mutation (D30N), a higher proportion of mutations with neutral or beneficial effect were found, 26% and 9%, respectively. Importantly, antagonist epistasis was observed between deleterious mutations. In particular, the mutation N88D, lethal for the wild-type protease, restored the wild-type catalytic efficiency when combined with the highly deleterious mutation D30N. The low tolerability to single random substitutions shown here for the wild-type HIV-1 protease contrasts with its in vivo ability to generate an adaptive variation. Thus, the antagonist epistasis between deleterious or lethal mutations may be responsible for increasing the protein mutational robustness and evolvability.


title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

text: Background Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.


title: Preanalytical Considerations for Joint Fluid Evaluation

text: Synovial fluid analysis is a key component of the minimum database needed to diagnose and manage primary and secondary articular joint disorders. Unfortunately, preanalytical variables can drastically alter samples submitted for evaluation to veterinary laboratories and it is considered the stage at which most laboratory error occurs. This article addresses common sources of preanalytical variability and error that are seen in veterinary medicine. With consistent quality control and reporting of specimens, downstream clinical decision making and management of patients can be accelerated and improved.


The One Health path to infectious disease prevention and resilience


Reducción de los ingresos por infarto agudo de miocardio con elevación del segmento ST en Cataluña durante la pandemia de COVID-19


title: Chapter 8 Virus Evolution and Genetics

text: Abstract Viruses are very diverse and they infect organisms from all domains of life and across all ecosystems, but related viruses often infect very different types of organisms, pointing to their very ancient origins. Three commonly proposed mechanisms for the origins of viruses are: Viruses descended from primitive precellular life forms; viruses are escaped cellular genetic elements; viruses devolved from more complex intracellular parasites. None of these theories easily explains the origins of all viruses and it is widely accepted that all viruses did not share a single common ancestor. Instead, distinct lineages of viruses probably evolved by different mechanism. There is also good evidence that viruses have shaped the evolution of their hosts, for at least hundreds of millions of years. While some virologists consider the ancient origins of viruses, others examine the forces that drive virus evolution today. Examples of ongoing virus evolution include: Cross-species jumps; decreased or increased virulence; emergence of drug resistance; escape from immune responses at the level of individuals and populations. Virus evolution is the outcome of two independent events. The first is genome mutation and the second is selection. Viruses with RNA genomes tend to have high mutation rates, but some appear to be evolutionarily stable nonetheless. Viruses have distinct phenotypes. For examples, some influenza viruses are highly virulent but others are much less so; influenza viruses also differ tremendously in their ability to be transmitted. Modern studies of virus genetics seek to correlate diverse phenotypes with specific genes and sequences. The ability to do reverse genetics is key to understanding viral genes. Reverse genetics involves cloning viral genomes, designing specific mutation, and introducing the mutated genomes back into cells to produce infectious particles whose phenotypes can then be measured.


title: Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection

text: We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.


title: Precision public health to inhibit the contagion of disease and move toward a future in which microbes spread health

text: Antimicrobial resistance continues to outpace the development of new chemotherapeutics. Novel pathogens continue to evolve and emerge. Public health innovation has the potential to open a new front in the war of “our wits against their genes” (Joshua Lederberg). Dense sampling coupled to next generation sequencing can increase the spatial and temporal resolution of microbial characterization while sensor technologies precisely map physical parameters relevant to microbial survival and spread. Microbial, physical, and epidemiological big data could be combined to improve prospective risk identification. However, applied in the wrong way, these approaches may not realize their maximum potential benefits and could even do harm. Minimizing microbial-human interactions would be a mistake. There is evidence that microbes previously thought of at best “benign” may actually enhance human health. Benign and health-promoting microbiomes may, or may not, spread via mechanisms similar to pathogens. Infectious vaccines are approaching readiness to make enhanced contributions to herd immunity. The rigorously defined nature of infectious vaccines contrasts with indigenous “benign or health-promoting microbiomes” but they may converge. A “microbial Neolithic revolution” is a possible future in which human microbial-associations are understood and managed analogously to the macro-agriculture of plants and animals. Tradeoffs need to be framed in order to understand health-promoting potentials of benign, and/or health-promoting microbiomes and infectious vaccines while also discouraging pathogens. Super-spreaders are currently defined as individuals who play an outsized role in the contagion of infectious disease. A key unanswered question is whether the super-spreader concept may apply similarly to health-promoting microbes. The complex interactions of individual rights, community health, pathogen contagion, the spread of benign, and of health-promoting microbiomes including infectious vaccines require study. Advancing the detailed understanding of heterogeneity in microbial spread is very likely to yield important insights relevant to public health.


title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages

text: We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.


title: FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity

text: Abstract The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5μg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11–21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14–21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.


title: An exercise in molecular epidemiology: Human rhinovirus prevalence and genetics

text: Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques for classifying new isolates of HRV were reported. The genetic change of this virus in specific populations over time is of great interest to understand the evolution and epidemiology of viruses. To facilitate the collections of HRV sequences over a number of years, a virology experiment was designed in which students test nasal lavage samples to look for HRV infection. Students will learn a variety of techniques including RNA isolation, cDNA synthesis, qPCR, and agarose gel electrophoresis as well as bioinformatic skills though examination of sequences from the HRV‐field isolates. Furthermore, students can look at symptom data from subjects to investigate correlations between symptom severity and factors such as stress and sleep patterns. Such information can be used to examine hypotheses regarding HRV mutation, symptom severity and epidemiology. BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Vol. 39, No. 6, pp. 457–458, 2011


title: COVID stress syndrome: Concept, structure, and correlates

text: BACKGROUND: Research shows that the COVID Stress Scales have a robust multifactorial structure, representing five correlated facets of COVID‐19‐related distress: (a) Fear of the dangerousness of COVID‐19, which includes fear of coming into contact with fomites potentially contaminated with SARSCoV2, (b) worry about socioeconomic costs of COVID‐19 (e.g., worry about personal finances and disruption in the supply chain), (c) xenophobic fears that foreigners are spreading SARSCoV2, (d) traumatic stress symptoms associated with direct or vicarious traumatic exposure to COVID‐19 (nightmares, intrusive thoughts, or images related to COVID‐19), and (e) COVID‐19‐related compulsive checking and reassurance seeking. These factors cohere to form a COVID stress syndrome, which we sought to further delineate in the present study. METHODS: A population‐representative sample of 6,854 American and Canadian adults completed a self‐report survey comprising questions about current mental health and COVID‐19‐related experiences, distress, and coping. RESULTS: Network analysis revealed that worry about the dangerousness of COVID‐19 is the central feature of the syndrome. Latent class analysis indicated that the syndrome is quasi‐dimensional, comprising five classes differing in syndrome severity. Sixteen percent of participants were in the most severe class and possibly needing mental health services. Syndrome severity was correlated with preexisting psychopathology and with excessive COVID‐19‐related avoidance, panic buying, and coping difficulties during self‐isolation. CONCLUSION: The findings provide new information about the structure and correlates of COVID stress syndrome. Further research is needed to determine whether the syndrome will abate once the pandemic has passed or whether, for some individuals, it becomes a chronic condition.


title: Placental pathology in COVID-19

text: Objectives: To describe histopathologic findings in the placentas of women with COVID-19 during pregnancy. Methods: Pregnant women with COVID-19 delivering between March 18, 2020 and May 5, 2020 were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. Results: 16 placentas from patients with SARS-CoV-2 were examined (15 with live birth in the 3rd trimester 1 delivered in the 2nd trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), including abnormal or injured maternal vessels, as well as delayed villous maturation, chorangiosis, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. Conclusions: Relative to controls, COVID-19 placentas show increased prevalence of features of maternal vascular malperfusion (MVM), a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.


title: When your cap matters: Structural insights into self vs non-self recognition of 5′ RNA by immunomodulatory host proteins

text: Cytosolic recognition of viral RNA is important for host innate immune responses. Differential recognition of self vs non-self RNA is a considerable challenge as the inability to differentiate may trigger aberrant immune responses. Recent work identified the composition of the RNA 5′, including the 5′ cap and its methylation state, as an important determinant of recognition by the host. Recent studies have advanced our understanding of the modified 5′ RNA recognition and viral antagonism of RNA receptors. Here, we will discuss RIG-I and IFIT proteins as examples of host proteins that detect dsRNA and ssRNA, respectively.


Public health centres in contemporary Japan


title: Mutational patterns correlate with genome organization in SARS and other coronaviruses

text: Abstract Focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (SARS), novel coronavirus SARS-CoV, in record time. Using cumulative skew diagrams, I found that mutational patterns in the SARS-CoV genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. These findings might be relevant for the development of sequence-based diagnostics and the design of agents to treat SARS.


title: A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease

text: Abstract Background The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. Method Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. Results Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. Conclusion Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19.


title: Clinical assessment of patients with smell and taste disorders

text: Clinical assessment of the patient who has smell and taste disorders requires understanding of the etiology of the olfactory and gustatory disorders. Available clinical tests of olfactory and gustatory systems allow detecting and measuring the degree of the sensory loss, but are unable to determine the cause and give neither prognostic information nor therapeutic guidance. With physical examination, however, clinical history can help to establish the diagnosis and guide the treatment if available. A clinician evaluating a patient who has smell and taste loss must understand that "taste" complaints usually are symptoms of an olfactory dysfunction. The distinction between true gustatory loss (bitter, sweet, salty, sour, or umami) and olfactory loss, the inability to perceive complex flavors of food, will help clarify the patient's diagnosis. Easy-to-administer tests are available for olfactory (eg, UPSIT) and gustatory testing (eg, spatial tests, taste sticks, tasting tablets). In rare circumstances, imaging studies (eg, MRI, CT) are indicated.


title: Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY(1)) residents' ACGME six core competencies: a 2-year study

text: OBJECTIVE: The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the ‘faculty development programme for teaching ACGME competencies.’ METHODS: During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. RESULTS: The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of ‘how to teach ACGME competencies.’ Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. CONCLUSIONS: According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical instructors also then subsequently apply these skills.


title: Recomendaciones sobre el tratamiento antitrombótico durante la pandemia COVID-19. Posicionamiento del Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología

text: Abstract The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy. Full English text available from: www.revespcardiol.org/en


title: Chest CT Features of COVID-19 in Rome, Italy

text: BACKGROUND: The standard for diagnosis of SARS-CoV-2 virus is reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of COVID-19 pneumonia. PURPOSE: To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with RT-PCR. METHODS: In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients with suspected COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were: chest CT with contrast medium performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as reference. Chest CT features were calculated in a subgroup of RT-PCR-positive and CT-positive patients. CT features of hospitalized patients and patient in home isolation were compared by using Pearson chi squared test. RESULTS: Our study population comprised 158 consecutive study participants (83 male and 75 female, mean age 57 y ±17). Fever was observed in 97/158 (61%), cough in 88/158 (56%), dyspnea in 52/158 (33%), lymphocytopenia in 95/158 (60%), increased C-reactive protein level in 139/158 (88%), and elevated lactate dehydrogenase in 128/158 (81%) study participants. Sensitivity, specificity, and accuracy of CT were 97% (60/62)[95% IC, 88-99%], 56% (54/96)[95% IC,45-66%] and 72% (114/158)[95% IC 64-78%], respectively. In the subgroup of RT-PCR-positive and CT-positive patients, ground-glass opacities (GGO) were present in 58/58 (100%), multilobe and posterior involvement were both present in 54/58 (93%), bilateral pneumonia in 53/58 (91%), and subsegmental vessel enlargement (> 3 mm) in 52/58 (89%) of study participants. CONCLUSION: The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripherally ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (> 3 mm). Chest CT sensitivity was high (97%) but with lower specificity (56%).


title: Cloning, expression and antiviral activity of IFNγ from the Australian fruit bat, Pteropus alecto

text: Bats are natural reservoir hosts to a variety of viruses, many of which cause morbidity and mortality in other mammals. Currently there is a paucity of information regarding the nature of the immune response to viral infections in bats, partly due to a lack of appropriate bat specific reagents. IFNγ plays a key role in controlling viral replication and coordinating a response for long term control of viral infection. Here we describe the cloning and expression of IFNγ from the Australian flying fox, Pteropus alecto and the generation of mouse monoclonal and chicken egg yolk antibodies specific to bat IFNγ. Our results demonstrate that P. alecto IFNγ is conserved with IFNγ from other species and is induced in bat splenocytes following stimulation with T cell mitogens. P. alecto IFNγ has antiviral activity on Semliki forest virus in cell lines from P. alecto and the microbat, Tadarida brasiliensis. Additionally recombinant bat IFNγ was able to mitigate Hendra virus infection in P. alecto cells. These results provide the first evidence for an antiviral role for bat IFNγ in vitro in addition to the application of important immunological reagents for further studies of bat antiviral immunity.


title: Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

text: Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r(2)≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination.


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title: Call to action for improved case definition and contact tracing for MERS-CoV

text: Progress has been made in KSA in reducing the number and size of healthcare facilities outbreaks of MERS-CoV by the application of wide scope case definition leading to excessive MERS-CoV testing. Critical case definition review and application of point of care testing with revision of HCWs furlough are urgently needed.


title: Enteroviruses, type 1 diabetes and hygiene: a complex relationship

text: Type 1 diabetes (T1D) is an autoimmune disease in which the immune system mounts an attack on the host's insulin‐producing β cells. Because most cases of T1D cannot be attributed only to individual genetics, it is strongly inferred that there is a significant environmental contribution, such as infection, impacting disease development. The human enteroviruses (HEV) are common picornaviruses often implicated as triggers of human T1D, although precisely which of the numerous HEV may be involved in human T1D development is unknown. Experiments using non‐obese diabetic (NOD) mice, commonly used to model T1D, show that induction of T1D by HEV infection in NOD mice is a multifactorial process involving both the virus and the host. Interestingly, results demonstrate that HEV infection of NOD mice can also induce long‐term protection from T1D under certain conditions, suggesting that a similar mechanism may occur in humans. Based upon both experimental animal and observational human studies, we postulate that HEV have a dual role in T1D development and can either cause or prevent autoimmune disease. Whichever outcome occurs depends upon multiple variables in the host‐virus equation, many of which can be deduced from results obtained from NOD mouse studies. We propose that the background to the sharply rising T1D incidences observed in the 20th century correlates with increased levels of hygiene in human societies. Viewing T1D in this perspective suggests that potential preventative options could be developed. Copyright © 2009 John Wiley & Sons, Ltd.


title: “Off-label” use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers

text: Summary Introduction: COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences. Methods: Since March 27th, 2020, the French Pharmacovigilance Network directed all cardiac adverse drug reactions associated with “off-label” use of hydroxychloroquine, azithromycin and lopinavir-ritonavir in COVID-19 to the Nice Regional Center of Pharmacovigilance. Each Regional Center of Pharmacovigilance first assessed causality of drugs. We performed a specific analysis of these cardiac adverse drug reactions amidst an array of risk factors, reassessed the electrocardiograms and estimated their incidence in coronavirus-disease-2019. Results: In one month, 120 reports of cardiac adverse drug reactions have been notified, 102 of which associated with hydroxychloroquine alone (85%), or associated with azithromycin (60%). Their estimated incidence is 0.77% to 1.54% of all patients, notwithstanding strong underreporting. Lopinavir-ritonavir came third with 17 reports (14%) and chloroquine fourth with 3 reports (2.5%). There were 8 sudden, unexplained or aborted deaths (7%), 8 ventricular arrhythmias (7 %), 90 reports of prolonged QTc (75%) most of them “serious” (64%), 48 of which proved ≥ 500 ms, 20 reports of severe conduction disorders (17%) and 5 reports of other cardiac causes (4%). Six reports derived from automedication. Discussion and conclusion: “Off-label” use of treatments in COVID-19 increases the risk of cardiac ADRs, some of them avoidable. Even if these drugs are perceived as familiar, they are used in patients with added risk factors caused by infection. Precautions should be taken to mitigate the risk, even if they will be proven efficacious.


title: Analysis of toxic effluents released from PVC carpet under different fire conditions

text: Abstract A large number of investigations have been reported on minimising the PAH and PCDD/F yields during controlled combustion, such as incineration. This study is an attempt to quantify acute and chronic toxicants including PAH and PCDD/F in conditions relating to unwanted fires. This paper investigates distribution patterns of fire effluents between gas and aerosol phase, and the different particle size-ranges produced under different fire conditions. PVC carpet was selected as the fuel as a precursor for both PAH and PCDD/F. In order to generate fire effluents under controlled fire conditions, the steady-state tube furnace, was chosen as the physical fire model. Fire scenarios included oxidative pyrolysis, well-ventilated and under-ventilated fires. Fire effluent measurements included: carbon monoxide, carbon dioxide, hydrogen chloride, polycyclic aromatic hydrocarbons, chlorinated dibenzo-dioxins and furans and soot. The distribution patterns between gas and particle phase, and the size-ranges of the particles produced in these fires together with their chemical composition is also reported. Significant quantities of respirable submicron particles were detected, together with a range of PAHs. Lower levels of halogenated dioxins were detected in the fire residue compared with those found in other studies. Nevertheless, the findings do have implications for the health and safety of fire and rescue personnel, fire investigators, and other individuals exposed to the residue from unwanted fires.


title: Drug hypersensitivity causing organizing eosinophilic pneumonia in a pediatric patient

text: Abstract Objective To describe a relatively rare hypersentivity reaction with pulmonary manifestations in a pediatric patient. Data sources Electronic medical records. Study selection Patient treatment in the pediatric critical care unit. Data extraction and synthesis Electronic medical records. Conclusions Eosinophilic pneumonias are rare in the pediatric population. Peripheral eosinophilia is not necessary to make the diagnosis. Bronchoalveolar lavage is the diagnostic study of choice. Lung biopsies are rarely needed to make the diagnosis. The treatment of choice is steroids. If steroids fail to improve the patient's condition, consider IVIG, and cyclosporine A.


title: Biochemical principles and inhibitors to interfere with viral capping pathways

text: Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases (‘cap-snatching’). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors. Thus, it is now admitted that capping enzymes are validated antiviral targets, as their inhibition will support an antiviral response in addition to the attenuation of viral mRNA translation. In this review, we describe the different viral enzymes involved in mRNA capping together with relevant inhibitors, and their biochemical features useful in inhibitor discovery.


title: The current state of cardiology in China

text: Abstract Cardiology in China has shown significant changes in the last decade or so. Interventional cardiology, in particular, has shown remarkable advances, especially in the management of coronary artery disease, which, unfortunately, has shown a disconcerting increase in incidence in a country traditionally known for very low incidence of coronary artery disease. Important contributing factors include increasing affluence, westernization of dietary habit and lifestyle, and rampant cigarette smoking. At present, the Chinese population has an annual coronary mortality of one sixth of that reported in the West, an incidence of acute myocardial infarction of one tenth to one eighth, and a mortality of acute myocardial infarction of one eighth. The prevalence of coronary artery disease among the general Chinese population (3–7%) is roughly one quarter of that among the Caucasians in the West, but this will get worse for sure. China still has a lot of catching up to do to reach full modernization. There is a price that every developing country must pay for modernization. However, let the price the Chinese pay not exceed the benefits derived from modernization. Can we achieve a utopian stage in the 21st century in which the modern Chinese retain their ancestral low rates of coronary artery disease while adapting the positive aspects of a modern western lifestyle?


The National Children’s Study: A Critical National Investment


title: Detection of a new bat gammaherpesvirus in the Philippines

text: A new bat herpesvirus was detected in the spleen of an insectivorous bat (Hipposideros diadema, family Hipposideridae) collected on Panay Island, the Philippines. PCR analyses were performed using COnsensus-DEgenerate Hybrid Oligonucleotide Primers (CODEHOPs) targeting the herpesvirus DNA polymerase (DPOL) gene. Although we obtained PCR products with CODEHOPs, direct sequencing using the primers was not possible because of high degree of degeneracy. Direct sequencing technology developed in our rapid determination system of viral RNA sequences (RDV) was applied in this study, and a partial DPOL nucleotide sequence was determined. In addition, a partial gB gene nucleotide sequence was also determined using the same strategy. We connected the partial gB and DPOL sequences with long-distance PCR, and a 3741-bp nucleotide fragment, including the 3′ part of the gB gene and the 5′ part of the DPOL gene, was finally determined. Phylogenetic analysis showed that the sequence was novel and most similar to those of the subfamily Gammaherpesvirinae.


docid: vskcnvua

title: Thrombotic occlusive vasculopathy in skin biopsy from a livedoid lesion of a COVID‐19 patient

text: Some authors have reported the presence of cutaneous lesions related to new COronaVirus Disease 2019 (CoViD‐19) caused by SARS‐CoV‐2, in up to 20.4% of the cases; however, these lesions are not well characterized either clinically or histopathologically.(1) Recently, it has been highlighted the finding of congested and edematous blood vessels in the alveolar septum along with hyaline thrombi, and also in the heart, liver and kidney of autopsies of 3 patients deceased due to severe infection by SARS‐CoV‐2.


docid: zbmzjsvs

title: Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China

text: BACKGROUND: Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. METHODS: One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. RESULTS: Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (<26 μmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. CONCLUSION: AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.


title: Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum

text: The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.


title: Rapid Modification of Workflows and Fellow Staffing at a Single Transplant Center to Address the COVID-19 Crisis

text: Abstract Background Although hospital systems have largely halted elective surgical practices in preparing their response to the SARS-CoV-2 pandemic, transplantation remains an essential and lifesaving surgical practice. In order to continue transplantation while protecting immunocompromised patients and healthcare workers, significant restructuring of normal patient care practice habits is required. Methods This is a non-randomized, descriptive study of the abdominal transplant program at one academic center (University of California, San Francisco) and the programmatic changes undertaken to safely continue transplantations. Patient transfers, fellow utilization, and patient discharge education were identified as key areas requiring significant reorganization. Results The University of California, San Francisco abdominal transplant program took an early and aggressive approach to restructuring inpatient workflows and healthcare worker staffing. We formalized a COVID-19 transfer system to address patients in need of services at our institution while minimizing the risk of SARS-CoV-2 on our transplant ward and utilized technological approaches to provide virtual telehealth where possible, We also modified our transplant fellow staffing and responsibilities to develop an adequate backup system in the case of potential exposures. Conclusion Every transplant program is unique, and an individualized plan to adapt and modify standard clinical practices will be required to continue providing essential transplantation services. Our experience highlights areas of attention specific to transplant programs, and may provide generalizable solutions to support continued transplantation in the COVID-19 era.


Confronting the New Challenge in Travel Medicine: SARS


title: Operational issues and network effects in vaccine markets

text: One of the most important concerns for managing public health is the prevention of infectious diseases. Although vaccines provide the most effective means for preventing infectious diseases, there are two main reasons why it is often difficult to reach a socially optimal level of vaccine coverage: (i) the emergence of operational issues (such as yield uncertainty) on the supply side, and (ii) the existence of negative network effects on the consumption side. In particular, uncertainties about production yield and vaccine imperfections often make manufacturing some vaccines a risky process and may lead the manufacturer to produce below the socially optimal level. At the same time, negative network effects provide incentives to potential consumers to free ride off the immunity of the vaccinated population. In this research, we consider how a central policy-maker can induce a socially optimal vaccine coverage through the use of incentives to both consumers and the vaccine manufacturer. We consider a monopoly market for an imperfect vaccine; we show that a fixed two-part subsidy is unable to coordinate the market, but derive a two-part menu of subsidies that leads to a socially efficient level of coverage.


title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.


title: Community-acquired adenovirus pneumonia in a patient with chronic lymphatic leukaemia

text: Described here is a severe case of community-acquired adenovirus pneumonia that occurred in a previously healthy 54-year-old male who was later determined to have stage A chronic lymphatic leukemia. The clinical presentation was consistent with that of atypical pneumonia. Testing with PCR revealed adenovirus in a bronchoalveolar lavage sample, while all other tests to determine a bacterial or virological etiology were negative. Further examination of the patient revealed the previously undiagnosed chronic lymphatic leukemia. Following treatment with human immunoglobulin and oxygen therapy with continuous positive airway pressure support the patient recovered from the pneumonia completely.


docid: nyyunoha

title: An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system

text: A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components. The synthetic WNV, produced by transfection of in vitro transcribed RNA into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus. No differences were found concerning viral growth in mammalian and insect cell lines and concerning expression of viral proteins in cells. There were also no significant differences in virulence in mice following intranasal challenge. After immunizations of mice with experimental vaccines derived from the synthetic and wild-type viruses, protection from lethal challenge was achieved with similar amounts of antigen. Both vaccine preparations also induced comparable levels of neutralizing antibodies in mice. In addition, the synthetic approach turned out to be very accurate, since the rescued WNV genome contained no undesired mutations. Thus, the first flavivirus based on chemical gene synthesis was indistinguishable from the parent virus. This demonstrates that virus isolates from animal sources are dispensable to derive seed viruses for vaccine production or research.