title: Epidemiology of community-acquired respiratory tract infections in adults Incidence, etiology, and impact

text: Abstract Upper respiratory tract infections are the most common types of infectious diseases among adults. It is estimated that each adult in the United States experiences two to four respiratory infections annually. The morbidity of these infections is measured by an estimated 75 million physician visits per year, almost 150 million days lost from work, and more than $10 billion In costs for medical care. Serotypes of the rhinoviruses account for 20 to 30 percent of episodes of the common cold. However, the specific causes of most upper respiratory infections are undefined. Pneumonia remains an important cause of morbidity and mortality for nonhospitalized adults despite the widespread use of effective antimicrobial agents. There are no accurate figures on the number of episodes of pneumonia that occur each year in ambulatory patients. In younger adults, the atypical pneumonia syndrome Is the most common clinical presentation; Mycoplasma pneumoniae is the most frequently Identified causative agent. Other less common agents include Legionelia pneumophila, influenza viruses, adenoviruses, and Chiamydia. More than half a million adults are hospitalized each year with pneumonia. Persons older than 65 years of age have the highest rate of pneumonia admissions, 11.5 per 1,000 population. Pneumonia ranks as the sixth leading cause of death in the United States. The pathogens responsible for community-acquired pneumonlas are changing. Forty years ago, Streptococcus pneumoniae accounted for the majority of infections. Today, a broad array of community-acquired pathogens have been implicated as etiologic agents Including Leglonella species, gram-negative bacilli, Hemophilus influenzae, Staphylococcus aureus and nonbacterial pathogens. Given the diversity of pathogenic agents, it has become imperative for clinicians to establish a specific etiologic diagnosis before initiating therapy or to consider the diagnostic possibilities and treat with antimicrobial agents that are effective against the most likely pathogens.


title: Coronavirus infection of spotted hyenas in the Serengeti ecosystem

text: Abstract Sera from 38 free-ranging spotted hyenas (Crocuta crocuta) in the Serengeti ecosystem, Tanzania, were screened for exposure to coronavirus of antigenic group 1. An immunofluorescence assay indicated high levels of exposure to coronavirus among Serengeti hyenas: 95% when considering sera with titer levels of ≥1:10 and 74% when considering sera with titer levels of ≥1:40. Cubs had generally lower mean titer levels than adults. Exposure among Serengeti hyenas to coronavirus was also confirmed by a serum neutralisation assay and an ELISA. Application of RT-PCR to 27 fecal samples revealed viral RNA in three samples (11%). All three positive fecal samples were from the 15 juvenile animals (<24 months of age) sampled, and none from the 12 adults sampled. No viral RNA was detected in tissue samples (lymph node, intestine, lung) from 11 individuals. Sequencing of two amplified products from the S protein gene of a positive sample revealed the presence of coronavirus specific RNA with a sequence homology to canine coronavirus of 76 and 78% and to feline coronavirus type II of 80 and 84%, respectively. Estimation of the phylogenetic relationship among coronavirus isolates indicated considerable divergence of the hyena variant from those in European, American and Japanese domestic cats and dogs. From long-term observations of several hundred known individuals, the only clinical sign in hyenas consistent with those described for coronavirus infections in dogs and cats was diarrhea. There was no evidence that coronavirus infection in hyenas caused clinical signs similar to feline infectious peritonitis in domestic cats or was a direct cause of mortality in hyenas. To our knowledge, this is the first report of coronavirus infection in Hyaenidae.


title: Immunity and protection from COVID‐19—Environmental mycobacteria play a role

text: Kerboua et al1 discussed about the immunity induced by nonspecific inflammation and BCG (Bacillus Calmette-Guerin) as factors altering the susceptibility to severe illness from coronavirus disease 2019 (COVID-19). Ozdemir et al2 in their study have shown proportionately less number of cases, milder illness and a lower death rate in BCG vaccinated population as compared to BCG non-vaccinated across different countries and hemispheres.2 This article is protected by copyright. All rights reserved.


title: SARS: radiological features

text: Air‐space disease is typical in severe acute respiratory syndrome (SARS) and may be indistinguishable from pneumonia of other causes. In the majority of patients, ground glass opacities on chest radiographs progress rapidly to focal, multifocal or diffuse consolidation. Unilateral involvement is common in the early acute phase, becoming bilateral at maximal lung involvement. Generally, radiographic opacities peak between 8 and 10 days after onset of illness, with radiographic scores reflecting temporal changes in clinical and laboratory parameters such as oxygen saturation (SaO(2)) and liver transaminases. Pleural effusions, cavitating consolidation and mediastinal lymphadenopathy are not typical radiographic features. Pneumomediastinum and pneumothoraces are complications that are associated with extensive disease, with or without assisted ventilation. The utility of high resolution computed tomography (HRCT) and CT scans lies in the confirmation of airspace opacities in cases with normal initial chest radiographs that have strong contact history and signs and symptoms highly suspicious of SARS during the outbreak, allowing early treatment and prompt isolation. The characteristic HRCT feature in the acute phase is ground‐glass opacities with smooth interlobular septal thickening, sometimes with consolidation in a subpleural location, which progress rapidly to involve other areas of the lungs. Temporal lung changes documented on HRCT suggest that some residual opacities found may not be reversible.


title: Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015

text: Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). Two false negative RT-PCR on upper respiratory tract samples on days 2 and 3 led to a 48-hour diagnosis delay and a decision to transfer the patient out of the negative pressure unit (NPU). Subsequent examination of sputum later on day 3 confirmed MERS coronavirus (MERS-CoV) infection. The patient was immediately moved back into the NPU and then transferred to Bamrasnaradura Infectious Disease Institute. Over 170 contacts were traced; 48 were quarantined and 122 self-monitored for symptoms. High-risk close contacts exhibiting no symptoms, and whose laboratory testing on the 12th day after exposure was negative, were released on the 14th day. The Omani Ministry of Health (MOH) was immediately notified using the International Health Regulation (IHR) mechanism. Outbreak investigation was conducted in Oman, and was both published on the World Health Organization (WHO) intranet and shared with Thailand’s IHR focal point. The key to successful infection control, with no secondary transmission, were the collaborative efforts among hospitals, laboratories and MOHs of both countries.


title: Cross-sectional study of MERS-CoV-specific RNA and antibodies in animals that have had contact with MERS patients in Saudi Arabia

text: Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged coronavirus that is associated with a severe respiratory disease in humans in the Middle East. The epidemiological profiles of the MERS-CoV infections suggest zoonotic transmission from an animal reservoir to humans. Methods This study was designed to investigate animal herds associated with Middle East respiratory syndrome (MERS)-infected patients in Saudi Arabia, during the last three years (2014–2016). Nasal swabs and serum samples from 584 dromedary camels, 39 sheep, 51 goats, and 2 cattle were collected. Nasal samples from camels, sheep, goats, and cattle were examined by real-time reverse-transcription PCR (RT-PCR) to detect MERS-CoV RNA, and the Anti-MERS ELISA assay was performed to detect camel humeral immune response (IgG) to MERS-CoV S1 antigen infection. The complete genome sequencing of ten MERS-CoV camel isolates and phylogenetic analysis was performed. Results The data indicated that seventy-five dromedary camels were positive for MERS-CoV RNA; the virus was not detected in sheep, goats, and cattle. MERS-CoV RNA from infected camels was not detected beyond 2 weeks after the first positive result was detected in nasal swabs obtained from infected camels. Anti-MERS ELISA assays showed that 70.9% of camels related to human cases had antibodies to MERS-CoV. The full genome sequences of the ten MERS-CoV camel isolates were identical to their corresponding patients and were grouped together within the larger MERS-CoV sequences cluster for human and camel isolates reported form the Arabian Peninsula. Conclusions These findings indicate that camels are a significant reservoir for the maintenance of MERS-CoVs, and they are an important source of human infection with MERS.


title: Examining Landscape Factors Influencing Relative Distribution of Mosquito Genera and Frequency of Virus Infection

text: Mosquito-borne infections cause some of the most debilitating human diseases, including yellow fever and malaria, yet we lack an understanding of how disease risk scales with human-driven habitat changes. We present an approach to study variation in mosquito distribution and concomitant viral infections on the landscape level. In a pilot study we analyzed mosquito distribution along a 10-km transect of a West African rainforest area, which included primary forest, secondary forest, plantations, and human settlements. Variation was observed in the abundance of Anopheles, Aedes, Culex, and Uranotaenia mosquitoes between the different habitat types. Screening of trapped mosquitoes from the different habitats led to the isolation of five uncharacterized viruses of the families Bunyaviridae, Coronaviridae, Flaviviridae, and Rhabdoviridae, as well as an unclassified virus. Polymerase chain reaction screening for these five viruses in individual mosquitoes indicated a trend toward infection with specific viruses in specific mosquito genera that differed by habitat. Based on these initial analyses, we believe that further work is indicated to investigate the impact of anthropogenic landscape changes on mosquito distribution and accompanying arbovirus infection.


Is climate change the next pandemic for dermatology? Lessons from COVID‐19


Rx for survival: a global health challenge


title: Best behaviour

text: Scientists are trying to control our actions in this pandemic, but what happens when they get things wrong? Graham Lawton reports


Fungal antigenemia in patients with severe Coronavirus Disease 2019 (COVID-19): the facts and challenges


title: The novel corona virus and rhinology: Impact on practice patterns and future directions

text: OBJECTIVES: To evaluate the impact of the novel coronavirus pandemic on practice patterns, clinical behavior, personal health, and emotional/psychological concerns of rhinologists. METHODS: A 15-question survey was sent out to the American Rhinologic Society's (ARS) membership to determine the impact of COVID-19 during the crisis. Demographic factors and practice patterns were collected and evaluated. RESULTS: There were 224 total respondents out of 835 ARS members queried (26.8% response rate). Study queries were sent in April 2020. Notably, 17.8% reported illness in themselves or their staff and 74.4% noted a psychological/emotional impact. A plurality of rhinologists noted their practice volume and in-office procedure volume has become 20.0% and 0.0% of their prior volumes, respectively. In addition, 96.2% were noted to be using telemedicine in our subspecialty. CONCLUSION: In addition to severely impacting volume and the perception of future decreases in patients and revenue, the COVID-19 pandemic has had a physical and emotional impact on rhinologists in ways that need to be further studied. These data include significantly novel and objective information. The COVID-19 crisis also reveals the important role of telemedicine in rhinology. Guidelines regarding personal protective equipment for in-office visits, nasal endoscopy, and other in-office and operating room procedures would be particularly helpful as future waves are expected.


title: Nonsteroidal anti-inflammatory drug therapy for neonatal calf diarrhea complex: Effects on calf performance

text: The aim of this study was to examine the efficacy of meloxicam (MEL) as supportive therapy for calves with neonatal calf diarrhea complex. For this double-blind controlled trial, 62 Holstein male calves were purchased at birth and transported to a research facility. At the naturally occurring onset of diarrhea, defined as the first occurrence of a fecal score greater than 2 on a 4-point scale, calves were enrolled in the study. Each calf with diarrhea was randomly assigned to receive a single subcutaneous injection of MEL at a rate of 0.5 mg/kg of BW or an equal volume of placebo (PLA) solution. Milk, starter ration, and water intakes were determined daily for each calf from arrival until 56 d of age. The calves were weighed on arrival and each week thereafter. Time to weaning and weaning weight were recorded for each calf. Crude associations between treatment and each outcome variable were examined using t-tests and Pearson chi-squared tests. Subsequently, multivariable regression models were constructed to examine the impact of MEL therapy on meaningful outcome variables. The primary experimental unit in all analyses was the individual calf. In total, 56 calves presented with clinical signs of diarrhea and were enrolled in the study. Two PLA-treated calves died after being enrolled in the study, and there was no calf mortality among the MEL-treated calves. For calves that developed diarrhea after 10 d of age, MEL-treated calves were more likely to consume their entire daily milk allowance (P < 0.05) as compared with PLA-treated calves. Meloxicam-treated calves began consuming starter ration earlier (P < 0.01) and at a greater rate (P < 0.001), and consumed more water (P < 0.001) compared with PLA-treated animals. Over the study period, calves treated with MEL gained BW at a faster rate (P < 0.01) than calves treated with PLA. There was no difference in weaning weight (P > 0.05), but MEL-treated calves tended to wean earlier (P = 0.11) than PLA-treated calves. These results demonstrate that calves receiving a single injection of MEL at the onset of diarrhea had improved appetite and performance compared with PLA-treated calves. Thus, MEL is an effective supportive therapy for neonatal calf diarrhea complex.


Identification and management of asymptomatic carriers of coronavirus disease 2019 (COVID‐19) in China


title: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan

text: INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.


Vinblastine-induced Acral Hyperpigmentation


title: Complete Genome Sequence of Porcine Sapelovirus Strain USA/IA33375/2015 Identified in the United States

text: The complete genome of sapelovirus A, formerly known as porcine sapelovirus (PSV), from a diarrheic pig was sequenced for the first time in the United States (designated PSV USA/IA33375/2015). It shares 87.8% to 83.9% nucleotide identities with other reported PSV strains globally and is most closely related to Asia PSV strains.


title: Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study

text: BACKGROUND: COVID-19 is an ongoing global pandemic. Changes in haematological characteristics in patients with COVID-19 are emerging as important features of the disease. We aimed to explore the haematological characteristics and related risk factors in patients with COVID-19. METHODS: This retrospective cohort study included patients with COVID-19 admitted to three designated sites of Wuhan Union Hospital (Wuhan, China). Demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records and compared between patients with moderate, severe, and critical disease (defined according to the diagnosis and treatment protocol for novel coronavirus pneumonia, trial version 7, published by the National Health Commission of China). We assessed the risk factors associated with critical illness and poor prognosis. Dynamic haematological and coagulation parameters were investigated with a linear mixed model, and coagulopathy screening with sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scoring systems was applied. FINDINGS: Of 466 patients admitted to hospital from Jan 23 to Feb 23, 2020, 380 patients with COVID-19 were included in our study. The incidence of thrombocytopenia (platelet count <100 × 10(9) cells per L) in patients with critical disease (42 [49%] of 86) was significantly higher than in those with severe (20 [14%] of 145) or moderate (nine [6%] of 149) disease (p<0·0001). The numbers of lymphocytes and eosinophils were significantly lower in patients with critical disease than those with severe or moderate disease (p<0·0001), and prothrombin time, D-dimer, and fibrin degradation products significantly increased with increasing disease severity (p<0·0001). In multivariate analyses, death was associated with increased neutrophil to lymphocyte ratio (≥9·13; odds ratio [OR] 5·39 [95% CI 1·70–17·13], p=0·0042), thrombocytopenia (platelet count <100 × 10(9) per L; OR 8·33 [2·56–27·15], p=0·00045), prolonged prothrombin time (>16 s; OR 4·94 [1·50–16·25], p=0·0094), and increased D-dimer (>2 mg/L; OR 4·41 [1·06–18·30], p=0·041). Thrombotic and haemorrhagic events were common complications in patients who died (19 [35%] of 55). Sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scores (assessed in 12 patients who survived and eight patients who died) increased over time in patients who died. The onset of sepsis-induced coagulopathy was typically before overt disseminated intravascular coagulation. INTERPRETATION: Rapid blood tests, including platelet count, prothrombin time, D-dimer, and neutrophil to lymphocyte ratio can help clinicians to assess severity and prognosis of patients with COVID-19. The sepsis-induced coagulopathy scoring system can be used for early assessment and management of patients with critical disease. FUNDING: National Key Research and Development Program of China.


title: Using Gaussian model to improve biological sequence comparison

text: One of the major tasks in biological sequence analysis is to compare biological sequences, which could serve as evidence of structural and functional conservation, as well as of evolutionary relations among the sequences. Numerous efficient methods have been developed for sequence comparison, but challenges remain. In this article, we proposed a novel method to compare biological sequences based on Gaussian model. Instead of comparing the frequencies of k‐words in biological sequences directly, we considered the k‐word frequency distribution under Gaussian model which gives the different expression levels of k‐words. The proposed method was tested by similarity search, evaluation on functionally related genes, and phylogenetic analysis. The performance of our method was further compared with alignment‐based and alignment‐free methods. The results demonstrate that Gaussian model provides more information about k‐word frequencies and improves the efficiency of sequence comparison. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010


title: The Blood of Christ Compels Them: State Religiosity and State Population Mobility During the Coronavirus (COVID-19) Pandemic

text: This paper examines the association between state religiosity and population mobility during the coronavirus (COVID-19) pandemic. We use first-party geo-behavioral data collected through mobile phone operating systems, global positioning systems, and Wi-Fi signals to assess changes in the average median distance traveled by approximately 15,000,000 devices over eight weeks (February 24–April 13) in the contiguous United States. Robust regression results show that more religious states tend to exhibit higher average mobility scores and slower average declines in mobility. Findings also suggest that state stay-at-home orders have a weaker impact on mobility in more religious states.


title: Nasal swab samples and real-time polymerase chain reaction assays in community-based, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control

text: BACKGROUND: Carefully conducted, community-based, longitudinal studies are required to gain further understanding of the nature and timing of respiratory viruses causing infections in the population. However, such studies pose unique challenges for field specimen collection, including as we have observed the appearance of mould in some nasal swab specimens. We therefore investigated the impact of sample collection quality and the presence of visible mould in samples upon respiratory virus detection by real-time polymerase chain reaction (PCR) assays. METHODS: Anterior nasal swab samples were collected from infants participating in an ongoing community-based, longitudinal, dynamic birth cohort study. The samples were first collected from each infant shortly after birth and weekly thereafter. They were then mailed to the laboratory where they were catalogued, stored at -80°C and later screened by PCR for 17 respiratory viruses. The quality of specimen collection was assessed by screening for human deoxyribonucleic acid (DNA) using endogenous retrovirus 3 (ERV3). The impact of ERV3 load upon respiratory virus detection and the impact of visible mould observed in a subset of swabs reaching the laboratory upon both ERV3 loads and respiratory virus detection was determined. RESULTS: In total, 4933 nasal swabs were received in the laboratory. ERV3 load in nasal swabs was associated with respiratory virus detection. Reduced respiratory virus detection (odds ratio 0.35; 95% confidence interval 0.27-0.44) was observed in samples where the ERV3 could not be identified. Mould was associated with increased time of samples reaching the laboratory and reduced ERV3 loads and respiratory virus detection. CONCLUSION: Suboptimal sample collection and high levels of visible mould can impact negatively upon sample quality. Quality control measures, including monitoring human DNA loads using ERV3 as a marker for epithelial cell components in samples should be undertaken to optimize the validity of real-time PCR results for respiratory virus investigations in community-based studies.


title: Development of a murine model to study the pathogenesis of rotavirus infection

text: Abstract A murine model to study enteritis induced by bovine (BRV) and murine rotavirus (MRV) has been developed. The course of infection was determined by clinical symptoms of diarrhea and virus isolation as well as histopathological, immunohistochemical, and electron microscopic methods. Both isolates were able to replicate and produce clinical symptoms in neonatal mice. Rotavirus-free neonates were orally inoculated with MRV or BRV and observed over a 192-hr postinoculation (HPI) period. Following infection with 104 PFU of virus, diarrhea and maximal intestinal dysfunction, as measured by xylose absorption, did not occur until beyond 20 hr postinfection even though maximal virus production occurred at 10–15 HPI. Immunohistochemically and by electron microscopy we were able to demonstrate viral antigen and virus particles in the enterocytes of villous tips at 5–8 HPI. The appearance of diarrheal symptoms was dependent on the virus dose and the type of virus isolate inoculated. The disease could be induced with doses as low as 1 × 102 PFU/mouse of BRV and 1 × 101 PFU/mouse of MRV. On the basis of these results, MRV was found to be more virulent than BRV in this model. The model should prove useful for studies designed to assess rotavirus virulence genes and for vaccine protection studies. This work emphasizes the need for early sample collection for critical evaluation of any vaccine or antiviral agent using this model.


NTD policy priorities: Science, values, and agenda setting


title: Isolation and pathogenicity of the mammalian orthoreovirus MPC/04 from masked civet cats

text: Abstract Mammalian reoviruses (MRVs) are associated with pulmonary infections and have been isolated from humans and various animals experiencing respiratory illness. We report here the first case of an MRV detected in the masked palm civet, which showed the highest similarity to the serotype 3 MRV. Reovirus particles were identified by electron microscopic examination of both negative-stain and thin-section. Genomic pattern analysis on SDS-PAGE showed that MPC/04 had 10-segmented double-strand RNA genome. Intranasal infection of four-week-old female BALB/c mice resulted in fatal respiratory distress but not other routes. Infections caused tissue damage and inflammation. MPC/04 grew to higher titers in the lungs than in other tissues. This research strongly suggests a need for additional experimentation to understand the pathogenic mechanisms of mammalian orthoreoviruses in infected animals and humans.


title: Antiviral effect of lithium chloride on porcine epidemic diarrhea virus in vitro

text: Abstract Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. Severe outbreaks of PEDV variants have re-emerged in Asia and North America since 2010, causing tremendous economic losses to the swine industry. The lack of effective therapeutic treatment promotes the research for new antivirals. Lithium chloride (LiCl) has been reported as a potential antiviral drug for certain viruses. In this study, the antiviral effect of LiCl on PEDV in Vero cells was evaluated. Real-time quantitative PCR and indirect immunofluorescence assay indicated that LiCl effectively inhibited the entry and replication of PEDV in Vero cells. The expression of viral RNA and protein of PEDV in Vero cells was suppressed in a dose-dependent manner by LiCl. Moreover, addition of LiCl inhibited both early and late cell apoptosis induced by PEDV. Our data implied that LiCl could be a potential antiviral drug against PEDV infection. Further studies are required to explore the antiviral effect of lithium chloride on PEDV infection in vivo.


title: More bark than bite: Comparative studies are needed to determine the importance of canine zoonoses in Aboriginal communities. A critical review of published research

text: The objective of this review was to identify and critique over forty years of peer‐reviewed literature concerned with the transmission of canine zoonoses to Aboriginal people and determine the zoonotic organisms documented in dogs in Australian Aboriginal communities. A systematic literature search of public health, medical and veterinary databases identified 19 articles suitable for critical appraisal. Thirteen articles documented the occurrence of recognized zoonotic organisms in dogs in Aboriginal communities, including Toxocara canis, Dirofilaria immitis, Streptococcus dysgalactiae, Rickettsia felis, Sarcoptes scabiei and Giardia. Currently, there is definitive evidence indicating that dogs act as a reservoir for human scabies in Aboriginal communities. However, there is a need for large‐scale, high‐quality, comparative studies of dogs and humans from the same household to assess the occurrence and importance of transmission of S. scabiei and other diseases between dogs and humans. These studies should use current genetic and molecular techniques along with traditional techniques to identify and type organisms in order to better understand their epidemiology. This review has revealed that there is a lack of high‐quality comparative studies to determine whether dogs are contributing to human disease by transmitting zoonoses. Our recommendations differ significantly from current public health policy and may have substantial implications for human and dog health.


Editorial: Coronaviruses: Facts, Myths and Hypotheses.


title: A single-cell atlas of the peripheral immune response to severe COVID-19

text: There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.


Teicoplanin therapy leading to a significant decrease in viral load in a patient with chronic hepatitis C


title: Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus

text: Coronaviruses (CoV) are enveloped positive‐strand RNA viruses that induce different membrane rearrangements in infected cells in order to efficiently replicate and assemble. The origin, the protein composition and the function of these structures are not well established. To shed further light on these structures, we have performed a time‐course experiment in which the mouse hepatitis virus (MHV)‐induced membrane rearrangements were examined qualitatively and quantitatively by (immuno)‐electron microscopy. With our approach we were able to confirm the appearance of 6, previously reported, membranous structures during the course of a complete infection cycle. These structures include the well‐characterized double‐membrane vesicles (DMVs), convoluted membranes (CMs) and virions but also the more enigmatic large virion‐containing vacuoles (LVCVs), tubular bodies (TBs) and cubic membrane structures (CMSs). We have characterized the LVCVs, TBs and CMSs, and found that the CoV‐induced structures appear in a strict order. By combining these data with quantitative analyses on viral RNA, protein synthesis and virion release, this study generates an integrated molecular and ultrastructural overview of CoV infection. In particular, it provides insights in the role of each CoV‐induced structure and reveals that LVCVs are ERGIC/Golgi compartments that expand to accommodate an increasing production of viral particles.


title: Formes pauci-symptomatiques du syndrome respiratoire aigu sévère (sras)

text: Résumé Introduction Une épidémie de pneumopathies atypiques est apparue en novembre 2002 dans la région Chinoise de Guangdong. Elle a ensuite été décrite sous le nom de syndrome respiratoire aigu sévère (SRAS) à partir de nouveaux foyers survenus à Hanoi et à Hong Kong en février 2003. En France, 5 cas reliés au même patient source ont été rapportés. Observation Nous rapportons l’observation d’un patient de 52 ans contact direct avec un cas probable de SRAS. À l’admission, le patient présente une hyperthermie isolée sans symptomatologie respiratoire associée à une lymphopénie et une cytolyse hépatique. La radiographie thoracique est normale. La tomodensitométrie thoracique objective l’existence d’un aspect en verre dépoli sous pleural. L’étude par PCR des prélèvements naso-pharyngés précoces (36e heure) à la recherche du coronavirus associé au SARS sera négative. La confirmation du cas sera obtenue par l’étude sérologique. Conclusions Cette observation illustre l’existence de présentations cliniques frustres du syndrome respiratoire aigu sévère. La contagiosité des formes pauci symptomatiques n’est pas connue. Des analyses sérologiques permettront de mieux les préciser. Le danger actuel d’une recrudescence saisonnière particulièrement hivernale ne peut être écarté. Dans ce contexte, l’existence et la reconnaissance des formes pauci symptomatiques pour lesquelles la contagiosité ne peut être écartée est primordiale. Summary Introduction In November 2002 an epidemic of atypical pneumonia appeared in the Chinese region of Guandong. It was subsequently given the name “Severe Acute Respiratory Syndrome” (SARS) following the occurrence of further outbreaks in Hanoi and Hong Kong in February 2003. Five cases related to the same patient source have been reported in France. Case report We report the case of a patient of 52 years who had direct contact with a probable case of SARS. On admission the patient presented with pyrexia associated with lymphopenia and liver cell necrosis but no respiratory symptoms. The chest x-ray was normal. The thoracic CT scan showed a sub pleural ground glass appearance. Early (36 hours) PCR studies of naso-pharyngeal washings were negative for the coronavirus associated with SARS. The diagnosis was confirmed serologically. Conclusions This observation demonstrates the existence of incomplete clinical presentations of SARS. The infectivity of this asymptomatic form is unknown. Serological analyses will allow better identification. The continuing danger of seasonal recurrence, particularly in the winter, cannot be ignored. In this context the recognition of probably infectious asymptomatic forms is essential.


title: Emergency and Urgent Orthopaedic Surgeries in non covid patients during the COVID 19 pandemic: Perspective from India

text: OBJECTIVES: To Evaluate the results and the protocols of our Institution for 18 Emergency and Urgent Non Covid Surgeries during the Covid 19 Pandemic METHODS: 18 patients underwent Emergency and Urgent Orthopaedic Surgeries at institution. The Protocol was Screening, Segregation, Selection, Isolation, theatre modification, and Online Follow. RESULTS: Two adverse events including, one death and one intensive care admission due to underlying morbidity were recorded. Average Hospital stay was 2.5 days with no patients becoming covid positive at follow up. CONCLUSION: Strict Surgical protocols need to be followed for surgery during the Covid19 pandemic.


title: Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.


Early Experience in the COVID-19 pandemic from a Vascular Surgery Unit in a Singapore Tertiary Hospital


title: COVID‐19 health restrictions in a transplanted Italian cohort

text: An exponential diffusion of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) prompted Italian Institutions to take extraordinary healthcare restrictive measures since 8(th) March 2020, declaring quarantine for COVID‐19 (1).


Vietnam’s response to COVID-19: Prompt and proactive actions


title: Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence

text: Coronavirus-cell entry programs involve virus-cell membrane fusions mediated by viral spike (S) proteins. Coronavirus S proteins acquire membrane fusion competence by receptor interactions, proteolysis, and acidification in endosomes. This review describes our current understanding of the S proteins, their interactions with and their responses to these entry triggers. We focus on receptors and proteases in prompting entry and highlight the type II transmembrane serine proteases (TTSPs) known to activate several virus fusion proteins. These and other proteases are essential cofactors permitting coronavirus infection, conceivably being in proximity to cell-surface receptors and thus poised to split entering spike proteins into the fragments that refold to mediate membrane fusion. The review concludes by noting how understanding of coronavirus entry informs antiviral therapies.


title: Managing Febrile Respiratory Illnesses during a Hypothetical SARS Outbreak

text: Since the World Health Organization declared the global outbreak of severe acute respiratory syndrome (SARS) contained in July 2003, new cases have periodically reemerged in Asia. This situation has placed hospitals and health officials worldwide on heightened alert. In a future outbreak, rapidly and accurately distinguishing SARS from other common febrile respiratory illnesses (FRIs) could be difficult. We constructed a decision-analysis model to identify the most efficient strategies for managing undifferentiated FRIs within a hypothetical SARS outbreak in New York City during the season of respiratory infections. If establishing reliable epidemiologic links were not possible, societal costs would exceed $2.0 billion per month. SARS testing with existing polymerase chain reaction assays would have harmful public health and economic consequences if SARS made up <0.1% of circulating FRIs. Increasing influenza vaccination rates among the general population before the onset of respiratory season would save both money and lives.


title: Diacerein: a potential multi-target therapeutic drug for COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection.


title: Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns

text: Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.


title: Actitud diagnóstica y terapéutica ante la sospecha de infección broncopulmonar aguda en pacientes inmunocompetentes

text: Resumen Las infecciones respiratorias agrupan tres entidades con indicaciones terapéuticas diferentes: la bronquitis aguda, la neumonía aguda y las exacerbaciones de la bronquitis crónica. Por consiguiente, es importante diferenciarlas. La bronquitis aguda es muy frecuente, de fácil diagnóstico y de evolución benigna. Por regla general, es de origen viral, y la antibioticoterapia no está justificada. Por el contrario, las neumonías agudas son poco frecuentes pero tienen un riesgo evolutivo de potencial gravedad y representan la sexta causa de mortalidad. Su etiología suele ser bacteriana en el adulto y siempre requieren antibioticoterapia. Su diagnóstico clínico es de presunción, basado en los siguientes signos: fiebre, taquicardia, taquipnea, dolor torácico, estertores crepitantes en el foco de infección e impresión de gravedad. Estos signos justifican la realización de una radiografía de tórax. Las exacerbaciones de la bronquitis crónica pueden ser de origen bacteriano, viral o no infeccioso. Las indicaciones de la antibioticoterapia dependerán de la probabilidad de su etiología bacteriana (aumento de volumen y aspecto purulento de la expectoración, aparición o empeoramiento de la disnea) y del estadio evolutivo de la bronquitis crónica (simple, obstructiva sin insuficiencia respiratoria crónica, insuficiencia respiratoria crónica).


title: Evidence of nosocomial transmission of human rhinovirus in a neonatal intensive care unit

text: Nosocomial respiratory infections cause significant morbidity and mortality, especially among the extremely susceptible neonatal population. Human rhinovirus C is a common viral respiratory illness that causes significant complications in children <2 years old. We describe a nosocomial outbreak of human rhinovirus C in a level II-III neonatal intensive care unit in an urban public safety net hospital.


Introduction: urgent anthropological COVID‐19 forum


title: Identification of novel ligands for the RNA pseudoknot that regulate −1 ribosomal frameshifting

text: Abstract In many viruses, −1 ribosomal frameshifting (−1RF) regulates synthesis of proteins and is crucial for virus production. An RNA pseudoknot is one of the essential components of the viral −1RF system. Thermodynamic or kinetic control of pseudoknot folding may be important in regulating the efficiency of −1RF. Thus, small molecules that interact with viral RNA pseudoknots may disrupt the −1RF system and show antiviral activity. In this study, we conducted virtual screening of a chemical database targeting the X-ray crystal structure of RNA pseudoknot complexed with biotin to identify ligands that may regulate an −1RF system containing biotin-aptamer as an RNA pseudoknot component. After docking screening of about 80,000 compounds, 58 high-ranked hits were selected and their activities were examined by in vitro and cell-based −1 frameshifting assays. Six compounds increased the efficiency of −1 frameshifting, and these are novel small molecule compounds that regulate the −1RF.


title: Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes

text: A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a “Cytokine Storm Syndrome” (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.


Empathic communication as a “Risky Strength” for Health during the COVID-19 Pandemic: the Case of Frontline Italian Healthcare Workers


title: EFFECT OF SIALODACRYOADENITIS VIRUS INFECTION ON AXONAL REGENERATION

text: The effect of sialodacryoadenitis virus (SDAV) infection on axonal regeneration and functional recovery was investigated in male Lewis rats. Animals underwent unilateral tibial nerve transection, immediate repair, and treatment with either FK506 (treated) or control vehicle (untreated). Serial walking track analyses were performed to assess functional recovery. Nerves were harvested for morphometric analysis on postoperative day 18 after an SDAV outbreak occurred that affected the 12 experimental animals. Histomorphometry and walking track data were compared against 36 historical controls. Rats infected with SDAV demonstrated severely impaired axonal regeneration and diminished functional recovery. Total fiber counts, nerve density, and percent neural tissue were all significantly reduced in infected animals (P < 0.05). Active SDAV infection severely impaired nerve regeneration and negated the positive effect of FK506 on nerve regeneration in rats. Immunosuppressive risks must be weighed carefully against the potential neuroregenerative benefits in the treatment of peripheral nerve injuries.


title: Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)–Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection

text: With >1600 documented human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) and a case fatality rate of approximately 36%, medical countermeasures are needed to prevent and limit the disease. We examined the in vivo efficacy of the human monoclonal antibody m336, which has high neutralizing activity against MERS-CoV in vitro. m336 was administered to rabbits intravenously or intranasally before infection with MERS-CoV. Prophylaxis with m336 resulted in a reduction of pulmonary viral RNA titers by 40–9000-fold, compared with an irrelevant control antibody with little to no inflammation or viral antigen detected. This protection in rabbits supports further clinical development of m336.


title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies

text: COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the respiratory tract including the lung This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6 The binding of COVID-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1b which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1b which is a mediator of lung inflammation, fever and fibrosis Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Ra receptor IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2 The suppression of IL-1b by IL-37 in inflammatory state induced by COVID-19 can have a new therapeutic effect previously unknown Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages IL-38 is also a suppressor cytokine which inhibits IL-1b and other pro-inflammatory IL-family members IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by COVID-19, providing a new relevant strategy


title: Coronaviruses in brain tissue from patients with multiple sclerosis

text: Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E and three PCR assays with primers specific for the nucleocapsid protein of human coronavirus strain OC43 were performed. Sporadic positive PCR assays were observed in both patients and controls in some of the PCR assays. However, these results were not reproducible and there was no difference in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study.


title: Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2

text: Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.


title: Modeling COVID-19 Epidemic in Heilongjiang Province, China

text: The Coronavirus Disease 2019 (COVID-19) surges worldwide. However, massive imported patients especially into Heilongjiang Province in China recently have been an alert for local COVID-19 outbreak. We collected data from January 23 to March 25 from Heilongjiang province and trained an ordinary differential equation model to fit the epidemic data. We extended the simulation using this trained model to characterize the effect of an imported ‘escaper’. We showed that an imported ‘escaper’ was responsible for the newly confirmed COVID-19 infections from Apr 9 to Apr 19 in Heilongjiang province. Stochastic simulations further showed that significantly increased local contacts among imported ‘escaper’, its epidemiologically associated cases and susceptible populations greatly contributed to the local outbreak of COVID-19. Meanwhile, we further found that the reported number of asymptomatic patients was markedly lower than model predictions implying a large asymptomatic pool which was not identified. We further forecasted the effect of implementing strong interventions immediately to impede COVID-19 outbreak for Heilongjiang province. Implementation of stronger interventions to lower mutual contacts could accelerate the complete recovery from coronavirus infections in Heilongjiang province. Collectively, our model has characterized the epidemic of COVID-19 in Heilongjiang province and implied that strongly controlled measured should be taken for infected and asymptomatic patients to minimize total infections.


Teledermatology in the Wake of COVID-19: Advantages and Challenges to Continued Care in a Time of Disarray


title: Chemokine-like factor 1 is a functional ligand for CC chemokine receptor 4 (CCR4)

text: Abstract Chemokine-like factor 1 (CKLF1) exhibits chemotactic effects on leukocytes. Its amino acid sequence shares similarity with those of TARC/CCL17 and MDC/CCL22, the cognate ligands for CCR4. The chemotactic effects of CKLF1 for CCR4-transfected cells could be desensitized by TARC/CCL17 and markedly inhibited by PTX. CKLF1 induced a calcium flux in CCR4-transfected cells and fully desensitized a subsequent response to TARC/CCL17, and TARC/CCL17 could partly desensitize the response to CKLF1. CKLF1 caused significant receptor internalization in pCCR4-EGFP transfected cells. Taken together, CKLF1 is a novel functional ligand for CCR4.


title: Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate

text: Abstract SARS main protease is essential for life cycle of SARS coronavirus and may be a key target for developing anti-SARS drugs. Recently, the enzyme expressed in Escherichia coli was characterized using a HPLC assay to monitor the formation of products from 11 peptide substrates covering the cleavage sites found in the SARS viral genome. This protease easily dissociated into inactive monomer and the deduced K d of the dimer was 100μM. In order to detect enzyme activity, the assay needed to be performed at micromolar enzyme concentration. This makes finding the tight inhibitor (nanomolar range IC50) impossible. In this study, we prepared a peptide with fluorescence quenching pair (Dabcyl and Edans) at both ends of a peptide substrate and used this fluorogenic peptide substrate to characterize SARS main protease and screen inhibitors. The fluorogenic peptide gave extremely sensitive signal upon cleavage catalyzed by the protease. Using this substrate, the protease exhibits a significantly higher activity (k cat=1.9s−1 and K m =17 μ M) compared to the previously reported parameters. Under our assay condition, the enzyme stays as an active dimer without dissociating into monomer and reveals a small K d value (15nM). This enzyme in conjunction with fluorogenic peptide substrate provides us a suitable tool for identifying potent inhibitors of SARS protease.


title: An overview on 2‐methyl‐2,4‐pentanediol in crystallization and in crystals of biological macromolecules

text: 2‐Methyl‐2,4‐pentanediol (MPD) is the most popular chemical additive used for crystallization of biological macromolecules. However, the mechanism of its action on proteins in aqueous solution is not well understood. We have carried out a systematic analysis of the conformation and environment of MPD molecules bound to proteins. We find that the majority of MPD molecules adopt their most stable conformer. They prefer to bind to hydrophobic sites with a distinct preference for leucine side chains. Most MPD binding sites involve amino‐acid residues in helical or β‐sheet structures. MPD binding to proteins is penetrative, leading to displacement of water molecules in grooves and cavities (sometimes ligand‐binding and active sites) on the protein surface. This results in a large reduction of solvent‐accessible area, which can have significant implications for protein stability. The packing of the MPD molecules by the protein is not optimal and usually some other solvent molecules are also bound along with it. Our analysis suggests that MPD is not as strong a denaturant as often suggested. It promotes stabilization of the protein by preferential hydration, which is facilitated by attachment of MPD molecules to the hydrophobic surface.


title: Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia

text: BACKGROUND: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. OBJECTIVE: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. RESULTS: The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). CONCLUSION: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases.


title: Severe acute respiratory syndrome coronavirus nucleocapsid protein confers ability to efficiently produce virus-like particles when substituted for the human immunodeficiency virus nucleocapsid domain

text: We replaced the HIV-1 nucleocapsid (NC) domain with different N-coding sequences to test SARS-CoV nucleocapsid (N) self-interaction capacity, and determined the capabilities of each chimera to direct virus-like particle (VLP) assembly. Analysis results indicate that the replacement of NC with the carboxyl-terminal half of the SARS-CoV N resulted in the production of wild type (wt)-level virus-like particles (VLPs) with the density of a wt HIV-1 particle. When co-expressed with SARS-CoV N, chimeras containing the N carboxyl-terminal half sequence efficiently packaged N. However, the same was not true for the chimera bearing the N amino-terminal half sequence, despite its production of substantial amounts of VLPs. According to further analysis, HIV-1 NC replacement with N residues 2–213, 215–421, or 234–421 resulted in efficient VLP production at levels comparable to that of wt HIV-1, but replacement with residues 215–359, 302–421, 2–168, or 2–86 failed to restore VLP production to wild-type levels. The results suggest that the domain conferring the ability to direct VLP assembly and release in SARS-CoV N is largely contained between residues 168 and 421.


title: Therapeutic or detrimental mobilities? Walking groups for older adults

text: Abstract The health benefits of walking through greenspace have earned widespread academic attention in recent years and have been termed ‘therapeutic mobilities’. As a result, walking groups are actively encouraged by health professionals as a way to promote ‘healthy ageing’. This paper examines whether the promotion of community-led walking groups relies upon overly optimistic understandings that portray walking in greenspace as an inherently therapeutic practice. Accordingly, this paper introduces the concept of ‘detrimental mobilities’ to explore how the shared movement promoted via walking groups may not always be inherently therapeutic and may have some detrimental impacts on the individuals who take part in these activities. Drawing on findings from in-depth walking interviews with older members of the ‘Walking for Health’ scheme in Southampton, England, this paper examines how mobilities have the potential to disable, as much as they enable, health and wellbeing.


title: Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

text: The pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.


title: In-silico investigation of phytochemicals from Asparagus racemosus as plausible antiviral agent in COVID-19

text: COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high. The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus HIGHLIGHTS: Asparagus racemosus have antiviral potential. Phytochemicals of Shatavari showed promising in-silico docking and MD results. Asparaoside-C and Asparoside-F has good binding with target proteins. Asparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor . Communicated by Ramaswamy H. Sarma


title: Identification of Sumoylated Proteins in the Silkworm Bombyx mori

text: Small ubiquitin-like modifier (SUMO) modification (SUMOylation) is an important and widely used reversible modification system in eukaryotic cells. It regulates various cell processes, including protein targeting, transcriptional regulation, signal transduction, and cell division. To understand its role in the model lepidoptera insect Bombyx mori, a recombinant baculovirus was constructed to express an enhanced green fluorescent protein (eGFP)-SUMO fusion protein along with ubiquitin carrier protein 9 of Bombyx mori (BmUBC9). SUMOylation substrates from Bombyx mori cells infected with this baculovirus were isolated by immunoprecipitation and identified by LC–ESI-MS/MS. A total of 68 candidate SUMOylated proteins were identified, of which 59 proteins were functionally categorized to gene ontology (GO) terms. Analysis of kyoto encyclopedia of genes and genomes (KEGG) pathways showed that 46 of the identified proteins were involved in 76 pathways that mainly play a role in metabolism, spliceosome and ribosome functions, and in RNA transport. Furthermore, SUMOylation of four candidates (polyubiquitin-C-like isoform X1, 3-hydroxyacyl-CoA dehydrogenase, cyclin-related protein FAM58A-like and GTP-binding nuclear protein Ran) were verified by co-immunoprecipitation in Drosophila schneide 2 cells. In addition, 74% of the identified proteins were predicted to have at least one SUMOylation site. The data presented here shed light on the crucial process of protein sumoylation in Bombyx mori.


Training on the care of patients with respiratory syndrome of middle east-coronavirus and ebola virus based on clinical simulation


title: Detection of novel astroviruses in urban brown rats and previously known astroviruses in humans

text: Several novel astroviruses have been recently discovered in humans and in other animals. Here, we report results from our surveillance of astroviruses in human and rodent faecal samples in Hong Kong. Classical human astroviruses (n=9) and a human MLB1 astrovirus were detected in human faecal samples (n=622). Novel astroviruses were detected from 1.6 % of the faecal samples of urban brown rat (Rattus norvegicus) (n=441), indicating the prevalence of astrovirus infection in rats might be much lower than that recently observed in bats. These rat astroviruses were phylogenetically related to recently discovered human astroviruses MLB1 and MLB2, suggesting that the MLB viruses and these novel rat astroviruses may share a common ancestor.


title: Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?

text: Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.


title: The Individual and Population Genetics of Antibody Immunity

text: Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype–phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. In this opinion article, we outline interconnections between IG genomic diversity and Ab-expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine.


title: Dynamics of Multi-stage Infections on Networks

text: This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider.


title: Pneumonia

text: This article is an updated version of the previous edition article by Mariano Esperatti, Antoni Torres Marti, volume 5, pp. 133–144, © 2008, Elsevier Inc.


title: Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy

text: Covid‑19 origin and transmission to humans. Covid‑19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid‑19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS‑CoV‑2 transmission. However, the source(s) and transmission routine(s) of SARS‑CoV‑2 remain elusive' (1).


title: A blueprint for recovery for the postcoronavirus (COVID‐19) world

text: Novel coronavirus (COVID-19) is changing society. In the last several weeks, infections and deaths have accumulated, even as we attempt to 'shelter in place' and stay 'healthy at home'. This unprecedented time has influenced behavior and permitted much contemplation, gratitude and prayer. Our thoughts during this time have focused on our emergence from the pandemic and what reopening may look like in the post-coronavirus world. Reopening will benefit from the acronym "RPM", an acronym I (CSM) teach my students for management of dental patients who suffer from a variety of illnesses and infections. Here, the 'R" stands for risk assessment and reduction, the first step in the sequence. The 'P' stands for prevention, and 'M' stands for manage the problem. If 'R' and 'P' are well conceived and implemented, often there is no need to apply 'M'.


title: Antisense Antimicrobial Therapeutics

text: Antisense antimicrobial therapeutics are synthetic oligomers that silence expression of specific genes. This specificity confers an advantage over broad-spectrum antibiotics by avoiding unintended effects on commensal bacteria. The sequence-specificity and short length of antisense antimicrobials also pose little risk to human gene expression. Because antisense antimicrobials are a platform technology, they can be rapidly designed and synthesized to target almost any microbe. This reduces drug discovery time, and provides flexibility and a rational approach to drug development. Recent work has shown that antisense technology has the potential to address the antibiotic-resistance crisis, since resistance mechanisms for standard antibiotics apparently have no effect on antisense antimicrobials. Here, we describe current reports of antisense antimicrobials targeted against viruses, parasites, and bacteria.


No evidence of MERS‐CoV in Ghanaian Hajj pilgrims: cautious interpretation is needed


title: Towards a pharmacochemical hypothesis of the prophylaxis of SARS-CoV-2 by psychoactive substances

text: An increasing body of evidence suggests a protective effect of some psychoactive substances against SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus type 2). Recent findings suggest that patients with psychiatric disorders are less affected by SARS-CoV-2 than their caregivers, which may seem surprising given some of the frequent risk factors for an unfavorable course of the disease (e.g., obesity, diabetes, cardiovascular and pulmonary diseases). We propose here a mixed pharmacoepidemiological and pharmacochemical hypothesis to explain these findings. A number of psychotropic drugs exhibit activities against coronaviruses (Middle East Respiratory Syndrome coronavirus (MERS-CoV), the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and the Infectious Bronchitis Virus (IBV)) and have been put forward as potentially anti-SARS-CoV-2. These treatments include numerous mee-too drugs (chemically and pharmacologically linked to those which have demonstrated anti-SARS-CoV-2 efficacy) which are frequently prescribed in psychiatric settings. Taken alone or in polypharmacy, these drugs could have a prophylactic anti-SARS-CoV-2 effect, explaining the unexpectedly low proportion of patients with psychiatric disorders and COVID-19. Associated factors such as nicotine can also be considered in the context of a broad chemoprophylactic hypothesis in patients with psychiatric disorders taking different psychoactive substances.


Challenges of Neurosurgery Education During the COVID Pandemic: A US Perspective


title: Temporal changes in immune blood cell parameters in COVID‐19 infection and recovery from severe infection

text: Since emerging in China in December 2019, the infection caused by SARS-CoV-2, COVID-19, has infected more than 3 million people worldwide (Johns Hopkins University and Medicine: Coronavirus Resource Center). Since then, clusters of infections have emerged in Singapore, particularly among younger workers in communal living environments. The spectrum of COVID-19 infection ranges from mild respiratory illness, to viral pneumonia and life-threatening acute respiratory distress syndrome in up 15-20% (Huang, et al 2020, Wu and McGoogan 2020).


title: Use of an improved quantitative polymerase chain reaction assay to determine differences in human rhinovirus viral loads in different populations

text: Abstract Human rhinoviruses (HRV) frequently cause acute respiratory infections and chronic respiratory disease exacerbations. However, testing is not generally offered. We developed a modified HRV quantitative polymerase chain reaction (qPCR) assay to assess viral loads in the community and hospital patients. The assay had a lower limit of detection of 2 log10 viral copies/mL and displayed linearity over 5 log10 viral copies, with a lower limit of quantitation of 4 log10 viral copies/mL. Mean viral loads (95% confidence interval) for hospitalized children, university students, and institutionalized elderly, were 7.08 log10 viral copies/mL (6.7–7.5), 6.87 log10 viral copies/mL (6.5–7.2), and 7.09 log10 viral copies/mL (6.9–7.3), respectively (P = 0.67). Serial specimens of 14 university students showed a decrease of mean viral loads from 6.36 log10 viral copies/mL on day 1 to 2.32 log10 viral copies/mL 7 days past symptom onset (P < 0.001). Using an HRV qPCR, we showed that viral loads did not differ between the community and hospitalized populations and significantly decreased following symptoms onset in healthy individuals.


title: Identification of Trimeric Peptides That Bind Porcine Parvovirus from Mixtures Containing Human Blood Plasma

text: Virus contamination in human therapeutics is of growing concern as more therapeutic products from animal or human sources come into the market. All biopharmaceutical processes are required to have at least two distinct viral clearance steps to remove viruses. Most of these steps work well for enveloped viruses and large viruses, whether enveloped or not. That leaves a class of small non‐enveloped viruses, like parvoviruses and hepatitis A, which are not easily removed by these typical steps. In this study, we report the identification of trimeric peptides that bind specifically to porcine parvovirus (PPV) and their potential use to remove this virus from process solutions. All of the trimeric peptides isolated completely removed all detectable PPV from buffer in the first nine column volumes, corresponding to a clearance of 4.5–5.5 log of infectious virus. When the virus was spiked into a more complex matrix consisting of 7.5% human blood plasma, one of the trimers, WRW, was able to remove all detectable PPV in the first three column volumes, after which human blood plasma began to interfere with the binding of the virus to the peptide resin. These trimer resins removed considerably more virus than weak ion exchange resins. The results of this work indicate that small peptide ligand resins have the potential to be used in virus removal processes where removal of contaminating virus is necessary to ensure product safety.


title: Seroepidemiology of Human Bocavirus Infection in Jamaica

text: BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean. METHODS: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA). RESULTS: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica. CONCLUSION: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world.


title: Is there a Role for Hypofractionated Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer? A Propensity Score Matched Analysis

text: ABSTRACT Introduction Various radiation schedules are used in concurrent chemoradiotherapy for limited-stage small cell lung cancer (LS-SCLC). As there is currently no randomized evidence comparing hypofractionated (HFRT) and conventionally-fractionated radiotherapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC. Methods LS-SCLC patients treated between 2000-2013 with HFRT (40Gy/15, 45Gy/15, 45Gy/20 fractions) or CFRT (60Gy/30 or 66Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events. Results In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, smoked more often concurrently with treatment, had higher ECOG performance status, different T and N stage patterns, and more commonly received concurrent chemoradiotherapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts respectively. There was no difference in OS (P=0.724), PFS (P=0.862), any pulmonary (P=0.350), or esophageal (P=0.097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P=0.020). Multivariable Cox regression also revealed no differences in OS (P=0.886) or PFS (P=0.717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed. Conclusion In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies.


The adoption and implementation of digital healthcare in the post COVID-19 Era


title: Comparison of bovine coronavirus (BCV) antigens: Monoclonal antibodies to the spike glycoprotein distinguish between vaccine and wild-type strains

text: Abstract Monoclonal antibodies (MAbs) against two major structural proteins of the cell-adapted Mebus strain of bovine coronavirus (BCV-L9) were produced and characterized. Seven MAbs reacted with the peplomeric glycoprotein, gp100/S, while three MAbs reacted with the nucleoprotein p53/N in Western blot analysis of BCV polypeptides. MAbs to gp100/S reacted with discontinuous epitopes of gp100/S in Westerns under mild but not under standard denaturing conditions. In contrast, MAbs to p53/N reacted in both types of Westerns, and those epitopes were thus continuous. MAbs to p53/N failed to neutralize BCV infectivity, while 4 MAbs to gp100/S neutralized BCV effectively. Cross reactivity of MAbs to gp100/S specified by five virulent wild-type strains and two high passage, cell-culture-adapted strains in mildly denaturing Westerns and neutralization assays indicated that two epitopes were conserved in all seven strains, while two epitopes of the avirulent strains were not detected in the wild-type strains. Non-neutralizing MAbs of gp100/S reacted with all seven strains in Westerns with the exception of one MAb that was specific for the highly cell-adapted strain BCV-L9.


title: Disease-specific B cell epitopes for serum antibodies from patients with severe acute respiratory syndrome (SARS) and serologic detection of SARS antibodies by epitope-based peptide antigens

text: Severe acute respiratory syndrome (SARS) has emerged as a highly contagious, sometimes fatal disease. To find disease-specific B cell epitopes, phage-displayed random peptide libraries were panned on serum immunoglobulin (Ig) G antibodies from patients with SARS. Forty-nine immunopositive phage clones that bound specifically to serum from patients with SARS were selected. These phageborne peptides had 4 consensus motifs, of which 2 corresponded to amino acid sequences reported for SARS-associated coronavirus (SARSCoV). Synthetic peptide binding and competitive-inhibition assays further confirmed that patients with SARS generated antibodies against SARS-CoV. Immunopositive phage clones and epitope-based peptide antigens demonstrated clinical diagnostic potential by reacting with serum from patients with SARS. Antibody-response kinetics were evaluated in 4 patients with SARS, and production of IgM, IgG, and IgA were documented as part of the immune response. In conclusion, B cell epitopes of SARS corresponded to novel coronavirus. Our epitope-based serologic test may be useful in laboratory detection of the virus and in further study of the pathogenesis of SARS.


Editorial: the 18th annual Nucleic Acids Research web server issue 2020


title: Why we should not stop giving aspirin to pregnant women during the COVID‐19 pandemic

text: With the current outbreak and spread of the coronavirus disease 2019 (COVID-19) worldwide many questions arise. There have been issued precautions regarding the use of anti-inflammatory medications, including aspirin. To our knowledge, there is insufficient data to suggest an increased risk between prophylactic use of low-dose aspirin and progression of COVID-19 infection in pregnant women at risk of placental complications. This article is protected by copyright. All rights reserved.


title: Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol

text: INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12–64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48–72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.


title: Influence of Dietary Fat and Protein on Body Composition of Jersey Bull Calves 1

text: Abstract Thirty-nine bull calves between 6 and 9 d of age, were assigned to either baseline slaughter or 1 of 4 diets to determine the influence of dietary fat and protein content, at 2 levels of intake, on growth and body composition changes. Calves were assigned to the following diets a 28.5% protein and 16.4% fat milk replacer [MR; 29/16 (n=9)], 27.3% protein and 33.4% fat MR [27/33 (n=8)], 20.6% protein and 20.6% fat MR [20/20 (8)], or whole milk [WM (n=8)]. Calves fed 27/33, 29/16, and WM received 180 g/d of CP to support 650g of ADG based on predictions from the 2001 NRC. Calves were fed 3 times daily for 4 wk. Weight, hip height, wither height, heart girth, and body length were measured weekly. Weekly plasma samples were analyzed for plasma urea nitrogen, nonesterified fatty acids, and glucose. A subset of calves from each treatment was killed [29/16 (n=7), 27/33 (n=6), 20/20 (n=6), and WM (n=5)] at the end of wk 4 of treatment; processed for whole-body analysis of fat, protein, ash, and DM; and compared with baseline slaughter calves to estimate composition of empty BW gain. Calves did not differ in average weekly scour score or medication days. Feed efficiency and ADG were greatest for calves fed WM and least for calves fed 20/20; calves fed 29/16 and 27/33 did not differ. Calves fed 27/33 or WM had the greatest % body fat and gained more grams of fat than calves fed other diets. Calves fed 29/16 or 20/20 had similar % fat in empty body as baseline. Differences in % CP, % ash, or % water in empty body and empty BW gain were not detected. Calves fed 27/33 had a trend toward higher NEFA in wk 1 and 2 than calves fed 29/16 or WM. Growth of calves fed 27/33 and 29/16 were similar except that calves fed 29/16 had lower body fat % than calves fed 27/33. Calves on all diets gained less than predicted by the 2001 NRC.


title: Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life—a case study

text: BACKGROUND: The perinatal period carries the highest risk for stroke in childhood; however, the pathophysiology is poorly understood and preventive, prognostic, and therapeutic strategies are not available. A new pathophysiological model describes the development of neonatal arterial ischemic stroke (NAIS) as the combined result of prenatal inflammation and hypoxic–ischemic insult. Neuroinflammation and a systemic inflammatory response are also important features of NAIS. Identifying key players of the inflammatory system is in the limelight of current research. CASE PRESENTATION: We present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from the first month of life. All neonates were admitted with the initial diagnosis of hypoxic ischemic encephalopathy (HIE); however, early MRI examination revealed NAIS. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Peripheral blood mononuclear cells were assessed with flow cytometry and plasma cytokine levels were measured. Pooled data from the cohort of four NAIS patients were compared to infants with HIE. At 6 and 72 h of age, the prevalence of IL10+ CD8+ lymphocytes remained lower in NAIS. At 6 h, CD8+ lymphocytes in NAIS produced more IL-17. At 72 h, CD8+ cells produced more IL-6 in severe HIE than in NAIS, but IL-6 production remained elevated in CD8 cells at 1 month in NAIS, while it decreased in HIE. At 1 week, the prevalence of TGF-β + lymphocytes prone to enter the CNS was elevated in NAIS. On the other hand, by 1 month of age, the prevalence of TGF-β + CD4+ lymphocytes decreased in NAIS compared to HIE. At 72 h, we found elevated plasma levels of IL-5, MCP-1, and IL-17 in NAIS. By 1 month, plasma levels of IL-4, IL-12, and IL-17 decreased in NAIS but remained elevated in HIE. CONCLUSIONS: Differences in the cytokine network are present between NAIS and HIE. CD8 lymphocytes appear to shift towards the pro-inflammatory direction in NAIS. The inflammatory response appears to be more pronounced at 72 h in NAIS but decreases faster, reaching lower plasma levels of inflammatory markers at 1 month.


title: Saccharomyces cerevisiae: A useful model host to study fundamental biology of viral replication

text: Abstract Understanding the fundamental steps of virus life cycles including virus–host interactions is essential for the design of effective antiviral strategies. Such understanding has been deferred by the complexity of higher eukaryotic host organisms. To circumvent experimental difficulties associated with this, systems were developed to replicate viruses in the yeast Saccharomyces cerevisiae. The systems include viruses with RNA and DNA genomes that infect plants, animals and humans. By using the powerful methodologies available for yeast genetic analysis, fundamental processes occurring during virus replication have been brought to light. Here, we review the different viruses able to direct replication and gene expression in yeast and discuss their main contributions in the understanding of virus biology.


title: Serosurvey of Coxiella burnetii (Q fever) in Dromedary Camels (Camelus dromedarius) in Laikipia County, Kenya

text: Dromedary camels (Camelus dromedarius) are an important protein source for people in semi‐arid and arid regions of Africa. In Kenya, camel populations have grown dramatically in the past few decades resulting in the potential for increased disease transmission between humans and camels. An estimated four million Kenyans drink unpasteurized camel milk, which poses a disease risk. We evaluated the seroprevalence of a significant zoonotic pathogen, Coxiella burnetii (Q fever), among 334 camels from nine herds in Laikipia County, Kenya. Serum testing revealed 18.6% positive seroprevalence of Coxiella burnetii (n = 344). Increasing camel age was positively associated with C. burnetii seroprevalence (OR = 5.36). Our study confirmed that camels living in Laikipia County, Kenya, have been exposed to the zoonotic pathogen, C. burnetii. Further research to evaluate the role of camels in disease transmission to other livestock, wildlife and humans in Kenya should be conducted.


Antimicrobials


title: Chapter Eight Nanoparticle-Based Peptide Vaccines

text: Abstract The use of peptide antigens for vaccination, compared with traditional vaccines, has advantages such as purity and low risk of adverse effects and disadvantages such as weak immunogenicity and necessitates administration with an adjuvant. To benefit from these advantages and at the same time overcome the disadvantages, a wide variety of nanoparticles are being actively studied for the development of peptide-based vaccines, in which the antigen either is loaded on the particle surface or is present within the particle. In this chapter, we will provide a brief overview of synthetic peptide–based vaccine research, with special attention on multiple antigen-presenting peptide vaccines. Further, we will introduce the current approaches for the development of nanoparticle-based peptide vaccines, which use well-characterized synthetic peptide antigens with facile chemical modifications (eg, attachment of lipid chain(s) or self-assembling peptide sequences). These modifications can be employed to induce peptide self-assembly into nanoparticles, which present multiple copies of peptide antigens on their surface.