title: Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge

text: Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads rapidly after entering naïve pig populations. The objectives were to (1) compare the disease course following inoculation with PEDV isolate US/Colorado/2013 in naïve 10 day and 8 week-old pigs, and (2) contrast the naïve response to homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1 (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age) and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2 pigs received a homologous challenge at 8 weeks of age. Following primary or secondary inoculation, 3–10 pigs were euthanized at days post-inoculation (dpi) 1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14 fecal shedding patterns were also similar. While both age groups had seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44. In homologous challenged pigs, no clinical signs or lesions were found, and PEDV fecal shedding was restricted to less than 10% of the pigs indicating the existence of homologous protection 44 days after initial PEDV exposure.


title: A Role for Neutrophils in Viral Respiratory Disease

text: Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.


A Pneumonia Case Associated with Type 2 Polio Vaccine Strains


Short‐term Skin Reactions Following Use of N95 Respirators and Medical Masks


Immune mechanisms in inflammatory polyneuropathy


title: A cluster randomised trial of cloth masks compared with medical masks in healthcare workers

text: OBJECTIVE: The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks. SETTING: 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam. PARTICIPANTS: 1607 hospital HCWs aged ≥18 years working full-time in selected high-risk wards. INTERVENTION: Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks. MAIN OUTCOME MEASURE: Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection. RESULTS: The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%. CONCLUSIONS: This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12610000887077.


CORONAVIRUS AND RADIOLOGY. CONSIDERATIONS ON THE CRISIS


El diagnostico COVID-19 a través de la imagen


Mechanical Risks of Ventilator Sharing in the COVID-19 Era: a Simulation- Based Study


title: Surface plasmon resonance applications in clinical analysis

text: In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. Thus, we report in this review the state of the art of clinical target detection with SPR-based biosensors in complex matrices (e.g., serum, saliva, blood, and urine) as well as in standard solution when innovative approaches or advanced instrumentations were employed for improved detection. The principles of SPR-based biosensors are summarized first, focusing on the physical properties of the transducer, on the assays design, on the immobilization chemistry, and on new trends for implementing system analytical performances (e.g., coupling with nanoparticles (NPs). Then we critically review the detection of analytes of interest in molecular diagnostics, such as hormones (relevant also for anti-doping control) and biomarkers of interest in inflammatory, cancer, and heart failure diseases. Antibody detection is reported in relation to immune disorder diagnostics. Subsequently, nucleic acid targets are considered for revealing genetic diseases (e.g., point mutation and single nucleotides polymorphism, SNPs) as well as new emerging clinical markers (microRNA) and for pathogen detection. Finally, examples of pathogen detection by immunosensing were also analyzed. A parallel comparison with the reference methods was duly made, indicating the progress brought about by SPR technologies in clinical routine analysis.


title: Apoptosis induced in vivo by new type gosling viral enteritis virus

text: In this study, apoptosis was induced by new type gosling viral enteritis virus (NGVEV) in experimentally infected goslings is reported in detail for the first time. After 3-day-old goslings were orally inoculated with a NGVEV-CN strain suspension, the time course of NGVEV effects on apoptotic morphological changes of the internal tissues was evaluated. These changes were observed by histological analysis with light microscopy and ultrastructural analysis with transmission electron microscopy. DNA fragmentation was assessed with a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and DNA ladder analysis. A series of characteristic apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, plasma membrane blebbing, and formation of apoptotic bodies were noted. Apoptosis was readily observed in the lymphoid and gastrointestinal organs, and sporadically occurred in other organs after 3 days post-infection (PI). The presence and quantity of TUNEL-positive cells increased with infection time until 9 days PI. DNA extracted from the NGVEV-infected gosling cells displayed characteristic 180~200 bp ladders. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages, monocytes, and epithelial and intestinal cells. Necrosis was subsequently detected during the late NGVEV-infection phase, which was characterized by cell swelling, plasma membrane collapse, and rapidly lysis. Our results suggested that apoptosis may play an important role in the pathogenesis of NGVE disease.


title: COVID-19 et Insuffisance rénale aigue en réanimation

text: Résumé L’atteinte rénale est une complication fréquemment rencontrée chez les patients hospitalisés en unité de soins intensifs pour syndrome de détresse respiratoire aigüe (SDRA) du à la COVID-19. Sa prévalence semble différente à travers le monde. Plusieurs mécanismes physiopathologiques sont impliqués, parmi lesquelles une hypoperfusion rénale liée à la ventilation mécanique, au sepsis et à l’orage cytokinique, ainsi qu’une toxicité directe du virus sur les cellules tubulaires proximales et les podocytes, médiée par les récepteurs de conversion de l’angiotensine 2 (ACE 2) et les protéases TMPRSS. Le recours à l’épuration extra rénale (EER) est de l’ordre de 20% chez les patients de réanimation. La dialyse est rendue difficile par l’état d’hypercoagulabilité des patients atteints du SARS-Cov2, qui provoque des thromboses précoces du filtre. Summary Renal impairment is a common complication in patients hospitalized in intensive care unit for acute respiratory distress syndrome (ARDS) due to COVID-19 infection. However, the prevalence of SARS-covid2 kidney injury is difficult to estimate worldwide. Several pathophysiological mechanisms are involved; including decreased renal perfusion related to mechanical ventilation, sepsis and cytokines release, as well as direct virus toxicity on proximal tubular cells and podocytes, mediated by angiotensin 2 conversion receptors (ACE 2) and TMPRSS proteases. More than 20% of ICU COVID-19 patients require extra renal replacement therapy (ERT) for acute renal failure that is made difficult by the hypercoagulable state of these patients, responsible for filter thrombosis.


title: Exploring the Major Factors Influencing Consumer Selection of Travel Agencies in a Regional Setting

text: The research reported in this article explores why consumers choose to book their travel arrangements with travel agencies in regional settings. Consumers can now access online bookings for airlines, accommodation, transportation, sightseeing tours and other related products, so why do they still go to travel agencies for reservations? This article identifies the attributes consumers seek in a travel agency or consultant and determines the relative importance of these in their selection process. The research was conducted in two stages. The first stage was a series of in-depth interviews with 10 travel agency users and three travel consultants. The second stage was a mail-out survey of 400 users of travel agencies in the Darling Downs area of Queensland, Australia. Despite its regionality, the region is a significant consumer of travel with approximately eight agencies in the city of Toowoomba alone. The in-depth interviews highlighted the need to de-emphasise two particular agency attributes, agency promotion and adequate brochure provision, from the research questions and replace these with parking and travel reward programs as factors worthy of investigation. Survey results revealed that there were 12 significant attributes impacting on consumer selection and, of these, the most important were the knowledge and experience of consultants, and the helpfulness and friendliness of consultants. Of particular note was that these attributes related to the consultant and not the agency per se. Travel reward programs were seen as the least influential in this research.


title: Spillover and pandemic properties of zoonotic viruses with high host plasticity

text: Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.


title: Predictive value of C-reactive protein for the diagnosis of meningitis in febrile infants under 3 months of age in the emergency department

text: BACKGROUND: Fever is a common cause of pediatric consultation in the emergency department. However, identifying the source of infection in many febrile infants is challenging because of insufficient presentation of signs and symptoms. Meningitis is a critical cause of fever in infants, and its diagnosis is confirmed invasively by lumbar puncture. This study aimed to evaluate potential laboratory markers for meningitis in febrile infants. METHODS: We retrospectively analyzed infants aged <3 months who visited the emergency department of our hospital between May 2012 and May 2017 because of fever of unknown etiology. Clinical information and laboratory data were evaluated. Receiver operating characteristic (ROC) curves were constructed. RESULTS: In total, 145 febrile infants aged <3 months who underwent lumbar punctures were evaluated retrospectively. The mean C-reactive protein (CRP) level was significantly higher in the meningitis group than in the non-meningitis group, whereas the mean white blood cell count or absolute neutrophil count (ANC) did not significantly differ between groups. The area under the ROC curve (AUC) for CRP was 0.779 (95% confidence interval [CI], 0.701–0.858). The AUC for the leukocyte count was 0.455 (95% CI, 0.360–0.550) and that for ANC was 0.453 (95% CI, 0.359–0.547). The CRP cut-off value of 10 mg/L was optimal for identifying possible meningitis. CONCLUSION: CRP has an intrinsic predictive value for meningitis in febrile infants aged <3 months. Despite its invasiveness, a lumbar puncture may be recommended to diagnose meningitis in young, febrile infants with a CRP level >10 mg/L.


title: Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease Inhibitors

text: In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL‐3) of the SARS‐CoV 3CL protease. A novel C (2)‐symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μm). We believe that this approach has provided a platform for further lead optimization.[Image: see text]


title: Role of Human Polyomaviruses in Respiratory Tract Disease in Young Children

text: KI virus was detected in respiratory secretions of 8/367 (2.2%) symptomatic and 0/96 asymptomatic children (p = 0.215). WU virus was detected in 26/367 (7.1%) symptomatic and 6/96 (6.3%) asymptomatic children (p = 1.00). These human polyomaviruses may not independently cause respiratory tract disease in young children.


title: Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS‐CoV‐2

text: There remain unanswered questions concerning mother‐to‐child‐transmission (MTCT) of SARS‐CoV‐2. Despite reports of neonatal COVID‐19, SARS‐CoV‐2 has not been consistently isolated in perinatal samples thus, definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal‐fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID‐19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. While RT‐PCR of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID‐19 was reported in eight studies, two of which were based on the detection of SARS‐CoV‐2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID‐19. The paucity of placental co‐expression of ACE‐2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS‐CoV‐2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE‐2 thus, tissue susceptibility may be broader than currently known. Further spatial‐temporal studies are needed to determine the true potential for transplacental migration. This article is protected by copyright. All rights reserved.


Ion Channels Formed by SARS Coronavirus Envelope Protein: Lipid Regulation of Conductance and Selectivity


title: Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation

text: Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression.


Letter to the Editor Regarding: “An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)” —Secondhand and Thirdhand Smoke As Potential Sources of COVID-19


docid: strhszpd

title: Current advancements and potential strategies in the development of MERS-CoV vaccines

text: Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.


docid: euxtklwq

title: Meta‐analysis of chest CT features of patients with COVID‐19 pneumonia

text: The objective of this paper is to perform a meta‐analysis regarding the chest computed tomography (CT) manifestations of coronavirus disease‐2019 (COVID‐19) pneumonia patients. PubMed, Embase, and Cochrane Library databases were searched from 1 December 2019 to 1 May 2020 using the keywords of “COVID‐19 virus,” “the 2019 novel coronavirus,” “novel coronavirus,” and “COVID‐19.” Studies that evaluated the CT manifestations of common and severe COVID‐19 pneumonia were included. Among the 9736 searched results, 15 articles describing 1453 common patients and 697 severe patients met the inclusion criteria. Based on the CT images, the common patients were less frequent to exhibit consolidation (odds ratio [OR] = 0.31), pleural effusion (OR = 0.19), lymphadenopathy (OR = 0.17), crazy‐paving pattern (OR = 0.22), interlobular septal thickening (OR = 0.27), reticulation (OR = 0.20), traction bronchiectasis (OR = 0.40) with over two lobes involved (OR = 0.07) and central distribution (OR = 0.18) while more frequent to bear unilateral pneumonia (OR = 4.65) involving one lobe (OR = 13.84) or two lobes (OR = 6.95) when compared with severe patients. Other CT features including ground‐glass opacities (P = .404), air bronchogram (P = .070), nodule (P = .093), bronchial wall thickening (P = .15), subpleural band (P = .983), vascular enlargement (P = .207), and peripheral distribution (P = .668) did not have a significant association with the severity of the disease. No publication bias among the selected studies was suggested (Harbord's tests, P > .05 for all.) We obtained reliable estimates of the chest CT manifestations of COVID‐19 pneumonia patients, which might provide an important clue for the diagnosis and classification of COVID‐19 pneumonia.


title: Antibody responses to respiratory coronavirus infections of cattle during shipping fever pathogenesis

text: Antibody responses against respiratory bovine coronavirus (RBCV) infections were monitored in cattle from the onset of a naturally occurring severe shipping fever (SF) epizootic to complete recovery of affected cattle or fatal outcomes. The infection with RBCV was detected in nasal secretions of 86 cattle, and 81 of them developed acute respiratory tract disease, including fatal pneumonia. Cattle nasally shedding RBCV at the beginning of the epizootic experienced characteristic primary immune responses with specific antibodies for hemagglutinin-esterase (HE) and spike (S) glycoproteins. Virus shedding in nasal secretions of the majority of the cattle ceased between days 7 and 14 with the appearance of HE- and S-specific antibodies. Nasal samples and lung tissues from 9 of the 10 fatal cases had high titers of RBCV, but these cattle had only IgM responses to RBCV infections. Cattle remaining negative in RBCV isolation tests entered this epizootic with antibodies against HE and S. Protection against respiratory tract disease was apparently associated with high level of opsonic and virus-neutralizing IgG2. The HE and S glycoproteins were recognized earliest by the bovine immune system while the N protein induced antibody responses during the later stage of initial infection and the early stage of reinfection. The membrane (M) glycoprotein was the least immunogenic of the major viral structural proteins.


title: 28 New and Emerging Infections of the Lung

text: Abstract In this era of rapid globalization and frequent travel, emerging viral infections have gained an immense potential to spread at an unprecedented speed and scale compared with the past. This poses a significant challenge to coordinated international efforts in global surveillance and infection control. Significantly, respiratory viral infections, spread mostly via droplet transmission, are extremely contagious and have caused significant morbidity and mortality during outbreaks in the last decade. Molecular diagnostics via reverse transcriptase polymerase chain reaction (RT-PCR) have been key in the rapid diagnosis of most of these viral infections. However, a high index of suspicion and early institution of appropriate isolation measures remain as the mainstay in the control and containment of the spread of these viral infections. Although treatment for most of the viral infections remains supportive, efficacious antiviral agents against influenza infections exist. The infections discussed in this chapter include those first described in the 2000s: Middle East respiratory syndrome coronavirus (MERS-CoV) and metapneumovirus and rhinovirus C as well as those that have been described in the past but have reemerged in the last decade in outbreaks resulting in significant morbidity and mortality, including adenovirus, influenza virus, and enterovirus D68 (EV-D68).


title: Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19

text: SARS-CoV-2 is causative agent of COVID-19, which is responsible for severe social and economic disruption globally. Lack of vaccine or antiviral drug with clinical efficacy suggested that drug repurposing approach may provide a quick therapeutic solution to COVID-19. Nonstructural protein-15 (NSP15) encodes for an uridylate-specific endoribonuclease (EndoU) enzyme, essential for virus life cycle and an attractive target for drug development. We have performed in silico based virtual screening of FDA approved compounds targeting EndoU in search of COVID-19 drugs from commercially available approved molecules. Two drugs Glisoxepide and Idarubicin used for treatment for diabetes and leukemia, respectively, were selected as stronger binder of EndoU. Both the drugs bound to the active site of the viral endonuclease by forming attractive intermolecular interactions with catalytically essential amino acid residues, His235, His250, and Lys290. Molecular dynamics simulation studies showed stable conformation dynamics upon drugs binding to endoU. The binding free energies for Glisoxepide and Idarubicin were calculated to be –141 ± 11 and –136 ± 16 kJ/mol, respectively. The IC(50) were predicted to be 9.2 µM and 30 µM for Glisoxepide and Idarubicin, respectively. Comparative structural analysis showed the stronger binding of EndoU to Glisoxepide and Idarubicin than to uridine monophosphate (UMP). Surface area calculations showed buried are of 361.8Å(2) by Glisoxepide which is almost double of the area occupied by UMP suggesting stronger binding of the drug than the ribonucleotide. However, further studies on these drugs for evaluation of their clinical efficacy and dose formulations may be required, which may provide a quick therapeutic option to treat COVID-19. Communicated by Ramaswamy H. Sarma


Competition law in times of crisis—tackling the COVID-19 challenge


CoVID-19 vs. epilepsy: It is time to move, act and encourage physical exercise’?


title: Virus-Vectored Ebola Vaccines

text: The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014−2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.


title: A novel coronavirus capable of lethal human infections: an emerging picture

text: SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.


docid: xbsvofir

title: The threat of climate change to non-dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets

text: BACKGROUND: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. METHODS: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. RESULTS: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. CONCLUSION: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.


title: Neuropsychiatric Symptoms in an Adolescent Boy with Multisystem Inflammatory Syndrome in Children (MIS-C)

text: BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) related to coronavirus disease-2019 (COVID-19) is an emergent syndrome affecting children globally in the wake of the SARS-CoV-2 pandemic. The clinical presentation has similarities to Kawasaki disease and toxic shock syndrome. As knowledge of the cardiac and gastrointestinal manifestations has been emerging, little is known about the impact on the brain. METHOD: This case describes a 14-year-old boy who developed prominent neuropsychiatric symptoms including delirium followed by impairments in executive functioning in the context of MIS-C with positive SARS-CoV-2 antibodies. These symptoms improved in correlation with improvements in inflammatory markers. RESULTS: Neuropsychiatric manifestations including confusion, irritability, and headaches have been reported in pediatric patients with MIS-C. Potential mechanisms include direct neurotropic effect of SARS-CoV-2, secondary effects of systemic inflammation, and/or adverse side effects of treatment. CONCLUSIONS: MIS-C is a novel and poorly understood syndrome related to SARS-CoV-2 with effects on multiple organ systems including the central nervous system. As additional cases are reported and research expands, so too will our understanding of the neuropsychiatric manifestations. Better understanding of the underlying pathophysiology would aid in determining targeted interventions.


Prevalence of antibodies against COVID-19 in the staff of a COVID-19 regular ward


docid: pkniwunl

title: “The storm has arrived”: the impact of SARS-CoV-2 on medical students

text: In a few weeks, the global community has witnessed, and for some of us experienced first-hand, the human costs of the COVID-19 pandemic. There is incredible variability in how countries are choosing to thwart the disease’s outbreak, sparking intense discussions around what it means to teach and learn in the era of COVID-19, and more specifically, the role medical students play in the midst of the pandemic. A multi-national and multi-institutional group made up of a dedicated medical student from Austria, passionate clinicians and educators from Switzerland, and a PhD scientist involved in Medical Education from Canada, have assembled to summarize the ingenious ways medical students around the world are contributing to emergency efforts. They argue that such efforts change COVID-19 from a “disruption” to medical students learning to something more tangible, more important, allowing students to become stakeholders in the expansion and delivery of healthcare.


title: Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres

text: Transposable elements are omnipresent in eukaryotic genomes and have a profound impact on chromosome structure, function and evolution. Their structural and functional diversity is thought to be reasonably well-understood, especially in retroelements, which transpose via an RNA intermediate copied into cDNA by the element-encoded reverse transcriptase, and are characterized by a compact structure. Here, we report a novel type of expandable eukaryotic retroelements, which we call Terminons. These elements can attach to G-rich telomeric repeat overhangs at the chromosome ends, in a process apparently facilitated by complementary C-rich repeats at the 3′-end of the RNA template immediately adjacent to a hammerhead ribozyme motif. Terminon units, which can exceed 40 kb in length, display an unusually complex and diverse structure, and can form very long chains, with host genes often captured between units. As the principal polymerizing component, Terminons contain Athena reverse transcriptases previously described in bdelloid rotifers and belonging to the enigmatic group of Penelope-like elements, but can additionally accumulate multiple cooriented ORFs, including DEDDy 3′-exonucleases, GDSL esterases/lipases, GIY-YIG-like endonucleases, rolling-circle replication initiator (Rep) proteins, and putatively structural ORFs with coiled-coil motifs and transmembrane domains. The extraordinary length and complexity of Terminons and the high degree of interfamily variability in their ORF content challenge the current views on the structural organization of eukaryotic retroelements, and highlight their possible connections with the viral world and the implications for the elevated frequency of gene transfer.


title: Difficulty of downscaling the precautions for coronavirus disease-19 based on negative throat polymerase chain results in the early phase of infection

text: Abstract We here report a case of coronavirus disease-19 (COVID-19) in Japan in which the initial throat swab polymerase chain reaction result was negative The possibility of false-negative results in the early phase of disease suggest reconsideration of the feasibility of a community or national infection control framework to prevent transmission. We recommend establishing an alternative feasible system, such as self-isolation by contact history in non-endemic community and by symptoms in endemic community, not relying on the PCR examination, to minimize this ongoing COVID-19 outbreak. Further rapid accumulation of knowledge including incubation period, clinical course and types of transmission is warranted to control this outbreak.


docid: mlshkaid

title: COVID-19: Lessons for an Urban(izing) World

text: The COVID-19 crisis has changed the face of many of our cities and questioned how we should manage urban life in the wake of a pandemic. This Commentary points to the need to learn urban governance lessons and to the potential value of urban experimentation in crisis.


title: Coronavirus Genomics and Bioinformatics Analysis

text: The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999–2002, with estimated substitution rate of 4×10(−4) to 2×10(−2) substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.


title: Just-in-Time Simulation to Guide Workflow Design for Coronavirus Disease 2019 Difficult Airway Management

text: OBJECTIVES: The coronavirus disease 2019 pandemic has required that hospitals rapidly adapt workflows and processes to limit disease spread and optimize the care of critically ill children. DESIGN AND SETTING: As part of our institution’s coronavirus disease 2019 critical care workflow design process, we developed and conducted a number of simulation exercises, increasing in complexity, progressing to intubation wearing personal protective equipment, and culminating in activation of our difficult airway team for an airway emergency. PATIENTS AND INTERVENTIONS: In situ simulations were used to identify and rework potential failure points to generate guidance for optimal airway management in coronavirus disease 2019 suspected or positive children. Subsequent to this high-realism difficult airway simulation was a real-life difficult airway event in a patient suspected of coronavirus disease 2019 less than 12 hours later, validating potential failure points and effectiveness of rapidly generated guidance. MEASUREMENTS AND MAIN RESULTS: A number of potential workflow challenges were identified during tabletop and physical in situ manikin-based simulations. Experienced clinicians served as participants, debriefed, and provided feedback that was incorporated into local site clinical pathways, job aids, and suggested practices. Clinical management of an actual suspected coronavirus disease 2019 patient with difficult airway demonstrated very similar success and anticipated failure points. Following debriefing and assembly of a success/failure grid, a coronavirus disease 2019 airway bundle template was created using these simulations and clinical experiences for others to adapt to their sites. CONCLUSIONS: Integration of tabletop planning, in situ simulations, and debriefing of real coronavirus disease 2019 cases can enhance planning, training, job aids, and feasible policies/procedures that address human factors, team communication, equipment choice, and patient/provider safety in the coronavirus disease 2019 pandemic era.


title: Atypical Neurological Manifestations of COVID-19

text: The novel coronavirus (SARS-CoV-2), belonging to a group of RNA-enveloped viruses and believed to be transmitted by aerosol route, is a worldwide pandemic. Many studies have described typical clinical manifestations such as fever, cough, fatigue, diarrhea, and nasal congestion. However, to our knowledge, there are minimal studies on the neurological manifestations in SARS-CoV-2 positive patients. Our review aims to identify the various neurological manifestations in SARS-CoV-2 positive patients, which could be an added advantage in the early diagnosis and prevention of further complications of the nervous system.


title: Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients

text: BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.


title: Vox Sanguinis International Forum on Hospital Transfusion Services' Response to COVID‐19

text: The novel coronavirus (SARS‐Cov‐2) that was first reported in Wuhan, China and provokes the COVID‐19 disease has developed into a pandemic with hundreds of thousands of people infected. Many governments have enforced social isolation protocols on their citizens, which has led to the closure of many large public gatherings in order to limit the spread of the virus. These closures could reasonably be expected to affect blood collections, thereby presaging shortages of blood for transfusion. On the other hand, steps such as the postponement of elective surgeries and other non‐urgent transfusions could mitigate against potential shortfalls in the blood supply.


title: Conjunctivitis as a Sentinel of SARS-CoV-2 Infection: a Need of Revision for Mild Symptoms

text: COVID-19 has been declared a pandemic by the World Health Organization on March 11, and since then, more than 3 million cases and a quarter million deaths have occurred due to it. Lately, there is a growing evidence for an ophthalmologic symptom (conjunctivitis) to be connected with the disease. This seems to happen in early stages of the infection by SARS-CoV-2, and thus, it is of major importance to understand the mechanism through which the virus can facilitate such a symptom. Here, we are proposing a molecular mechanism through which the novel coronavirus could act in order to affect the eye and use it as another, secondary but alternative, point of entry to the host organism.


title: Human Bocavirus and Acute Wheezing in Children

text: Background. Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. Methods. We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays. Results. At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection. Conclusions. Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus.


title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management

text: As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.


title: COVID‐19 infection in solid organ transplant recipients: A single‐center experience with patients immediately after transplantation

text: In our transplant center, infection with SARS‐CoV‐2 virus was confirmed in 4 organ transplant recipients (3 kidney and 1 liver transplant recipients) during their early post‐transplant hospital stay. In this paper, we report the basic characteristics, management, clinical course, and outcomes of these patients.


title: Rapid diagnosis of gastrointestinal tract infections due to parasites, viruses, and bacteria

text: Abstract Rapid diagnostic techniques are valuable tools in the diagnosis of gastrointestinal infections, especially for the detection of some microorganisms and in certain groups of patients. While antigen detection techniques are widely used in Clinical Microbiology laboratories, for the diagnosis of viruses, some parasites and some bacteria, molecular techniques are routinely used only for some pathogens (such as Clostridium difficile). However, molecular techniques are constantly evolving, and they allow a rapid diagnosis for an increasing number of pathogens, with high sensitivity and specificity. In addition, they are also able to detect virulence factors or resistance mechanisms. Syndromic surveillance systems, which detect different pathogens simultaneously, are very promising because they enable the most frequent pathogens to be diagnosed in a few hours and they can be very useful in certain patients. For the diagnosis of Helicobacter pylori infection, molecular techniques are able to detect bacteria and its resistance to clarithromycin and levofloxacin, allowing the most appropriate treatment to be selected for each patient when bacterial culture is not possible.


title: Sleep problems among Chinese adolescents and young adults during the coronavirus-2019 pandemic

text: OBJECTIVE: To assess the prevalence and sociodemographic correlates of insomnia symptoms among Chinese adolescents and young adults affected by the outbreak of coronavirus disease-2019 (COVID-19). METHODS: This cross-sectional study included Chinese adolescents and young adults 12–29 years of age during part of the COVID-19 epidemic period. An online survey was used to collect demographic data, and to assess recognition of COVID-19, insomnia, depression, and anxiety symptoms using the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaires, respectively. The Social Support Rate Scale was used to assess social support. RESULTS: Among 11,835 adolescents and young adults included in the study, the prevalence of insomnia symptoms during part of the COVID-19 epidemic period was 23.2%. Binomial logistic regression analysis revealed that female sex and residing in the city were greater risk factors for insomnia symptoms. Depression or anxiety were risk factors for insomnia symptoms; however, social support, both subjective and objective, was protective factors against insomnia symptoms. Furthermore, anxiety and depression symptoms were mediators of social support and insomnia symptoms. CONCLUSIONS: Results of this study revealed a high prevalence of sleep problems among adolescents and young adults during the COVID-19 epidemic, especially senior high school and college students, which were negatively associated with students’ projections of trends in COVID-19. The adverse impact of COVID-19 was a risk factor for insomnia symptoms; as such, the government must devote more attention to sleep disorders in this patient population while combating COVID-19.


title: Zooming in to Westminster

text: One of BVA's key roles is informing parliamentarians about the issues affecting the veterinary profession and lobbying directly on behalf of members. In early June we organised a virtual Westminster briefing for MPs and Peers to bring them up to date with the impact of Covid-19 on vets across the UK.


title: COVID-19 kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests

text: AIMS: An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve. METHODS AND RESULTS: We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001). CONCLUSION: The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.


The saga continues: is COVID-19 a cardiopulmonary disease?


title: Genetic properties of endemic Chinese porcine epidemic diarrhea virus strains isolated since 2010

text: Acute diarrhea outbreaks caused by porcine epidemic diarrhea virus (PEDV) have been observed in various pig-breeding provinces of China since December 2010. Endemic strains of PEDV were isolated from different areas, and the complete genome sequences of 10 isolates were determined. Our objective in this study was to genetically characterize current Chinese field isolates of PEDV to better understand their epidemiology and genetic diversity. Sequence analysis showed that 10 post-2010 isolates shared high homology with each other and were always clustered together with the virulent DR13 strains (South Korea) and/or one earlier Chinese strain, CH-S, in phylogenetic analysis. All post-2010 isolates possessed common sequence changes in each gene. Our results suggest that current Chinese PEDV isolates originated from either South Korean and/or Chinese ancestors that underwent some genetic variation, thereby forming a new PEDV genotype in China.


title: Recent Advances of Vaccine Adjuvants for Infectious Diseases

text: Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.


title: Barriers to implementing antimicrobial stewardship programmes in three Saudi hospitals: Evidence from a qualitative study

text: Abstract Objectives This study explored antimicrobial stewardship programme (ASP) team members’ perspectives regarding factors influencing the adoption and implementation of these programmes in Saudi hospitals. Methods This was a qualitative study based on face-to-face semistructured interviews with healthcare professionals involved in ASPs and activities across three Ministry of Health (MoH) hospitals in Saudi Arabia (n = 18). Interviews were also conducted with two representatives of a General Directorate of Health Affairs in a Saudi region and two representatives of the Saudi MoH (n = 4) between January–February 2017. Results Despite the existence of a national strategy to implement ASPs in Saudi MoH hospitals, their adoption and implementation remains low. Hospitals have their own antimicrobial stewardship policies, but adherence to these is poor. ASP team members highlight that lack of enforcement of policies and guidelines from the MoH and hospital administration is a significant barrier to ASP adoption and implementation. Other barriers include disintegration of teams, poor communication, lack of recruitment/shortage of ASP team members, lack of education and training, and lack of health information technology (IT). Physicians’ fears and concerns in relation to liability are also a barrier to their adoption of ASPs. Conclusion This is the first qualitative study exploring barriers to ASP adoption and implementation in Saudi hospitals from the perspective of ASP team members. Formal endorsement of ASPs from the MoH as well as hospital enforcement of policies and provision of human and health IT resources would improve the adoption and implementation of ASPs in Saudi hospitals.


title: Safety and efficacy of amiodarone in a patient with COVID-19

text: Abstract There is an urgent need of effective treatments for COVID-19. Amiodarone, like hydroxychloroquine, exerts antiviral actions by interfering with endocytosis and viral replication. Here we report the first case of a patient affected by respiratory failure related to COVID-19, and recovering after only supportive measures and a short amiodarone course.


Hepatitis B: Prevalence, Hope


title: Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review

text: BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary


title: A rebuttal to the comments on the genome order index and the Z-curve

text: BACKGROUND: Elhaik, Graur and Josic recently commented on the genome order index (S) and the Z-curve (Elhaik et al. Biol Direct 2010, 5: 10). S is a quantity defined as S = a(2 )+ c(2 )+ g(2 )+ t(2), where a, c, g and t denote corresponding base frequencies. The Z-curve is a three dimensional curve that represents a DNA sequence in the manner that each can be uniquely reconstructed given the other. Elhaik et al. made 4 major claims. 1) In the previous mapping system with the regular tetrahedron, calculation of the radius of the inscribed sphere is "a mathematical error". 2) S follows an exponential distribution and is narrowly distributed with a range of (0.25 - 0.33). 3) Based on the Chargaff's second parity rule (PR2), "S is equivalent to H [Shannon entropy]" and they are derivable from each other. 4) Z-curve "suffers from over dimensionality", because based on the analysis of 235 bacterial genomes, x and y components contributed only less than 1% of the variance and therefore "would be of little use". RESULTS: 1) Elhaik et al. mistakenly neglected the parameter [Formula: see text] when calculating the radius of the inscribed sphere. 2) The exponential distribution of S is a restatement of our previous conclusion, and the range of (0.25 - 0.33) only paraphrases the previously suggested S range (0.25 -1/3). 3) Elhaik et al. incorrectly disregard deviations from PR2 by treating the deviations as 0 altogether, reduce S and H, both having 4 variables, a, c, g and t, into functions of one single variable, a only, and apply this treatment to all DNA sequences as the basis of their "demonstration", which is therefore invalid. 4) Elhaik et al. confuse numeral smallness with biological insignificance, and disregard the distributions of purine/pyrimidine and amino/keto bases (x and y components), the variations of which, although can be less than that of GC content, contain rich information that is important and useful, such as in locating replication origins of bacterial and archaeal genomes, and in studies of gene recognition in various species. CONCLUSION: Elhaik et al. confuse S (a single number) with Z-curve (a series of 3D coordinates), which are distinct. To use S as a case study of Z-curve, by itself, is invalid. S and H are neither equivalent nor derivable from each other. The criticisms of Elhaik, Graur and Josic are wrong. REVIEWERS: This article was reviewed by Erik van Nimwegen.


title: A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein

text: SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease—COVID-19— within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus’s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the “closed” prefusion S structure, but is accessible in “open” conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTS High resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.


title: Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020

text: PURPOSE: This ecological analysis investigates the spatial patterns of the COVID‐19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID‐19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state‐level measure of the percent of the population that has been tested for COVID‐19 was used to control for the impact of testing. FINDINGS: The impact of COVID‐19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID‐19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID‐19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to “shelter‐in‐place” should continue to stem the spread of COVID‐19.


Why coronavirus death rate is so hard to pin down


title: Protein co-expression network analysis (ProCoNA)

text: BACKGROUND: Biological networks are important for elucidating disease etiology due to their ability to model complex high dimensional data and biological systems. Proteomics provides a critical data source for such models, but currently lacks robust de novo methods for network construction, which could bring important insights in systems biology. RESULTS: We have evaluated the construction of network models using methods derived from weighted gene co-expression network analysis (WGCNA). We show that approximately scale-free peptide networks, composed of statistically significant modules, are feasible and biologically meaningful using two mouse lung experiments and one human plasma experiment. Within each network, peptides derived from the same protein are shown to have a statistically higher topological overlap and concordance in abundance, which is potentially important for inferring protein abundance. The module representatives, called eigenpeptides, correlate significantly with biological phenotypes. Furthermore, within modules, we find significant enrichment for biological function and known interactions (gene ontology and protein-protein interactions). CONCLUSIONS: Biological networks are important tools in the analysis of complex systems. In this paper we evaluate the application of weighted co-expression network analysis to quantitative proteomics data. Protein co-expression networks allow novel approaches for biological interpretation, quality control, inference of protein abundance, a framework for potentially resolving degenerate peptide-protein mappings, and a biomarker signature discovery.


title: Replication of an enteric bovine coronavirus in intestinal organ cultures

text: A coronavirus isolated in tracheal organ cultures from the faeces of a calf with diarrhoea readily multiplied on passage in intestinal organ cultures. Evidence for multiplication was obtained by the production of viral haemagglutinin in organ culture fluids and the presence of immunofluorescence and viral particles in the columnar epithelial cells of the villi. Thus virus multiplication was studiedin vitro in the cell type in which it multiplies naturally.


title: Oklahoma to provide iPads for telehealth during pandemic

text: The Oklahoma Department of Mental Health and Substance Abuse is taking action to help those feeling depressed while home during the coronavirus pandemic, News 9 reported. Starting April 10, every city‐county health department in the state will be equipped with an iPad. Someone walk‐ing in needing help can use the iPad to speak with a mental health professional. The person can take the iPad home with them to continue conversations with the provider. “There's a button on it. They hit the button and it links up to community mental health providers in their area. Someone is able to talk with them and work through it,” said Carrie Slatton‐Hodges, the interim commissioner for the department. Eighty‐one sites across the state will have the iPads. Because of the state's large presence of telehealth technology, Slatton‐Hodges said the department has been able to continue performing 90% of services.


title: Short term outcome and risk factors for mortality in adults with critical severe acute respiratory syndrome (SARS)

text: The independent risk factors to predict mortality of critical severe acute respiratory syndrome (SARS) were investigated. One hundred and two patients diagnosed with critical SARS were admitted to hospitals of Shanxi Province, from March 7, 2003 to June 4, 2003. The patients were prospectively studied after admission to access their short term outcomes and the risk factors associated with adverse outcomes, defined as death. All the demographic and clinical characteristics were studied and univariate and multivariate Logistic regression were employed to access the risk factors. The results showed that of the 102 cases, 23 patients died, with a crude mortality rate of 22.5%. Multivariate Logistic regression revealed that age above 50 [odds ratio (OR) 1. 10, 95% confidence internal (CI) 1.03 to 1.16,P=0.004], lymphopenia at early stage (OR 14.62, 95% CI 1.78 to 11.97,P=0.01) were independently associated with mortality. On the other side, psychotherapy (OR 0.01, 95% CI 0.00 to 0.06,P<0.001) was independently associated with aliveness. It was concluded that critical SARS is a new disease entity that carries significant mortality and morbidity. Specific clinical and laboratory parameters predicting unfavorable and favorable outcomes have been identified.


The role of a cytokine storm in severe COVID-19 disease in pregnancy


The sequence of cDNA of bovine coronavirus 32K nonstructural gene.


title: Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study

text: BACKGROUND: Although allergic asthma is a complex area with many interacting factors involved, the ‘hygiene hypothesis’ proposes that a lack of exposure to infection during childhood may polarise the immune system towards allergen-reactive Th2-type responses in genetically susceptible individuals. Toll-like receptors (TLRs) play a key role within the innate immune system and TLR7 agonists have previously been shown to up-regulate Th1 responses and down-regulate Th2 responses to allergens in murine models of allergic or chronic asthma. This study aimed to examine the efficacy and safety of the novel TRL7 agonist AZD8848, which has been developed as an antedrug. METHODS: In this double-blind, randomised, parallel-group study, AZD8848 60 μg or placebo was administered intranasally once-weekly for 8 weeks in patients with mild-to-moderate allergic asthma (NCT00999466). Efficacy assessments were performed at 1 and 4 weeks after the last dose. The primary outcome was the late asthmatic response (LAR) fall in forced expiratory volume in 1 s (FEV(1)) after allergen challenge at 1-week post-treatment. RESULTS: AZD8848 significantly reduced average LAR fall in FEV(1) by 27% vs. placebo at 1 week after treatment (p = 0.035). This effect was sustained at 4 weeks post-treatment; however, it did not reach clinical significance. AZD8848 reduced post-allergen challenge methacholine-induced airway hyper-responsiveness (AHR) vs. placebo at 1 week post-dosing (treatment ratio: 2.20, p = 0.024), with no effect at 4 weeks. There was no significant difference between the two groups in plasma cytokine, sputum Th2 cytokine or eosinophil responses post-allergen challenge at 1 week after treatment. The incidence of adverse events was similar in the two groups. AZD8848 was generally well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: In patients with allergic asthma, TLR7 agonists could potentially reduce allergen responsiveness by stimulating Type 1 interferon responses to down-regulate the dominant Th2 responses. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00999466.


title: Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron

text: RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined. Ideally, these RNA inhibitors should be expressed simultaneously from a single transgene transcript. In this study, we tested a multiplex microRNA (miRNA) expression strategy by inserting multiple effective anti-HIV siRNA sequences in the miRNA polycistron mir-17-92. Individual anti-HIV miRNAs that resemble the natural miRNA structures were optimized by varying the siRNA position in the hairpin stem to obtain maximal effectiveness against luciferase reporters and HIV-1. We show that an antiviral miRNA construct can have a greater intrinsic inhibitory activity than a conventional short hairpin (shRNA) construct. When combined in a polycistron setting, the silencing activity of an individual miRNA is strongly boosted. We demonstrate that HIV-1 replication can be efficiently inhibited by simultaneous expression of four antiviral siRNAs from the polycistronic miRNA transcript. These combined results indicate that a multiplex miRNA strategy may be a promising therapeutic approach to attack escape-prone viral pathogens.


title: Solving the COVID-19 Crisis in Post-Acute and Long-Term Care

text: Abstract Our nation’s nursing home industry has been in need of overhaul for decades – a situation made all the more evident by COVID-19. AMDA – The Society of Post-Acute and Long-Term Care Medicine is dedicated to quality in post-acute and long-term care (PALTC) process and outcomes. This special article presents five keys to solving the COVID-19 crisis in PALTC, related to policy, collaboration, individualization, leadership, and reorganization. Taking action during this crisis may prevent sinking back into the complacency and habits of our pre-COVID-19 lives.


title: Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay

text: BACKGROUND: Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. METHODS: Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). RESULTS: Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. CONCLUSIONS: DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the "PCR era", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.


Telehealth Policies Impacting Federally Qualified Health Centers in Face of COVID‐19


title: Stroke care in Europe during the COVID‐19 pandemic

text: In view of finite health care resources and the ethical principle of distributive justice, healthcare systems across Europe have been adapted to provide care for patients with coronavirus disease 2019 (COVID‐19) while not neglecting other serious medical emergencies. Policies to contain disease spreading and to preserve usual health care systems as much as possible differ considerably between countries.


docid: wcoydhvp

title: Barrier Shields: Not Just for Intubations in Today’s COVID-19 World?


Be Prepared


title: Computational Comparison and Visualization of Viruses in the Perspective of Clinical Information

text: This paper addresses the visualization of complex information using multidimensional scaling (MDS). MDS is a technique adopted for processing data with multiple features scattered in high-dimensional spaces. For illustrating the proposed techniques, the case of viral diseases is considered. The study evaluates the characteristics of 21 viruses in the perspective of clinical information. Several new schemes are proposed for improving the visualization of the MDS charts. The results follow standard clinical practice, proving that the method represents a valuable tool to study a large number of viruses.


title: TMPRSS2 and MSPL Facilitate Trypsin-Independent Porcine Epidemic Diarrhea Virus Replication in Vero Cells

text: Type II transmembrane serine proteases (TTSPs) facilitate the spread and replication of viruses such as influenza and human coronaviruses, although it remains unclear whether TTSPs play a role in the progression of animal coronavirus infections, such as that by porcine epidemic diarrhea virus (PEDV). In this study, TTSPs including TMPRSS2, HAT, DESC1, and MSPL were tested for their ability to facilitate PEDV replication in Vero cells. Our results showed that TMPRSS2 and MSPL played significant roles in the stages of cell–cell fusion and virus–cell fusion, whereas HAT and DESC1 exhibited weaker effects. This activation may be involved in the interaction between TTSPs and the PEDV S protein, as the S protein extensively co-localized with TMPRSS2 and MSPL and could be cleaved by co-expression with TMPRSS2 or MSPL. Moreover, the use of Vero cells expressing TMPRSS2 and MSPL facilitated PEDV replication in the absence of exogenous trypsin. In sum, we identified two host proteases, TMPRSS2 and MSPL, which may provide insights and a novel method for enhancing viral titers, expanding virus production, and improving the adaptability of PEDV isolates in vitro.


title: Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial

text: OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Vitamin A 25,000 IU daily. Vitamin D 600,000 IU once during study. Vitamin E 300 IU twice daily. Vitamin C is taken four times per day. B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B(2) 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B(6) 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg]. The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI. 2. Severity of pulmonary involvement according to CT scan. 3. Respiratory support (invasive or non-invasive). 4. Percentage of oxygen saturation (SpO2 level). 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α. 6. The patient’s body temperature. 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys). 8. Duration of hospitalization. 9. Mortality rate. RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1. Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).


title: Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage

text: Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy.


title: Prevalence and molecular characterization of infectious bronchitis virus isolated from chicken in Bangladesh

text: AIM: The present study was aimed to determine the prevalence of infectious bronchitis virus (IBV) as well as virus isolation, identification, and molecular characterization of various strains circulating in Bangladesh. MATERIALS AND METHODS: A total of 371 swabs and organ samples were collected from four types of chicken including layer, Sonali (local), broiler, and broiler breeder under eight districts (Rangpur, Bogura, Tangail, Dhaka, Gazipur, Mymensingh, Jamalpur, and Cumilla) during 2014-2016 in Bangladesh. RESULTS: Out of 371 samples, 65 samples were positive in reverse transcriptase polymerase chain reaction (RT-PCR) for molecular identification of IBV. The overall prevalence was 17.52% recorded and among the selected types of chicken, the highest prevalence of IBV was found in layer that was 42.22% followed by 17.24% in Sonali, 14.93% in broiler breeder, and lowest prevalence was 11.94% in broiler chicken, respectively. Moreover, the prevalence of IBV was recorded highest in aged chicken at 41-60 weeks, which was 54.55% in layer, 27.27% in Sonali, and, afterward, 14.68% was found in broiler breeder, respectively. Frequency of IBV more frequently in winter (22.67%) followed by rainy (15.87%) and summer season (11.58%). The highest prevalence of IBV was found Tangail district (41.67%) followed by Mymensingh (24.42%), Gazipur (19.32%), Dhaka (15.38%), Jamalpur (16.67%), Bogura (13.68%), Cumilla (5.88%), and Rangpur (9.26%), respectively. Samples that were found high positive in IBV RT-PCR (Ct value below 30) were subjected to inoculation into chicken egg embryo to observe characteristic changes in chicken embryo. Swabs and organ samples were processed and passaged in 9-day-old embryonated chicken eggs through allantoic cavity route. IBV virus suspected samples inoculated into chicken egg embryos after 3-5 passages showed dwarfing and curling of the embryos which are characteristic lesions of IBV. Allantoic fluid was collected from all inoculated eggs and performed partial sequencing of S1 gene for three isolates. After sequencing, the phylogenetic tree was constructed from the nucleotide sequences of IBV isolates. Two of the isolates are 4/91 IBV and another one matched with QX-like IBV. CONCLUSION: The results revealed that the three isolates from different places in Bangladesh were identified for the 1(st) time as which will help for IBV control strategy.


title: Diabetes and severity of COVID-19: what is the link?

text: In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.


title: Kawasaki syndrome and concurrent Coxsackie virus B3 infection

text: We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.


title: Of plagues, planes and politics: Controlling the global spread of infectious diseases by air

text: Abstract In recent years, the implications of globalisation for the spread of infectious diseases has begun to emerge as an area of concern to political geographers. Unsurprisingly, much of the contemporary literature focuses on the multifarious threats posed by human and, increasingly, non-human mobility. Prompted by current geopolitical concerns surrounding the public health implications of regular international air travel, this paper extends such research by exploring the ways in which the technology of the aeroplane stimulated the production of new international sanitary initiatives aimed at safeguarding global public health in an era of mass aeromobility. By tracing the development of sanitary regulations for aerial navigation, from their origins in the 1920s through the twentieth century in particular, we document the emergence of a series of public health interventions that were designed to limit the public health threat associated with increased international air travel and the concomitant rise in the mobility of infectious diseases. From inoculation certificates to quarantine and the routine ‘disinsection’ of passenger aircraft with powerful insecticides, modern air travel is replete with a complex set of procedures designed to lessen the risks associated with flying between different climatic and ecological zones. Our detailed examination of the historical context in which these procedures were devised and implemented leads us to consider the importance of time and space, power and efficacy, to the development of a more nuanced understanding of the shifting public health response to an increasingly fluid, mobile, and inter-connected society.


title: SARS-CoV2 coronavirus: So far polite with children. Debatable immunological and non-immunological evidence

text: Abstract The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS- CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


title: Dendritic Cells

text: Abstract T cells are an essential element that regulates the balance in immunity, by killing infected cells, helping antibody formation and suppressing autoimmune responses. However, T cells are incapable of recognizing native antigens. Instead, they recognize processed peptides presented by MHC molecules. Dendritic cells (DCs) are professional antigen presenting cells that inform the fight against invasive pathogens while enforcing tolerance to self and harmless environmental antigens. They capture pathogens and receive signals from pathogens that influence the outcome of immune responses. On the basis of these signals, DCs orchestrate antigen specific T cell differentiation. Alternatively they can silence self-reactive T cells by inducing deletion, anergy or regulation (Treg). This article will discuss the discovery, function and development of DCs and the mechanisms by which they link innate immunity to adaptive immunity.


title: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review

text: BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O’Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors’ affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus’ origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.