title: The Origin and Prevention of Pandemics

text: Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change and communication strategies. Since there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.


title: Informing emergency care for COVID‐19 patients: The COVID‐19 Emergency Department Quality Improvement Project protocol

text: Objectives: There is an urgency to support Australian ED clinicians with real‐time tools as the COVID‐19 pandemic evolves. The COVID‐19 Emergency Department (COVED) Quality Improvement Project has commenced and will provide flexible and responsive clinical tools to determine the predictors of key ED‐relevant clinical outcomes. Methods: The COVED Project includes all adult patients presenting to a participating ED and meeting contemporary testing criteria for COVID‐19. The dataset has been embedded in the electronic medical record and the COVED Registry has been developed. Results: Outcomes measured include being COVID‐19 positive and requiring intensive respiratory support. Regression methodology will be used to generate clinical prediction tools. Conclusion: This project will support EDs during this pandemic.


Treatment options for patients with HR+/HER2− advanced breast cancer during the COVID-19 pandemic: dose reduction of ribociclib does not diminish efficacy


title: The impact of COVID-19 on African American communities in the United States

text: IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.


title: Thrombosis risk associated with COVID-19 infection. A scoping review

text: BACKGROUND: Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging. METHODS: We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services. RESULTS: Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although and increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known. DISCUSSION: A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.


title: Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Causing a COVID-19 Case in Morocco

text: Here, we report a complete genome sequence obtained for a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from a nasopharyngeal swab specimen of a Moroccan patient with coronavirus disease 2019 (COVID-19).


title: Structural and operational redesigning of patient-centered ambulatory care pharmacy services and its effectiveness during the COVID-19 pandemic

text: BACKGROUND: The newly emerged coronavirus pandemic (COVID-19) has collapsed the entire global health care system. Due to these settings, a lot of strategic changes are adopted by healthcare facilities to ensure continuity in patient-centered services. OBJECTIVE: This study aims to evaluate the effectiveness of structural and operational changes made in ambulatory care pharmacy services during the COVID-19 pandemic. METHODS: A retrospective comparative study was conducted to evaluate the impact and effectiveness of patient-centered interventions and consequent access to medication management care within Johns Hopkins Aramco Health Care ambulatory care pharmacy services during the COVID-19 pandemic by comparing patient-centered key performance indicators before and during COVID-19 pandemic for a total of 4 months. RESULTS: As a result of the structural and operational changes made in patient-centered ambulatory care pharmacy services during the COVID-19 pandemic, a 48% prescriptions requests and 90% prescriptions fills are increased through online health portal application. A three-fold increase in the pharmacy call center utilization resulted in around 10% abandoned calls. In the number of physical visits to ambulatory care pharmacies, a 37% reduction was also noted. The decrease in staff schedule efficiency and an increase in average prescription waiting time were also noticed. The prescription collection through remote area pick up locations, and medication home delivery services were successful during COVID-19 pandemic as supported by statistical data. CONCLUSION: The access to ambulatory care pharmacy services during COVID-19 pandemic has been successfully maintained via medication home delivery, remote area pickup locations, pharmacy call-center consultations and refill requests, online health portal application services, and other measures, while reducing the number of physical visits to the JHAH hospital/clinic to ensure compliance with infection control and prevention measures.


title: Synthesizing data and models for the spread of MERS-CoV, 2013: key role of index cases and hospital transmission

text: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April-October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and distinguishes transmission by zoonotic (index) cases and secondary cases. When observation bias is assumed to account for the fact that all reported zoonotic cases are severe, but only ~57% of secondary cases are symptomatic, the average reproduction number of MERS-CoV is estimated to be 0.45 (95%CI:0.29–0.61). Alternatively, if these epidemiological observations are taken at face value, index cases are estimated to transmit substantially more effectively than secondary cases, (R(i) =0.84 (0.58–1.20) vs R(s)=0.36 (0.24–0.51)). In both scenarios the relative contribution of hospital-based transmission is over four times higher than that of community transmission, indicating that disease control should be focused on hospitalized patients. Adjusting previously published estimates for observation bias confirms a strong support for the average R < 1 in the first stage of the outbreak in 2013 and thus, transmissibility of secondary cases of MERS-CoV remained well below the epidemic threshold. More information on the observation process is needed to clarify whether MERS-CoV is intrinsically weakly transmissible between people or whether existing control measures have contributed meaningfully to reducing the transmissibility of secondary cases. Our results could help evaluate the progression of MERS-CoV in recent months in response to changes in disease surveillance, control interventions, or viral adaptation.


title: Molecular chaperones: from proteostasis to pathogenesis

text: Maintaining protein homeostasis (proteostasis) is essential for a functional proteome. A wide range of extrinsic and intrinsic factors perturb proteostasis, causing protein misfolding, misassembly, and aggregation. This compromises cellular integrity and leads to aging and disease, including neurodegeneration and cancer. At the cellular level, protein aggregation is counteracted by powerful mechanisms comprising of a cascade of enzymes and chaperones that operate in a coordinated multistep manner to sense, prevent, and/or dispose of aberrant proteins. Although these processes are well understood for soluble proteins, there is a major gap in our understanding of how cells handle misfolded or aggregated membrane proteins. This article provides an overview of cellular proteostasis with emphasis on membrane protein substrates and suggests host–virus interaction as a tool to clarify outstanding questions in proteostasis.


The Ethical Governance of the Digital During and After the COVID-19 Pandemic


title: Recombinase polymerase amplification: Basics, applications and recent advances

text: Abstract Recombinase polymerase amplification (RPA) is a highly sensitive and selective isothermal amplification technique, operating at 37–42°C, with minimal sample preparation and capable of amplifying as low as 1–10 DNA target copies in less than 20 min. It has been used to amplify diverse targets, including RNA, miRNA, ssDNA and dsDNA from a wide variety of organisms and samples. An ever increasing number of publications detailing the use of RPA are appearing and amplification has been carried out in solution phase, solid phase as well as in a bridge amplification format. Furthermore, RPA has been successfully integrated with different detection strategies, from end-point lateral flow strips to real-time fluorescent detection amongst others. This review focuses on the different methodologies and advances related to RPA technology, as well as highlighting some of the advantages and drawbacks of the technique.


title: Coagulopathy of Coronavirus Disease 2019

text: Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.” STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.


title: Crisis Decision Making on a Global Scale: Transition from Cognition to Collective Action under Threat of COVID‐19

text: This essay examines basic functions of crisis decision-making—cognition, communication, coordination, and control—in response to COVID-19. This crisis decision-making framework is applied to cases from South Korea, Italy, and the United States as public officials grapple with how to recognize, respond, and recover from this deadly, invisible threat. The authors acknowledge the harsh trade-off between the compelling need to limit transmission of the virus to protect public health and the consequent economic losses of halting social interaction. They draw implications from this crisis for better decision-making and investment in a global information infrastructure system to manage large-scale, multidisciplinary threats to the health, economy, and sustainability of the world's community of nations. The essay concludes that collective cognition, amplified by timely, valid communication and supported by sound planning, trained personnel, appropriate technology, and bold leadership, enables coordinated action needed to bring a large-scale global crisis under control. Evidence for Practice_ Invest in information technology to manage systematic data collection, analysis, and modeling. Provide timely, informed updates on community status to constituents. Maintain a knowledge base of resources, vulnerabilities, and plans.


title: Importance of SARS-CoV Spike Protein Trp-rich Region in Viral Infectivity

text: SARS-CoV entry is mediated by spike glycoprotein. During the viral and host cellular membrane fusion, HR1 and HR2 form 6-helix bundle, positioning the fusion peptide closely to the C-terminal region of ectodomain to drive apposition and subsequent membrane fusion. Connecting to the HR2 region is a Trp-rich region which is absolutely conserved in members of coronaviruses. To investigate the importance of Trp-rich region in SARS-CoV entry, we produced different mutated S proteins using Alanine scan strategy. SARS-CoV pseudotyped with mutated S protein was used to measure viral infectivity. To restore the aromaticity of Ala-mutants, we performed rescue experiments using phenylalanine substitutions. Our results show that individually-substituted Ala-mutants substantially decrease infectivity by >90%, global Ala-mutants totally abrogated infectivity. In contrast, Phe-substituted mutants are able to restore 10–25% infectivity comparing to the wild type. The results suggest that the Trp-rich region of S protein is essential for SARS-CoV infectivity.


title: Development of recombinant rabies viruses vectors with Gaussia luciferase reporter based on Chinese vaccine strain CTN181

text: Abstract The recombinant rabies virus (RV) vectors encoding the secreted gene marker Gaussia luciferase (Gluc) were generated based on Chinese vaccine strain CTN181. Vectors included replication competent CTN-Gluc, CTN/GQ333R-Gluc, in which the amino acid in position 333 of glycoprotein was mutated from glutamine (Q) to arginine (R), and replication constrained CTNΔG-Gluc, in which the glycoprotein encoding gene (G) was deleted. The growth of recombinant RVs in transfected cells was confirmed through biochemical assays of Gluc activities. Gluc expression in recombinant CTNΔG-Gluc virus was highest while that in CTN/GQ333R-Gluc virus was lowest. The optimal time to harvest recombinant RVs was determined and the function of pathogenic and nonpathogenic rabies glycoprotein in virus recovery was examined. The addition of glycoprotein was slightly beneficial for virus recovery and the titer of rescued virus was lowered even when the amino acid in G333 position of glycoprotein was mutated from nonpathogenic Gln to pathogenic Arg. Conclusions: Viral vectors based on a human rabies vaccine strain CTN181 were successful. Gluc was useful as an in vitro gene marker for monitoring the growth of recombinant RVs iteratively in cell culture.


title: Analysis of Epidemiological and Clinical features in older patients with Corona Virus Disease 2019 (COVID-19) out of Wuhan

text: BACKGROUND: The outbreak of COVID-19 has become a big threat to China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 out of Wuhan. METHODS: A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from Jan 17 to Feb 12, 2020. Epidemiological, clinical and treatment data were analyzed between those older (≥60y) and younger (<60y) patients. RESULTS: Total 788 patients with confirmed COVID-19 were selected, where 136 were older patients with corresponding age of 68.28y±7.314y. There was a significantly higher frequency of women in the older patients compared with the younger patients (57.35% vs 46.47%, P=0.021). The presence of coexisting medical condition was significantly higher in older patients compared with younger patients (55.15% vs 21.93%, P<0.001), including the rate of hypertension, diabetes, heart diseases and COPD. Significantly higher rates of severe (older vs younger groups: 16.18% vs 5.98%, P<0.001)/critical (8.82% vs 0.77%, P<0.001) type, shortness of breath (12.50% vs 3.07%, P<0.001) and high temperature of >39.0℃ (13.97% vs 7.21%, P=0.010) were observed in older patients compared with younger patients. Finally, Higher rates of ICU admission (9.56% vs 1.38%, P<0.001) and methylprednisolone application (28.68% vs 9.36%, P<0.001) were also identified in older patients. CONCLUSIONS: The specific epidemiological and clinical features of older COVID-19 patients included significantly higher female gender, body temperature, co-existing of basic diseases and rate of severe and critical type.


Comment on: “To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out. Characterization of herpetic lesions in hospitalized COVID-19 patients.”


title: Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD

text: This consensus statement established under the auspices of the German working group on BM and blood stem cell transplantation (DAG-KBT), the German Society of Hematology and Oncology (DGHO), the Austrian Stem Cell Transplant Working Group, the Swiss Blood Stem Cell Transplantation Group (SBST) and the German-Austrian Pediatric Working Group on SCT (Päd-Ag-KBT) summarizes current evidence for diagnosis, immunosuppressive and supportive therapy to provide practical guidelines for the care and treatment of patients with pulmonary manifestations of chronic GVHD (cGVHD). Pulmonary cGVHD can present with obstructive and/or restrictive changes. Disease severity ranges from subclinical pulmonary function test (PFT) impairment to respiratory insufficiency with bronchiolitis obliterans being the only pulmonary complication currently considered diagnostic of cGVHD. Early diagnosis may improve clinical outcome, and regular post-transplant follow-up PFTs are recommended. Diagnostic work-up includes high-resolution computed tomography, bronchoalveolar lavage and histology. Topical treatment is based on inhalative steroids plus beta-agonists. Early addition of azithromycin is suggested. Systemic first-line treatment consists of corticosteroids plus, if any, continuation of other immunosuppressive therapy. Second-line therapy and beyond includes extracorporeal photopheresis, mammalian target of rapamycin inhibitors, mycophenolate, etanercept, imatinib and TLI, but efficacy is limited. Clinical trials are urgently needed to improve understanding and treatment of this deleterious complication.


title: Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers

text: We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.


title: Direct multiplexed whole genome sequencing of respiratory tract samples reveals full viral genomic information

text: Abstract Background Acute respiratory tract infections (RTI) cause substantial morbidity during childhood, and are responsible for the majority of pediatric infectious diseases. Although most acute RTI are thought to be of viral origin, viral etiology is still unknown in a significant number of cases. Objectives Multiplexed whole genome sequencing (WGS) was used for virome determination directly on clinical samples as proof of principle for the use of deep sequencing techniques in clinical diagnosis of viral infections. Study design WGS was performed with nucleic acids from sputum and nasopharyngeal aspirates from four pediatric patients with known respiratory tract infections (two patients with human rhinovirus, one patient with human metapneumovirus and one patient with respiratory syncytial virus), and from four pediatric patients with PCR-negative RTI, and two control samples. Results Viral infections detected by routine molecular diagnostic methods were confirmed by WGS; in addition, typing information of the different viruses was generated. In three out of four samples from pediatric patients with PCR-negative respiratory tract infections and the two control samples, no causative viral pathogens could be detected. In one sample from a patient with PCR-negative RTI, rhinovirus type-C was detected. Almost complete viral genomes could be assembled and in all cases virus species could be determined. Conclusions Our study shows that, in a single run, viral pathogens can be detected and characterized, providing information for clinical assessment and epidemiological studies. We conclude that WGS is a powerful tool in clinical virology that delivers comprehensive information on the viral content of clinical samples.


title: Protective and pathogenic roles for mast cells during viral infections

text: Mast cells (MCs) are long-lived immune cells. They are armed with preformed mediators within granules that can be instantaneously released in response to an invading pathogen, including certain viruses. At the skin and mucosae, they initiate innate immune responses and promote the development of adaptive immune responses, through cellular recruitment or antigen presentation. However, systemic MC activation may promote immune pathologies through their vasoactive proteases and biogenic amines. Recently, MC products were identified to contribute to pathologies associated with viral hemorrhagic fever, such vascular leakage and thrombocytopenia. Similar associations of MCs with disease severity have been noted for certain respiratory viral pathogens. Here we discuss the specific MC responses to viruses and their influences on functional immune outcomes during infection.


title: Replication kinetics of different porcine circovirus 2 strains in PK-15 cells, fetal cardiomyocytes and macrophages

text: In this in vitro study, the replication kinetics of porcine circovirus type 2 (PCV2) in porcine alveolar macrophages (PAM) and fetal cardiomyocytes (FCM), two target cells in vivo, was compared with that in PK-15 cells. Cultures were inoculated with either the postweaning multisystemic wasting syndrome (PMWS)-associated strain Stoon-1010 or the abortion-associated strain 1121. Viral proteins were visualized and virus production was determined. In PK-15 cells, the capsid protein was expressed between 6 and 12 hours post inoculation (hpi), it relocated to the nucleus between 12 and 24 hpi. At that time, Rep protein was also detected in the nucleus. This sequence of events also occurred in FCM and PAM but nuclear localized antigens appeared later (48 hpi) and in a lower percentage of cells. In PAM, clear differences in susceptibility were seen between pigs. In PAM from two out of five tested pigs, nuclear localized antigens were not detected, whereas in PAM from three other pigs they were seen in up to 20% of the antigen-positive cells. Virus production was observed in PK-15 but not in PAM or FCM cultures. In a second study, the replication kinetics of seven different PCV2 strains were compared in PK-15 cells. It was shown that the two abortion-associated strains had a different replication kinetics in comparison with PMWS or porcine dermatitis and nephropathy syndrome associated strains. With the abortion-associated strains, a higher number of infected cells was observed at 24 hpi and the percentage of infected cells with nuclear localised antigens was lower compared to that of other strains.


title: Retained copper fragments following removal of a copper intrauterine device: Two case reports

text: Abstract Intrauterine devices (IUDs) are safe, cost-effective, and reliable contraceptives, and are gaining popularity worldwide. While complications associated with IUD use are rare, they range from expulsion to uterine perforation. Numerous reports have been published regarding the sequelae of intraperitoneal copper IUDs or retained fragments following the removal of a fractured device. No data exist, however, on the intraperitoneal retention of copper following the removal of an otherwise intact IUD. Here we present two patients in whom copper IUDs were found to have missing fragments of copper wire despite removal of an otherwise intact IUD found in utero. We caution providers to examine all removed devices carefully, to surgically address intraperitoneal copper in order to mitigate adhesion formation, and to counsel patients about this potentially serious complication.


title: Bilan français des effets indésirables du vaccin Prévenar 13®

text: Résumé Objectif Décrire le profil et l’incidence des effets indésirables (EI) notifiés avec Prévenar 13® depuis sa commercialisation. Méthode Analyse de tous les effets indésirables notifiés en France entre le 1er juillet 2010 et le 31 octobre 2014. Résultats En 4 ans et 4 mois, 376 déclarations d’EI dont 252 graves (67 %) ont été enregistrées, parmi lesquels 83 étaient survenus au décours d’une injection de Prévenar 13® seul. Il s’agissait de 39 EI cutanés et 16 neurologiques, de 4 malaises, de 9 fièvres et d’une thrombopénie. L’évolution a été favorable pour 88 % des EI graves et aucun des 12 décès rapportés n’a été attribué à un EI de la vaccination. Cinquante-neuf cas d’infection pneumococcique faisant suspecter une inefficacité vaccinale ont été rapportés, mais seuls 16 ont pu être considérés comme un réel échec de la vaccination. Discussion Dans de nombreux cas, le Prévenar 13® avait été administré le même jour qu’un vaccin hexavalent avec lequel l’EI rapporté était attendu. Le profil des EI rapportés au décours de l’injection de Prévenar 13® seul est similaire à celui observé avec le Prévenar 7®. Conclusion Le suivi de pharmacovigilance de Prévenar 13® mis en place en France depuis sa commercialisation en 2010 et qui porte à ce jour sur plus de 11 800 000 doses distribuées n’a pas mis en évidence de fait nouveau de sécurité. Summary Objective To describe the profile and the incidence of adverse events (AEs) reported with Prevenar 13® since its commercialization. Method Analysis of all adverse events reported with Prevenar 13® in France between 1st July 2010 and 31 October 2014. Results In 4 years and 4 months, 376 AEs, including 252 severe (67%), were recorded, 83 of which occurred following an injection of Prevenar 13® alone: 39 cutaneous AEs, 16 neurological AEs, four cases of collapse or shock, nine cases of fever, and one of thrombocytopenia. For the serious AEs, the outcome was favorable in 88% of cases and none of the 12 reported deaths were attributed to a side effect of vaccination. Fifty-nine cases of pneumococcal disease that suggest an ineffective vaccine were reported, but only 16 can be considered as a real failure of the vaccination. Discussion In many cases, Prevenar 13® was administered on the same day as a hexavalent vaccine with which the AEs reported were expected. The profile of AEs reported following Prevenar 13® alone is similar to that seen with Prevenar 7®. Conclusion Since its release in 2010, the Prevenar 13® pharmacovigilance survey, which includes more than 11,800,000 distributed doses, did not show any new information in terms of tolerance safety.


The Role of Oral and Maxillofacial Surgeons in COVID-19 Response


title: Efficiency analysis of major cruise lines

text: Three major cruise lines account for 82% of the total market share. Their financial statements show different results between the operating incomes and net incomes over time. To examine the major causes of the differences, this study measured the efficiency of the top three cruise lines to develop a network DEA model to analyze the cruise operations at two stages, namely operating and non-operating stages. In addition, the determinants of the efficiencies were examined using a bootstrapped-truncated regression model. Overall, cruise lines were efficient at the operating stage, but varied widely in the efficiency of the non-operating stage. Cruise lines attempting high capacity expansion were relatively inefficient because of the heavy interest payments arising from the high debt-to-capital ratio. Moreover, the neglected hedging policy regarding the financial risks also contributed to the inefficiency.


title: A global needs assessment in times of a global crisis: world psychiatry response to the COVID-19 pandemic

text: The COVID-19 pandemic has stunned the global community with marked social and psychological ramifications. There are key challenges for psychiatry that require urgent attention to ensure mental health well-being for all – COVID-19-positive patients, healthcare professionals, first responders, people with psychiatric disorders and the general population. This editorial outlines some of these challenges and research questions, and serves as a preliminary framework of what needs to be addressed. Mental healthcare should be an integral component of healthcare policy and practice towards COVID-19. Collaborative efforts from psychiatric organisations and their members are required to maximise appropriate clinical and educational interventions while minimising stigma.


title: High‐Performance Virus Removal Filter Paper for Drinking Water Purification

text: Access to drinking water is one of the greatest global challenges today. In this study, the virus removal properties of mille‐feuille nanocellulose‐based filter papers of varying thicknesses from simulated waste water (SWW) matrix are evaluated for drinking water purification applications. Filtrations of standard SWW dispersions at various total suspended solid (TSS) content are performed, including spiking tests with 30 nm surrogate latex particles and 28 nm ΦX174 bacteriophages. Filter papers of thicknesses 9 and 29 µm are used, and the filtrations are performed at two different operational pressures, i.e., 1 and 3 bar. The presented data using SWW matrix show, for the first time, that a filter paper made from 100% nanocellulose has the capacity to efficiently remove even the smallest viruses, i.e., up to 99.9980–99.9995% efficiency, at industrially relevant flow rates, i.e., 60–500 L m(−2) h(−1), and low fouling, i.e., V (max) > 10(3)–10(4) L m(−2). The filter paper presented in this work shows great promise for the development of robust, affordable, and sustainable water purification systems.


Approach to upper GastroIntestinal cancer surgery during the COVID-19 pandemic – Experience from a UK cancer centre


title: Complex Reporting of the COVID-19 Epidemic in the Czech Republic: Use of an Interactive Web-Based App in Practice

text: BACKGROUND: The beginning of the coronavirus disease (COVID-19) epidemic dates back to December 31, 2019, when the first cases were reported in the People’s Republic of China. In the Czech Republic, the first three cases of infection with the novel coronavirus were confirmed on March 1, 2020. The joint effort of state authorities and researchers gave rise to a unique team, which combines methodical knowledge of real-world processes with the know-how needed for effective processing, analysis, and online visualization of data. OBJECTIVE: Due to an urgent need for a tool that presents important reports based on valid data sources, a team of government experts and researchers focused on the design and development of a web app intended to provide a regularly updated overview of COVID-19 epidemiology in the Czech Republic to the general population. METHODS: The cross-industry standard process for data mining model was chosen for the complex solution of analytical processing and visualization of data that provides validated information on the COVID-19 epidemic across the Czech Republic. Great emphasis was put on the understanding and a correct implementation of all six steps (business understanding, data understanding, data preparation, modelling, evaluation, and deployment) needed in the process, including the infrastructure of a nationwide information system; the methodological setting of communication channels between all involved stakeholders; and data collection, processing, analysis, validation, and visualization. RESULTS: The web-based overview of the current spread of COVID-19 in the Czech Republic has been developed as an online platform providing a set of outputs in the form of tables, graphs, and maps intended for the general public. On March 12, 2020, the first version of the web portal, containing fourteen overviews divided into five topical sections, was released. The web portal’s primary objective is to publish a well-arranged visualization and clear explanation of basic information consisting of the overall numbers of performed tests, confirmed cases of COVID-19, COVID-19-related deaths, the daily and cumulative overviews of people with a positive COVID-19 case, performed tests, location and country of infection of people with a positive COVID-19 case, hospitalizations of patients with COVID-19, and distribution of personal protective equipment. CONCLUSIONS: The online interactive overview of the current spread of COVID-19 in the Czech Republic was launched on March 11, 2020, and has immediately become the primary communication channel employed by the health care sector to present the current situation regarding the COVID-19 epidemic. This complex reporting of the COVID-19 epidemic in the Czech Republic also shows an effective way to interconnect knowledge held by various specialists, such as regional and national methodology experts (who report positive cases of the disease on a daily basis), with knowledge held by developers of central registries, analysts, developers of web apps, and leaders in the health care sector.


title: Discovery of DNA Viruses in Wild-Caught Mosquitoes Using Small RNA High throughput Sequencing

text: BACKGROUND: Mosquito-borne infectious diseases pose a severe threat to public health in many areas of the world. Current methods for pathogen detection and surveillance are usually dependent on prior knowledge of the etiologic agents involved. Hence, efficient approaches are required for screening wild mosquito populations to detect known and unknown pathogens. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the use of Next Generation Sequencing to identify viral agents in wild-caught mosquitoes. We extracted total RNA from different mosquito species from South China. Small 18–30 bp length RNA molecules were purified, reverse-transcribed into cDNA and sequenced using Illumina GAIIx instrumentation. Bioinformatic analyses to identify putative viral agents were conducted and the results confirmed by PCR. We identified a non-enveloped single-stranded DNA densovirus in the wild-caught Culex pipiens molestus mosquitoes. The majority of the viral transcripts (.>80% of the region) were covered by the small viral RNAs, with a few peaks of very high coverage obtained. The +/− strand sequence ratio of the small RNAs was approximately 7∶1, indicating that the molecules were mainly derived from the viral RNA transcripts. The small viral RNAs overlapped, enabling contig assembly of the viral genome sequence. We identified some small RNAs in the reverse repeat regions of the viral 5′- and 3′ -untranslated regions where no transcripts were expected. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate for the first time that high throughput sequencing of small RNA is feasible for identifying viral agents in wild-caught mosquitoes. Our results show that it is possible to detect DNA viruses by sequencing the small RNAs obtained from insects, although the underlying mechanism of small viral RNA biogenesis is unclear. Our data and those of other researchers show that high throughput small RNA sequencing can be used for pathogen surveillance in wild mosquito vectors.


title: Characterization of the interaction between recombinant porcine aminopeptidase N and spike glycoprotein of porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhea (PED) has caused huge economic losses to the global pork industry. Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). Interestingly, some recent studies have indicated that pAPN is not a functional receptor for PEDV. To date, there is a lack of a direct evidence for the interaction between pAPN and PEDV S protein in vitro. Here, we prepared pAPN ectodomain and the truncated variants of PEDV S protein in Drosophila S2 cells. These recombinant proteins were homogeneous after purification by metal-affinity and size-exclusion chromatography. We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Finally, we characterized their interactions by gel filtration chromatography, native-polyacrylamide gel electrophoresis (PAGE) and surface plasmon resonance (SPR) analyses. The results showed that their affinities were too low to form complexes, which suggest that pAPN may be controversial as the genuine receptor for PEDV. Therefore, further research needs to be carried out to elucidate the interaction between PEDV and its genuine receptor.


title: Isolation and characterization of a new porcine epidemic diarrhea virus variant that occurred in Korea in 2014

text: Outbreaks of porcine epidemic diarrhea (PED) have resulted in significant economic losses in the swine industry, and another PED outbreak occurred in 2014 in Korea. Isolating and culturing PED virus (PEDV) allow investigations into its pathogenesis and the development of vaccines and diagnostic assays. In this study, we successfully isolated two PEDV isolates (QIAP1401 and QIAP1402) from naturally infected piglets at Jeju-do, Korea. Viral propagation was confirmed in Vero cells based on cytopathic effect, immunofluorescence assay, reverse transcription-polymerase chain reaction, and electron microscopic analyses. The QIAP401 isolate propagated well in Vero cells for 70 passages, with titers of 10(6.5) to 10(7.0) 50% tissue culture infectious dose/mL, which increased gradually with passaging. The nucleotide and amino acid sequences of the QIAP1401 isolate were determined and compared with those of other PEDV isolates. The QIAP1401 isolate was determined to be closely related to the USA/Minnesota271/2014 strain (> 99.9% nucleotide similarity) that was isolated in the USA in 2014. Phylogenetic analysis based on several PEDV genes suggested that a new PEDV variant is circulating in the Korean swine industry, with 93.08% similarity to the SM98 strain isolated in 1998. In addition, the QIAP1401 strain showed strong virulence in 3-day-old piglets and 11-week-old growing pigs.


title: Infectious disease emergencies: role of the infectious disease specialist

text: ABSTRACT The importance of infections for public health has become obvious during the last decades. Examples are emerging infections such as HIV/AIDS and severe acute respiratory syndrome, deliberate release of microorganisms, such as the anthrax episode in the USA, the increasing problems with organisms resistant to antimicrobial treatment, such as methicillin-resistant Staphylococcus aureus, and the threat of a new influenza pandemic with a case fatality rate similar to that in the 1918 outbreak. An effective response to infectious disease emergencies requires careful planning and establishment of resources in advance. The medical specialties involved are clinical microbiology, clinical infectious diseases and epidemiology. Clinical microbiology should include bacteriology, virology and parasitology; the technical developments during the last 15 years have clearly erased most of the methodological differences between these branches of microbiology. New techniques such as new generations of Polymerase Chain Reaction (PCR), rapid methods for nucleic acid sequence analyses and microarrays have enabled more rapid identification of organisms and provide powerful tools in the epidemiological analysis of an outbreak. The infectious disease specialists are necessary for rapid and adequate clinical diagnoses, optimal use of antimicrobial agents and provision of facilities for containment of patients who may spread the infections. The need for isolation units became acute when many countries prepared themselves for a possible severe acute respiratory syndrome outbreak in Europe. With few exceptions, Europe still lacks epidemiological field forces, and it has been embarrassing to be obliged to call upon the Centers for Disease Control for European outbreaks. Hopefully, this will be corrected with the creation of the European Centre for Disease Prevention and Control (ECDC).


title: Identification of mutations in a temperature‐sensitive mutant (tsm5) of murine cytomegalovirus using complementary genome sequencing

text: Identification of mutations in mutants derived chemically is a difficult and relatively random process. NimbleGen Comparative Genome Sequencing (CGS) was assessed as an inexpensive, rapid method of identifying mutations in the temperature‐sensitive mutant tsm5 of the K181 (Birmingham) variant of murine cytomegalovirus (MCMV). This genome resequencing approach requires an established genome sequence as a reference. Comparison of tsm5 and the K181 (Birmingham) variant with the published K181 (Perth) MCMV genomic sequence revealed a total of 10 synonymous and 15 non‐synonymous SNPs in tsm5 and 14 of the latter were confirmed by sequencing. Thus, while CGS cannot be relied upon to identify correctly all mutations it was helpful for identifying a large number of mutations for further investigation that could contribute to the ts phenotype of tsm5. J. Med. Virol. 81:511–518, 2009. © 2009 Wiley‐Liss, Inc.


title: The SARS coronavirus nucleocapsid protein – Forms and functions

text: Abstract The nucleocapsid phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV N protein) packages the viral genome into a helical ribonucleocapsid (RNP) and plays a fundamental role during viral self-assembly. It is a protein with multifarious activities. In this article we will review our current understanding of the N protein structure and its interaction with nucleic acid. Highlights of the progresses include uncovering the modular organization, determining the structures of the structural domains, realizing the roles of protein disorder in protein–protein and protein–nucleic acid interactions, and visualizing the ribonucleoprotein (RNP) structure inside the virions. It was also demonstrated that N-protein binds to nucleic acid at multiple sites with a coupled-allostery manner. We propose a SARS-CoV RNP model that conforms to existing data and bears resemblance to the existing RNP structures of RNA viruses. The model highlights the critical role of modular organization and intrinsic disorder of the N protein in the formation and functions of the dynamic RNP capsid in RNA viruses. This paper forms part of a symposium in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.”


title: Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients

text: BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a serious of clinical symptoms and severe illness, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining were performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of Alveolar macrophage by SARS-CoV-2 might be drivers of the “cytokine storm”, which might result in damages in pulmonary tissues, heart and lung, and leading to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China


title: Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID‐19 patients: A meta‐regression and Decision tree analysis

text: BACKGROUND: Coronavirus disease‐2019 (COVID‐19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID‐19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID‐19 patients. RESULTS: A meta‐analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73‐7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84‐4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID‐19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.


title: Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells

text: Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-without of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment.


title: Janus faced course of COVID‐19 infection in patients with hematological malignancies

text: The COVID‐19 pandemic affects most countries of the world resulting in significant morbidity and mortality from this infection with SARS‐CoV2 (1). It was reported that among others specifically patients with cancer (including patients with hematological malignancies) are at a higher risk for severe and fatal infection (2). Here, we report three consecutive patients with underlying hematologic malignancies and co‐morbidities who were admitted to the infectious diseases ward at our department because of SARS‐CoV2 infection.


title: Exploring Public Health’s roles and limitations in advancing food security in British Columbia

text: OBJECTIVES: This research analyzes the roles and limitations of Public Health in British Columbia in advancing food security through the integration of food security initiatives into its policies and programs. It asks the question, can Public Health advance food security? If so, how, and what are its limitations? METHODS: This policy analysis merges findings from 38 key informant interviews conducted with government and civil society stakeholders involved in the development of food security initiatives, along with an examination of relevant documents. The Population Health Template is used to delineate and analyze Public Health roles in food security. RESULTS: Public Health was able to advance food security in some ways, such as the adoption of food security as a core public health program. Public Health’s leadership role in food security is constrained by a restricted mandate, limited ability to collaborate across a wide range of sectors and levels, as well as internal conflict within Public Health between Food Security and Food Protection programs. CONCLUSIONS: Public Health has a role in advancing food security, but it also faces limitations. As the limitations are primarily systemic and institutional, recommendations to overcome them are not simple but, rather, require movement toward embracing the determinants of health and regulatory pluralism. The results also suggest that the historic role of Public Health in food security remains salient today.


title: Bacterial Interference of Ubiquitination and Deubiquitination

text: Ubiquitination and deubiquitination regulate several essential cellular processes such as protein degradation, cell-cycle progression, signaling, and DNA repair. Given the importance of these processes, it is not surprising that many microbes have developed the means to interfere with different stages of ubiquitin pathways to promote their survival and replication. This review focuses on virulence proteins of bacterial pathogens that mediate these effects and summarizes our current understanding of their actions.


title: Development of a sensitive and specific xMAP assay for detection of antibodies against infectious laryngotracheitis and bronchitis viruses

text: BACKGROUND: A serological method to simultaneously detect antibodies against infectious laryngotracheitis virus (ILTV) and infectious bronchitis virus (IBV) is imperative for the differential diagnosis and evaluation of antibodies titers after vaccination. METHOD: The microspheres coated with purified recombinant glycoprotein D (gD) of ILTV or nucleocapsid (N) protein of IBV were incubated with serum samples. The simultaneous quantification of ILTV and IBV antibodies were achieved through the interrogation of microspheres by Luminex 200 detection system. . RESULTS: This xMAP detection demonstrated no nonspecific reactions with avian influenza virus (AIV), avian leukosis virus (ALV), newcastle disease virus (NDV), and Marek’s disease virus (MDV). The results also demonstrated that the xMAP assay was four times more sensitive than the enzyme-linked immunosorbent assay (ELISA) for ILTV detection and two times more sensitive for IBV detection. A total of 90 chicken serum samples from a chicken farm were tested by xMAP and ELISA assays. The results showed that the coincidence rates were 84.44 and 100% for ILTV and IBV detection, respectively. CONCLUSION: This study exhibited an opportunity for the differential diagnosis through simultaneous detection of multiplex antibodies in serum and can be used for the multiplex antibodies evaluation after vaccination.


title: Embryonic expression patterns of Eukaryotic EndoU ribonuclease family gene endouC in zebrafish

text: Abstract Endou proteins belong to the Eukaryotic EndoU ribonuclease family of enzymes that present high sequence homology with the founding member XendoU domain. The enzymatic activity and three-dimensional structure of some Endou proteins have been previously reported. However, their molecular structure and gene expression patterns during embryogenesis remain to be elucidated. Therefore, we took zebrafish (Danio rerio) endouC as the model to study molecular structure and gene expression dynamics at different developmental stages. Zebrafish endouC cDNA contains 930 base pairs encoding 309 amino acid residues, sharing 27%, 27%, 27%, and 25% identity with that of human, mouse, chicken and frog, respectively. A phylogenetic tree showed that zebrafish EndouA was clustered with vertebrate Endou groups, while zebrafish EndouB and EndouC were found to belong to a unique monophyletic group. Furthermore, the endouC transcript was detected in one-cell embryos, suggesting that it is a maternal gene. While the endouC transcript was only weakly present at early developmental stages, its expression was greatly increased in embryos from 18 to 48 h post-fertilization (hpf) and then decreased after 72 hpf. Finally, endouC was ubiquitously expressed throughout the whole embryo during early embryogenesis, but its expression was enriched in brain, eyes and fin buds from 24 to 96 hpf.


title: Copious production of SARS-CoV nucleocapsid protein employing codon optimized synthetic gene

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP) is one of the predominant antigenic protein and the most abundant shed antigen throughout the SARS-CoV infection. This feature makes it a suitable molecular target for diagnostic applications. In this study the full length codon optimized NP gene and its subfragment gene segment was cloned in a bacterial expression vector. The full length NP could be expressed in E. coli at very high level within inclusion bodies. The inclusion bodies were successfully solubilized, purified under denaturing conditions employing IMAC column and refolded. The non-glycosylated NP was used to immunize mice for hybridoma development. The polyclonal antiserum from animals immunized with this recombinant NP protein was found to specifically recognize the NP and its subfragments, thus demonstrating the immunogenic nature of the recombinant protein. The NP antigen or a subfragment could be useful for developing a sensitive serum diagnostic assay to monitor SARS-CoV outbreaks by detecting the early human anti-SARS antibodies. In addition, the availability of the NP fragments could facilitate epitope mapping of anti-NP monoclonals for identifying suitable sandwich pairs.


Summary of recommendations regarding COVID‐19 in children with diabetes: Keep Calm and Mind your Diabetes Care and Public Health Advice


title: Comparative pathogenesis of US porcine epidemic diarrhea virus (PEDV) strain PC21A in conventional 9-day-old nursing piglets vs. 26-day-old weaned pigs

text: Abstract Our study demonstrated potential mechanisms by which porcine epidemic diarrhea virus (PEDV) infection induces greater disease severity of nursing vs. weaned conventional pigs. Twenty-six-day-old weaned [PEDV-inoculated (n =11); mock (n =9)] and 9-day-old nursing pigs [PEDV-inoculated (n =9); mock (n =11)] were inoculated orally [8.9 log10 genomic equivalents (GE)/pig] with PC21A strain or mock (MEM). Pigs were monitored for clinical signs and PEDV RNA titers in feces and serum. For pathology and immunofluorescence staining for Ki67 (marker for crypt proliferation) and LGR5 (marker for crypt stem cell), 3–4 pigs were euthanized at postinoculation days (PIDs) 1, 3 and 5. Severe watery diarrhea and atrophic enteritis with moderate to high PEDV RNA titers in feces (7.5–12.2 log10 GE/ml) and low viral RNA titers in serum (5.6–8.6 log10 GE/ml) were observed in all inoculated nursing piglets at PIDs 1–5. In contrast, weaned pigs did not show evidence of PEDV infection at PID 1. Pigs exhibited high fecal shedding titers at PIDs 2–5 and mild to severe atrophic enteritis at PIDs 3–5, indicating a longer incubation for PEDV infection. While uninoculated or inoculated 27–31-day-old pigs showed large numbers of Ki67- or LGR5-positive cells in the intestinal crypts, there was a lack of LGR5-positive cells and low proliferation of crypts in jejunum of uninoculated 10–14-day-old piglets, possibly causing a slower turnover of enterocytes; however, the number of LGR5-positive cells and proliferation of intestinal crypts increased remarkably at 3–5 days after inoculation. Biologic mediators that promote crypt stem cell regeneration would be targets to improve the intestinal epithelium renewal during PEDV infection.


title: SARS‐CoV‐2 and the Hidden Carriers – Sewage, Feline, and Blood Transfusion

text: We have read with great interests a recent article showing SARS‐CoV‐2 viral RNA in feces of children during their recovery period from the disease.(1) The study showed that even though no viral nucleic acid was detected in the throat swab specimens, the virus was identified in their feces samples. More recently, Li et al(2) and Liu et al.(3) detected the virus nucleic acid in the feces and sputum of discharged patients of the disease following quarantine protocol in their homes. This article is protected by copyright. All rights reserved.


title: Subchapter 29D Angiotensin Converting Enzymes

text: Abstract Angiotensin converting enzyme (ACE) is well known for its dual actions in converting inactive Ang I to active Ang II and degrade active bradykinin (BK), which play an important role in the control of blood pressure. Since the bottle neck step is the production of pressor Ang II, this was targeted pharmacologically in 1970s and successful ACE inhibitors such as captopril were produced to treat hypertension. Researches on domain specific ACE inhibitors are continuing to produce effective hypertension controlling drugs with fewer side effects. ACE2 was discovered in 2000; it converts Ang II into Ang(1–7), thereby reducing the concentration of Ang II as well as increasing that of Ang(1–7), an important enzyme for Ang(1–7)/Mas receptor signaling. ACE2 also acts as the receptor in the lung for the coronavirus causing the infamous severe acute respiratory syndrome (SARS) in 2003.


title: Real-time analysis of quantum dot labeled single porcine epidemic diarrhea virus moving along the microtubules using single particle tracking

text: In order to study the infection mechanism of porcine epidemic diarrhea virus (PEDV), which causes porcine epidemic diarrhea, a highly contagious enteric disease, we combined quantum dot labeled method, which could hold intact infectivity of the labeled viruses to the largest extent, with the single particle tracking technique to dynamically and globally visualize the transport behaviors of PEDVs in live Vero cells. Our results were the first time to uncover the dynamic characteristics of PEDVs moving along the microtubules in the host cells. It is found that PEDVs kept restricted motion mode with a relatively stable speed in the cell membrane region; while performed a slow-fast-slow velocity pattern with different motion modes in the cell cytoplasm region and near the microtubule organizing center region. In addition, the return movements of small amount of PEDVs were also observed in the live cells. Collectively, our work is crucial for understanding the movement mechanisms of PEDV in the live cells, and the proposed work also provided important references for further analysis and study on the infection mechanism of PEDVs.


title: Microstructure of atmospheric particles revealed by TXM and a new mode of influenza virus transmission

text: Abstract For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.


We Asked the Experts: Virtual Learning in Surgical Education During the COVID-19 Pandemic—Shaping the Future of Surgical Education and Training


title: Prolonged Virus Shedding Even after Seroconversion in a Patient with COVID-19

text: • Prolonged virus shedding could be found among COVID-19 patients after clinical symptoms resolved and specific antibody emerged. • Viral detection from throat gargling sample could be an alternative diagnostic method for mild COVID-19 patients with scarce sputum. • Sputum remained the most sensitive specimen for viral detection after clinical symptoms resolved.


title: Mucosal and systemic immune responses elicited by recombinant Lactococcus lactis expressing a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis

text: Abstract We constructed a food-grade expression system harboring a F1S1 fusion protein of Bordetella pertussis to be produced in Lactococcus lactis NZ3900 as a new oral vaccine model against whooping cough, caused by B. pertussis. F1S1 was composed of N-terminally truncated S1 subunit of pertussis toxin and type I immunodominant domain of filamentous hemagglutinin which are both known as protective immunogens against pertussis. The recombinant L. lactis was administered via oral or intranasal routes to BALB/c mice and the related specific systemic and mucosal immune responses were then evaluated. The results indicated significantly higher levels of specific IgA in the lung extracts and IgG in sera of mucosally-immunized mice, compared to their controls. It was revealed that higher levels of IgG2a, compared to IgG1, were produced in all mucosally-immunized mice. Moreover, immunized mice developed Th1 responses with high levels of IFN-γ production by the spleen cells. These findings provide evidence for L. lactis to be used as a suitable vehicle for expression and delivery of F1S1 fusion protein to mucosa and induction of appropriate systemic and mucosal immune responses against pertussis.


title: Psychological well-being among older adults during the COVID-19 outbreak: a comparative study of the young–old and the old–old adults

text: The COVID-19 outbreak could be considered as an uncontrollable stressful life event. Lockdown measures have provoked a disruption of daily life with a great impact over older adults’ health and well-being. Nevertheless, eudaimonic well‐being plays a protective role in confronting adverse circumstances, such as the COVID-19 situation. This study aims to assess the association between age and psychological well-being (personal growth and purpose in life). Young–old (60–70 years) and old–old (71–80 years) community-dwelling Spaniards (N = 878) completed a survey and reported on their sociodemographic characteristics and their levels of health, COVID-19 stress-related, appraisal, and personal resources. Old–old did not evidence poorer psychological well-being than young–old. Age has only a negative impact on personal growth. The results also suggest that the nature of the COVID-19 impact (except for the loss of a loved one) may not be as relevant for the older adults’ well-being as their appraisals and personal resources for managing COVID-related problems. In addition, these results suggest that some sociodemographic and health-related variables have an impact on older adults’ well-being. Thus, perceived-health, family functioning, resilience, gratitude, and acceptance had significant associations with both personal growth and purpose in life. Efforts to address older adults’ psychological well-being focusing on older adults’ personal resources should be considered.


title: Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Healthcare Personnel

text: Healthcare settings can amplify transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), but knowledge gaps about the epidemiology of transmission remain. We conducted a retrospective cohort study among healthcare personnel in hospital units that treated MERS-CoV patients. Participants were interviewed about exposures to MERS-CoV patients, use of personal protective equipment, and signs and symptoms of illness after exposure. Infection status was determined by the presence of antibodies against MERS-CoV. To assess risk factors, we compared infected and uninfected participants. Healthcare personnel caring for MERS-CoV patients were at high risk for infection, but infection most often resulted in a relatively mild illness that might be unrecognized. In the healthcare personnel cohort reported here, infections occurred exclusively among those who had close contact with MERS-CoV patients.


title: SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China

text: BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children’s Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2–12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-α (11.54%) and IFN-γ (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant’s condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.


title: Psychological health, sleep quality, and coping styles to stress facing the COVID-19 in Wuhan, China

text: To understand Wuhan residents’ psychological reactions to the COVID-19 epidemic and offer a reference point for interventions, an online questionnaire survey was conducted. It included the Disorder 7-Item Scale (GAD-7), the Patient Health Questionnaire 9-Item Scale (PHQ-9), Athens Insomnia Scale, and Simplified Coping Style Questionnaire. Categorical data were reported as numbers and percentages. Multivariate logistic regression models were used to evaluate the association between demographic factors and anxiety, depression, sleep disorder, and passive coping style. A total of 1242 Wuhan residents investigated, 27.5% had anxiety, 29.3% had depression, 30.0% had a sleep disorder, and 29.8% had a passive response to COVID-19. Being female was the risk factor for anxiety (OR = 1.62) and sleep disorder (OR = 1.36); being married was associated with anxiety (OR = 1.75); having a monthly income between 1000 and 5000 CNY (OR = 1.44, OR = 1.83, OR = 2.61) or >5000 CNY (OR = 1.47, OR = 1.45, OR = 2.14) was a risk factor for anxiety, depression, and sleep disorder; not exercising (OR = 1.45, OR = 1.71, OR = 1. 85, OR = 1.71) was a common risk factor for anxiety, depression, sleep disorder, and passive coping style; and having a higher education level (bachelor’s degree and above) (OR = 1.40) was associated with having a sleep disorder. Wuhan residents’ psychological status and sleep quality were relatively poorer than they were before the COVID-19 epidemic; however, the rate of passive coping to stress was relatively higher.


title: Response to “Lupus anticoagulant is frequent in patients with Covid‐19”

text: We appreciate the opportunity to respond to the letter from Dr. Inès Harzallah, et al. Antiphospholipid antibody assays including lupus anticoagulant (LAC), anticardiolipin and anti–β2‐glycoprotein I have also been performed in dozens of our patients, however, very few of them got positive results, we don't think that antiphospholipid antibody exists universally in COVID‐19 patients. In addition, two of the three reported cases with antiphospholipid antibodies mentioned in the letter [1] also seem to meet the International Society on Haemostasis and Thrombosis (ISTH) criteria of disseminated intravascular coagulation [2], the causality between antiphospholipid antibodies and thrombosis in these cases is still uncertain.


title: Comparison of chest CT findings between COVID-19 pneumonia and other types of viral pneumonia: a two-center retrospective study

text: OBJECTIVES: To compare the pulmonary chest CT findings of patients with COVID-19 pneumonia with those with other types of viral pneumonia. METHODS: This retrospective review includes 154 patients with RT-PCR-confirmed COVID-19 pneumonia diagnosed between February 11 and 20, 2020, and 100 patients with other types of viral pneumonia diagnosed between April 2011 and December 2020 from two hospitals. High-resolution CT (HRCT) of the chest was performed. Data on location, distribution, attenuation, maximum lesion range, lobe involvement, number of lesions, air bronchogram signs, Hilar and mediastinal lymph node enlargement, and pleural effusion were collected. Associations between imaging characteristics and COVID-19 pneumonia were analyzed with univariate and multivariate logistic regression models. RESULTS: A peripheral distribution was associated with a 13.04-fold risk of COVID-19 pneumonia, compared with a diffuse distribution. A maximum lesion range > 10 cm was associated with a 9.75-fold risk of COVID-19 pneumonia, compared with a maximum lesion range ≤ 5 cm, and the involvement of 5 lobes was associated with an 8.45-fold risk of COVID-19 pneumonia, compared with a maximum lesion range ≤ 2. No pleural effusion was associated with a 3.58-fold risk of COVID-19 pneumonia compared with the presence of pleural effusion. Hilar and mediastinal lymph node enlargement was associated with a 2.79-fold risk of COVID-19 pneumonia. CONCLUSION: A peripheral distribution, a lesion range > 10 cm, involvement of 5 lobes, presence of hilar and mediastinal lymph node enlargement, and no pleural effusion were significantly associated with 2019-novel coronavirus pneumonia. KEY POINTS: • A peripheral distribution, a lesion range > 10 cm, involvement of 5 lobes, presence of hilar and mediastinal lymph node enlargement, and no pleural effusion were significantly associated with COVID-19 compared with other types of viral pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06925-3) contains supplementary material, which is available to authorized users.


title: International Conferences on Environmental Mutagens in Human Populations—Opportunities, Accomplishments and Challenges

text: Abstract A major mission for organizing the series of International Conferences on Environmental Mutagens in Human Populations is to bring science and scientists to the sites where the field of environmental health is in developmental stages and environmental health is a serious concern. The mission has been fulfilled in each of the previous conferences that were held in Egypt, Czech Republic, Thailand and Brazil. These conferences have led to significant enhancement of regional scientific expertise from the acquisition of scientific knowledge and from the generation of sustainable collaborative programs.


title: Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens

text: Several human monoclonal antibodies (hmAbs) including b12, 2G12 and 2F5 exhibit relatively potent and broad HIV-1 neutralizing activity. However, their elicitation in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. We have hypothesized that HIV-1 has evolved a strategy to reduce or eliminate the immunogenicity of the highly conserved epitopes of such antibodies by using “holes” (absence or very weak binding to these epitopes of germline antibodies that is not sufficient to initiate and/or maintain an efficient immune response) in the human germline B cell receptor (BCR) repertoire. To begin to test this hypothesis we have designed germline-like antibodies corresponding most closely to b12, 2G12 and 2F5 as well as to X5, m44 and m46 which are cross-reactive but with relatively weak neutralizing activity as natively occurring antibodies due to size and/or other effects. The germline-like X5, m44 and m46 bound with relatively high affinity to all tested Envs. In contrast, germline-like b12, 2G12 and 2F5 lacked measurable binding to Envs in an ELISA assay although the corresponding mature antibodies did. These results provide initial evidence that Env structures containing conserved vulnerable epitopes may not initiate humoral responses by binding to germline antibodies. Even if such responses are initiated by very weak binding undetectable in our assay it is likely that they will be outcompeted by responses to structures containing the epitopes of X5, m44, m46, and other antibodies that bind germline BCRs with much higher affinity/avidity. This hypothesis, if further supported by data, could contribute to our understanding of how HIV-1 evades immune responses and offer new concepts for design of effective vaccine immunogens.


title: The Emergence of Human Coronavirus EMC: How Scared Should We Be?

text: A novel betacoronavirus, human coronavirus (HCoV-EMC), has recently been detected in humans with severe respiratory disease. Further characterization of HCoV-EMC suggests that this virus is different from severe acute respiratory syndrome coronavirus (SARS-CoV) because it is able to replicate in multiple mammalian cell lines and it does not use angiotensin-converting enzyme 2 as a receptor to achieve infection. Additional research is urgently needed to better understand the pathogenicity and tissue tropism of this virus in humans. In their recent study published in mBio, Kindler et al. shed some light on these important topics (E. Kindler, H. R. Jónsdóttir, M. Muth, O. J. Hamming, R. Hartmann, R. Rodriguez, R. Geffers, R. A. Fouchier, C. Drosten, M. A. Müller, R. Dijkman, and V. Thiel, mBio 4[1]:e00611-12, 2013). These authors report the use of differentiated pseudostratified human primary airway epithelial cells, an in vitro model with high physiological relevance to the human airway epithelium, to characterize the cellular tropism of HCoV-EMC. More importantly, the authors demonstrate the potential use of type I and type III interferons (IFNs) to control viral infection.


title: Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome

text: BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1–7. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. METHODS: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. RESULTS: Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). CONCLUSION: These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.


title: Healthcare-associated infections in neonatal units: lessons from contrasting worlds

text: Summary Neonatal intensive care units are vulnerable to outbreaks and sporadic incidents of healthcare-associated infections (HAIs). The incidence and outcome of these infections are determined by the degree of immaturity of the neonatal immune system, invasive procedures involved, the aetiological agent and its antimicrobial susceptibility pattern and, above all, infection control policies practised by the unit. It is important to raise awareness of infection control practices in resource-limited settings, since overdependence upon antimicrobial agents and co-existing lack of awareness of infection control is encouraging the emergence of multi-drug-resistant nosocomial pathogens. We reviewed 125 articles regarding HAIs from both advanced and resource-limited neonatal units in order to study risk factors, aetiological agents, antimicrobial susceptibility patterns and reported successes in infection control interventions. The articles include surveillance studies, outbreaks and sporadic incidents. Gram-positive cocci, viruses and fungi predominate in reports from the advanced units, while Gram-negative enteric rods, non-fermenters and fungi are commonly reported from resource-limited settings. Antimicrobial susceptibility patterns from surveillance studies determined the empirical therapy used in each neonatal unit. Most outbreaks, irrespective of the technical facilities available, were traced to specific lack of infection control practices. We discuss infection control interventions, with special emphasis on their applicability in resource-limited settings. Cost-effective measures for implementing these interventions, with particular reference to the recognition of the role of the microbiologist, the infection control team and antibiotic policies are presented.


title: The legal extension of the role of pharmacists in light of the COVID-19 global pandemic

text: BACKGROUND: The COVID-19 epidemic has affected every area of life. The greatest challenge has been to adapt the functioning of the health service to prevent the spread of the epidemic and to help infected patients. This has required the involvement of not only doctors and nurses, but also pharmacists. In the face of this pandemic, governments in many countries have granted pharmacists greater authority. OBJECTIVES: The purpose of this paper is to review the legal extension of the role of pharmacists in light of the COVID-19 pandemic. The review considers recent changes in European countries, Canada, and the United States. METHODS: A literature review was performed to summarise knowledge about the extension of the role of pharmacists during the pandemic period. Key articles were retrieved mainly from PubMed and Google Scholar, using the terms “COVID‐19”, “2019‐nCoV”, “coronavirus”, and “pandemic” in combination with “pharmacist” as keywords for our search. We included scientific publications from February 1, 2019 to May 15, 2020. RESULTS: Pharmacists have been given numerous opportunities so that they can actively join in the fight against the virus. Some of the novel legal extensions aimed at aiding overloaded healthcare systems are as follows: authorisation to prepare hand and surface disinfectants, eligibility to renew chronic treatment prescriptions, as well as filling pro auctore and pro familia prescriptions by pharmacists, performing COVID-19, influenza, and Group A Streptococcus screening tests, and vaccine administration. Moreover, many countries have facilitated Internet services, such as virtual medical consultations, e-prescriptions, and home drug delivery – to promote social distancing among patients. To mitigate drug shortages, the following strategies have been implemented: alternative sourcing, strength, generic, or therapeutic substitution, and preparing compounded formulations at the pharmacy. CONCLUSIONS: Novel legal extensions have allowed exploitation of the full potential ofpharmacists worldwide, aiding the limited resources of overloaded healthcare systems.


title: Body Temperature Monitoring and SARS Fever Hotline, Taiwan

text: In Taiwan, a temperature-monitoring campaign and hotline for severe acute respiratory syndrome (SARS) fever were implemented in June 2003. Among 1,966 calls, fever was recorded in 19% (n = 378); 18 persons at high risk for SARS were identified. In a cross-sectional telephone survey, 95% (n = 1,060) of households knew about the campaign and 7 households reported fever.


Research Driven by Curiosity: The Journey from Basic Molecular Biology and Virology to Studies of Human Pathogenic Coronaviruses


title: Impact of COVID-19 on the Cardiovascular System: A Review

text: The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.


title: The airborne transmission of infection between flats in high-rise residential buildings: A review

text: The inter-flat airborne cross-transmission driven by single-sided natural ventilation has been identified recently in high-rise residential buildings, where most people live now in densely populated areas, and is one of the most complex and least understood transport routes. Given potential risks of infection during the outbreak of severe infectious diseases, the need for a full understanding of its mechanism and protective measures within the field of epidemiology and engineering becomes pressing. This review paper considers progress achieved in existing studies of the concerned issue regarding different research priorities. Considerable progress in observing and modeling the inter-flat transmission and dispersion under either buoyancy- or wind-dominated conditions has been made, while fully understanding the combined buoyancy and wind effects is not yet possible. Many methods, including on-site measurements, wind tunnel tests and numerical simulations, have contributed to the research development, despite some deficiencies of each method. Although the inter-flat transmission and dispersion characteristics can be demonstrated and quantified in a time-averaged sense to some extent, there are still unanswered questions at a fundamental level about transient dispersion process and thermal boundary conditions, calling for further studies with more advanced models for simulations and more sound experiments for validations.


title: Infection Control and SARS Transmission among Healthcare Workers, Taiwan

text: This study found infrequent transmission of severe acute respiratory syndrome (SARS) coronavirus to healthcare workers involved in the care of the first five case-patients in Taiwan, despite a substantial number of unprotected exposures. Nonetheless, given that SARS has been highly transmissible on some occasions, we still recommend strict precautions.


Facing the future—what lessons could we learn from Covid-19?


title: The prospects of modifying the antimicrobial properties of milk

text: Abstract Milk contains a variety of substances, which inhibit the infection of pathogens. This is of benefit to the mother, safeguarding the integrity of the lactating mammary gland, but also of huge importance for protection of the suckling offspring. The antimicrobial substances in milk can be classified into two categories. First, nonspecific, broad-spectrum defense substances, which have evolved over long periods of time, and secondly, substances like antibodies, which are specifically directed against particular pathogens and have developed during the mother's lifetime. Substances in both categories may be targets for biological intervention and manipulation with the goal of improving the antimicrobial properties of milk. These alterations of milk composition have applications in human as well as in animal health.


title: Evolution of tongue somatosensory evoked potentials in people with multiple sclerosis

text: INTRODUCTION: The aim of the present study was to investigate the long-term evolution of tongue somatosensory evoked potentials (tSSEP) in people with multiple sclerosis (pwMS). METHODS: Out of initial 121 participants, after two-year follow-up, the data were available for 74 and after four-year follow-up for 58 pwMS. In all pwMS complete neurological examination, brain MRI, cervical spinal cord MRI (if available) and tSSEP were performed at baseline visit (M0). Complete neurological examination and tSSEP were performed 2 and 4 years later (M24 and M48). tSSEP results were interpreted in the form of ordinal tSSEP score and quantitative tSSEP zscore calculated from the sum of z-transformed tSSEP latencies. RESULTS: Differences in tSSEP scores and tSSEP zscores in three different timepoints showed significant worsening of both scores over time. For the tSSEP score the difference was significant for M0-M24 and M0-M48 visits, but not for M24-M48 visits. For the tSSEP zscore the difference was significant for M0-M48 and M24-M48 visits, but not for M0-M24 visits. The only significant negative predictor found for the tSSEP score improvement was presence of cervical spinal cord lesions on the MRI. A moderate to high correlation was observed between both forms of tSSEP score at all three timepoints. CONCLUSION: This study demonstrates a significant deterioration of trigeminal sensory pathway in MS over time, giving further insight into trigeminal system damage in pwMS.


title: Selection of reference genes for quantitative real-time PCR analysis in chicken embryo fibroblasts infected with avian leukosis virus subgroup J

text: BACKGROUND: The selection of stably expressed reference genes is a prerequisite when evaluating gene expression, via real-time PCR, in cells in response to viral infections. The objective of our study was to identify suitable reference genes for mRNA expression analysis in chicken embryonic fibroblasts (CEF) after infection with avian leukosis virus subgroup J (ALV-J). FINDINGS: The expression levels of 11 potential reference genes in CEF infected with ALV-J were determined by real-time PCR. The expression stability of these genes were analyzed and ranked using the geNorm tool. Analysis indicated that the genes RPL30 (ribosomal protein L30) and SDHA (succinate dehydrogenase complex, subunit A) were the most stably expressed genes in the ALV-J infected CEF. CONCLUSIONS: The RPL30 and SDHA were deemed suitable for use as reference genes for real-time PCR analysis of mRNA gene expression during ALV-J infection, whereas commonly used ACTB and GAPDH are unsuitable to be reference genes.


title: The Role of Carbohydrates in Infection Strategies of Enteric Pathogens

text: Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.


title: A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways

text: Abstract A human microsatellite DNA-mimicking ODN (MS ODN) composed of CCT repeats, designated as SAT05f, has been studied for its capacity of negatively regulating innate immunity induced by TLR7/TLR9 agonists in vitro and in mice. The result showed that SAT05f could down-regulate TLR7/9-dependent IFN-α production in cultured human PBMC stimulated by inactivated Flu virus PR8 or HSV-1 or CpG ODN or imiquimod, protect d-GalN-treated mice from lethal shock induced by TLR9 agonist, not by TLR3/4 agonist. In addition, SAT05f significantly inhibit IFN-α production from purified human plasmacytoid cells (pDCs) stimulated by CpG ODN. Interestingly, SAT05f could up-regulate CD80, CD86, and HLA-DR on the pDCs in vitro, implying that SAT05f-mediated inhibition on IFN-α production could be related to the activation of pDCs. The data suggest that SAT05f could be developed as a candidate medicament for the treatment of TLR7/9 activation-associated diseases by inhibiting TLR7/9 signaling pathways.


Nonproliferative and Proliferative Lesions of the Ratand Mouse Special Sense Organs(Ocular [eye and glands], Olfactory and Otic)


COVID-19 Patients: Are Current Isolation Guidelines Effective Enough?


title: Japanese Encephalitis Viruses from Bats in Yunnan, China

text: Genome sequencing and virulence studies of 2 Japanese encephalitis viruses (JEVs) from bats in Yunnan, China, showed a close relationship with JEVs isolated from mosquitoes and humans in the same region over 2 decades. These results indicate that bats may play a role in human Japanese encephalitis outbreaks in this region.


title: Complete Genome Sequence of Avian Coronavirus Strain D274

text: Avian coronavirus, the causative agent of avian infectious bronchitis, occurs as multiple genotypes and lineages, and full genomes are not available for the majority of them. This paper reports the (previously unknown) complete genome sequence of strain D274 of this virus (27,599 nucleotides), isolated from chickens in The Netherlands in 1979.