title: Size-Segregated Particle Number Concentrations and Respiratory Emergency Room Visits in Beijing, China

text: BACKGROUND: The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies. OBJECTIVES: The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China. METHODS: Data on particle size distributions from 3 nm to 1 μm; PM(10) (PM ≤ 10 μm), nitrogen dioxide (NO(2)), and sulfur dioxide concentrations; and meteorologic variables were collected daily from March 2004 to December 2006. Concurrently, daily counts of emergency room visits (ERV) for respiratory diseases were obtained from the Peking University Third Hospital. We estimated pollutant effects in single- and two-pollutant generalized additive models, controlling for meteorologic and other time-varying covariates. Time-delayed associations were estimated using polynomial distributed lag, cumulative effects, and single lag models. RESULTS: Associations of respiratory ERV with NO(2) concentrations and 100–1,000 nm particle number or surface area concentrations were of similar magnitude—that is, approximately 5% increase in respiratory ERV with an interquartile range increase in air pollution concentration. In general, particles < 50 nm were not positively associated with ERV, whereas particles 50–100 nm were adversely associated with respiratory ERV, both being fractions of ultrafine particles. Effect estimates from two-pollutant models were most consistent for NO(2). CONCLUSIONS: Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO(2) concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM(10) or particle number concentrations in Beijing.


title: Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

text: Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses.


title: Mental Health of Young Physicians in China During the Novel Coronavirus Disease 2019 Outbreak

text: This cohort study assesses anxiety, depression, mood, and fear of workplace violence in a cohort of young physicians in China before and during the coronavirus disease 2019 outbreak.


title: Pragmatic multicentre randomised controlled trial evaluating the impact of a routine molecular point-of-care ‘test-and-treat’ strategy for influenza in adults hospitalised with acute respiratory illness (FluPOC): trial protocol

text: BACKGROUND: Influenza infections often remain undiagnosed in patients admitted to hospital due to lack of routine testing. When tested for, the diagnosis and treatment of influenza are often delayed due to the slow turnaround times of centralised laboratory PCR testing. Newer molecular systems, have comparable accuracy to laboratory PCR testing, and can generate a result in under 1 hour, making them potentially deployable as point-of-care tests (POCTs). High-quality evidence for the impact of routine POCT for influenza on clinical outcomes is, however, currently lacking. This large pragmatic multicentre randomised controlled trial aims to address this evidence gap. METHODS AND ANALYSIS: The FluPOC trial is a pragmatic, multicentre, randomised controlled trial evaluating adults admitted to a large teaching hospital and a district general hospital with an acute respiratory illness, during influenza season and defined by Public Health England. Up to 840 patients will be recruited over up to three influenza seasons, and randomised (1:1) to receive either POCT using the FilmArray respiratory panel, or routine clinical care. Clinical and infection control teams will be informed of the results in real time and where influenza is detected clinical teams will be encouraged to offer neuraminidase inhibitor (NAI) treatment in accordance with national guidelines. Those allocated to standard clinical care will have a swab taken for later analysis to allow assessment of missed diagnoses. The outcomes assessment will be by retrospective case note analysis. The outcome measures include the proportion of influenza-positive patients detected and appropriately treated with NAIs, isolation facility use, antibiotic use, length of hospital stay, complications and mortality. ETHICS AND DISSEMINATION: Prior to commencing the study, approval was obtained from the South Central Hampshire A Ethics Committee (reference 17/SC/0368, granted 7 September 2017). Results generated from this protocol will be published in peer-reviewed scientific journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN17197293


title: Prospects for the use of spherical gold nanoparticles in immunization

text: Recent years have seen extremely fast development of new viral nanovaccines and diagnostic agents using nanostructures prepared by biological and chemical synthesis. We used spherical gold nanoparticles (average diameter, 15 nm) as a platform for the antigen for swine transmissible gastroenteritis virus (TGEV). The literature data demonstrate that immunization of animals with the TGEV antigen coupled to gold nanoparticles (GNPs) not only activates antigen-presenting cells but also increases the proliferative activity of splenic lymphoid (antibody-forming) cells. The contents of γ-IFN, IL-1β, and IL-6 in animals immunized with GNP-antigen conjugates were found to be higher than those in intact animals or in animals given the antigen alone. The increased concentration of IL-1β in the immunized animals directly correlated with the activity of macrophages and stimulated B cells, which produce this cytokine when activated. The increased concentration of IL-6 indicates that the injected preparations are stimulatory to cellular immunity. Immunization with the TGEV antigen conjugated to GNPs as a carrier activates the respiratory activity of lymphoid cells and peritoneal macrophages, which is directly related to their transforming activity and to the activation of antibody generation. Furthermore, the use of this conjugate allows marked improvement of the structure of the animals’ immune organs and restores the morphological–functional state of these organs. The microanatomical changes (increased number of follicles) indicate the activation of the B-dependent zone of the spleen and, consequently, the development of a humoral-type immunological reaction. The degradative processes observed in the animals immunized with TGEV antigen alone are evidence of weak resistance to pathogen attack. These results can be used to develop vaccines against this infection by employing TGEV antigen coupled to gold nanoparticles as a carrier.


title: Viruses and autoimmune disease – two sides of the same coin?

text: Abstract Some viruses have the ability to modulate the development of autoimmune diseases. Virus infections have long been associated with the exacerbation of autoimmune disease, however, there is also evidence that viruses can actually protect against autoimmune disease. Several experimental models have been developed to investigate how some virus infections can prime for and trigger autoimmunity whereas others ameliorate the pathway leading to clinical disease. It is possible that the type I interferons, via interleukin 12, provide the link between viruses and autoimmunity.


title: Production of valuable compounds by molds and yeasts

text: We are pleased to dedicate this paper to Dr Julian E Davies. Julian is a giant among microbial biochemists. He began his professional career as an organic chemistry PhD student at Nottingham University, moved on to a postdoctoral fellowship at Columbia University, then became a lecturer at the University of Manchester, followed by a fellowship in microbial biochemistry at Harvard Medical School. In 1965, he studied genetics at the Pasteur Institute, and 2 years later joined the University of Wisconsin in the Department of Biochemistry. He later became part of Biogen as Research Director and then President. After Biogen, Julian became Chair of the Department of Microbiology at the University of British Columbia in Vancouver, Canada, where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian’s areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian’s accomplishments to continue into the future.


title: Microbiological safety of drinking water: United States and global perspectives.

text: Waterborne disease statistics only begin to estimate the global burden of infectious diseases from contaminated drinking water. Diarrheal disease is dramatically underreported and etiologies seldom diagnosed. This review examines available data on waterborne disease incidence both in the United States and globally together with its limitations. The waterborne route of transmission is examined for bacterial, protozoal, and viral pathogens that either are frequently associated with drinking water (e.g., Shigella spp.), or for which there is strong evidence implicating the waterborne route of transmission (e.g., Leptospira spp.). In addition, crucial areas of research are discussed, including risks from selection of treatment-resistant pathogens, importance of environmental reservoirs, and new methodologies for pathogen-specific monitoring. To accurately assess risks from waterborne disease, it is necessary to understand pathogen distribution and survival strategies within water distribution systems and to apply methodologies that can detect not only the presence, but also the viability and infectivity of the pathogen.


title: Triple Immunoglobulin Gene Knockout Transchromosomic Cattle: Bovine Lambda Cluster Deletion and Its Effect on Fully Human Polyclonal Antibody Production

text: Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs) in transchromosomic (Tc) cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambda-chain (hIGL) germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM(−/−), bIGHML1(−/−); double knockouts or DKO). However, because endogenous bovine immunoglobulin light chain loci are still intact, the light chains are produced both from the hIGK and hIGL genomic loci on the HAC and from the endogenous bovine kappa-chain (bIGK) and lambda-chain (bIGL) genomic loci, resulting in the production of fully hIgGs (both Ig heavy-chains and light-chains are of human origin: hIgG/hIgκ or hIgG/hIgλ) and chimeric hIgGs (Ig heavy-chains are of human origin while the Ig light-chains are of bovine origin: hIgG/bIgκ or hIgG/bIgλ). To improve fully hIgG production in Tc cattle, we here report the deletion of the entire bIGL joining (J) and constant (C) gene cluster (bIGLJ1-IGLC1 to bIGLJ5-IGLC5) by employing Cre/loxP mediated site-specific chromosome recombination and the production of triple knockout (bIGHM(−/−), bIGHML1(−/−) and bIGL(−/−); TKO) Tc cattle. We further demonstrate that bIGL cluster deletion greatly improves fully hIgGs production in the sera of TKO Tc cattle, with 51.3% fully hIgGs (hIgG/hIgκ plus hIgG/hIgλ).


COVID-19: Framework for the Resumption of Endoscopic Activities From the Canadian Association of Gastroenterology


title: An exploration of midwives’ role in the promotion and provision of antenatal influenza immunization: A Mixed Methods Inquiry.

text: Abstract Problem No South Australian study has previously investigated the role of midwives in the promotion and provision of antenatal influenza immunization. Background Influenza acquired in pregnancy can have serious sequalae for both mother and fetus. Recent studies have demonstrated that influenza vaccine in pregnancy is both safe and effective. Despite this, evidence suggests that vaccine uptake in pregnancy is suboptimal in both Australia and worldwide. Aim The aim of this study was to investigate the role of midwives in the promotion and provision of antenatal influenza vaccine and, to provide a statistical and thematic description of the barriers and enablers midwives encounter. Methods This mixed method study incorporated a cross sectional on-line survey and in-depth interviews conducted with midwives, employed in urban and regional South Australia. Findings Quantitative data were available for 137 midwives and 10 midwives participated in the interviews. Recruitment for the interview phase was through the last question on the survey. Whilst all midwives indicated that education and vaccine promotion were part of their role, immunization knowledge varied between Registered Nurse/Midwives (RM/RN) 80% and Registered Midwives (RM) 48.90% (p=0.001). Quantitative data showed that only 43% of midwives felt sufficiently educated to provide the vaccine. Midwives who had received formal immunization training were more likely to recommend the vaccine 93.7% (p =0.001). Qualitative data confirmed these results and identified the lack of immunization education as a barrier to practise. Conclusion Midwives identified an immunization knowledge deficit. Midwives who had received immunization education were more likely to actively promote and provide the vaccine to pregnant women. These findings indicate the need for more immunization education of midwives in both tertiary and practice settings.


title: Letter: intestinal inflammation, COVID‐19 and gastrointestinal ACE2—exploring RAS inhibitors. Authors’ reply

text: LINKED CONTENT This article is linked to Taxonera et al an Garg et al papers. To view these articles, visit https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.15814.


title: Viruses are a dominant driver of protein adaptation in mammals

text: Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of proteins is unknown. Here, we analyze adaptation in ~1,300 virus-interacting proteins manually curated from a set of 9,900 proteins conserved across mammals. We show that viruses (i) use the more evolutionarily constrained proteins from the cellular functions they hijack and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. Our results demonstrate that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.


title: Schweres akutes respiratorisches Syndrom (SARS)

text: The sudden appearance of the severe acute respiratory syndrome (SARS) in 2003 demonstrated to the world at large that despite the high standard of medical care in affected countries, a highly contagious emerging infectious disease could spread rapidly worldwide. By application and improvement of stringent infection control measures, a further spread of SARS could be stopped and the disease could so far be defeated. In the meantime, decisive progress in the knowledge about the structure and further characteristics of the SARS coronavirus (SARS-CoV) have been made, including the likely virus reservoir and the ways of spread. Validated diagnostic tests are now available and are further being improved. Effective vaccines and antiviral agents are being developed. Of imminent importance to prepare against a resurgence of SARS, remain, besides an exact knowledge about the viral pathogen and its possible further behavior, constant vigilance, early recognition, and instant isolation of suspected cases of SARS.


title: Airborne biological hazards and urban transport infrastructure: current challenges and future directions

text: Exposure to airborne biological hazards in an ever expanding urban transport infrastructure and highly diverse mobile population is of growing concern, in terms of both public health and biosecurity. The existing policies and practices on design, construction and operation of these infrastructures may have severe implications for airborne disease transmission, particularly, in the event of a pandemic or intentional release of biological of agents. This paper reviews existing knowledge on airborne disease transmission in different modes of transport, highlights the factors enhancing the vulnerability of transport infrastructures to airborne disease transmission, discusses the potential protection measures and identifies the research gaps in order to build a bioresilient transport infrastructure. The unification of security and public health research, inclusion of public health security concepts at the design and planning phase, and a holistic system approach involving all the stakeholders over the life cycle of transport infrastructure hold the key to mitigate the challenges posed by biological hazards in the twenty-first century transport infrastructure.


title: Meeting report: 30th International Conference on Antiviral Research, in Atlanta, GA, USA

text: The 30th International Conference on Antiviral Research was held in Atlanta, GA, USA, from 21 to 25 May 2017. Each year, the International Society for Antiviral Research (ISAR) presents three major awards, this year to Mike Sofia (Elion award), David Chu (Holý award) and Maaike Everts (Prusoff award). Also this year, the inaugural ISAR Women in Science award lecture was presented by Priscilla Yang. For several years, International Conference on Antiviral Research (ICAR) has included at least one Keynote lecture, this year there were four. Although there are accounts of only these eight lectures, they reflect the diversity that is characteristic of ICAR – employment (academia, industry, public health), type of research (virus biology, potential antiviral targets, antiviral drugs, research organisation) and a range of viruses. For example, the viruses included were hepatitis C virus and hepatitis B virus (Mike Sofia), HIV and hepatitis B virus (David Chu), multiple antiviral projects (Maaike Everts), dengue (Priscilla Yang), rhinovirus C (Ann Palmenberg), polio (Mark Pallansch), HIV (Eric Hunter) and Zika virus (Pei-Yong Shi). This report ends with my personal comments giving examples in which this diversity can bring benefits. The 31st ICAR will be in Porto, Portugal, 11–15 June 2018.


title: Infrastructure and Contamination of the Physical Environment in Three Bangladeshi Hospitals: Putting Infection Control into Context

text: OBJECTIVE: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. METHODS: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. CONCLUSIONS: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness.


title: Bloodstream Infection by Saccharomyces cerevisiae in Two COVID-19 Patients after Receiving Supplementation of Saccharomyces in the ICU

text: Co-infections have an unknown impact on the morbidity and mortality of the new clinical syndrome called coronavirus disease 2019 (COVID-19) The syndrome is caused by the new pandemic coronavirus SARS-CoV-2 and it is probably connected with severe traces in the elements of the immune system Apart from possible Aspergillus infections, particularly in patients with acute respiratory distress syndrome (ARDS), other fungal infections could occur, probably more easily, due to the immunological dysregulation and the critical condition of these patients Probiotic preparations of Saccharomyces are broadly used for the prevention of antibiotic-associated complications, especially in the intensive care units (ICU) On the other hand, Saccharomyces organisms are reported as agents of invasive infection in immunocompromised or critically ill patients We report two cases of bloodstream infection by Saccharomyces in two patients hospitalised in the ICU, due to severe COVID-19, after Saccharomyces supplementation


title: Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens

text: Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271–330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans.


title: Estudio prospectivo para estimar la carga de hospitalización y visitas a urgencias de la gripe en población pediátrica en Bilbao (2010-2011)

text: Resumen Introducción El estudio se llevó a cabo para estimar la carga de enfermedad de la gripe confirmada por laboratorio en niños menores de 15 años. Pacientes y métodos Los niños que acudieron al Hospital Universitario de Basurto con síntomas de infección respiratoria aguda y/o fiebre aislada entre noviembre de 2010 y mayo de 2011 fueron incluidos en el estudio (NCT01592799). Se tomaron 2muestras de secreción nasofaríngea: una para un test de diagnóstico rápido en el Servicio de Urgencias y otra para análisis en laboratorio con reacción en cadena de la polimerasa en tiempo real y cultivo viral. Resultados Se seleccionó a un total de 501 niños, de los que 91 fueron hospitalizados. El diagnóstico de gripe se confirmó en 131 (26,1%); 120/410 (29,3%) fueron tratados ambulatoriamente y 11/91 (12,1%), hospitalizados. En 370/501 niños (73,9%) el resultado no fue positivo. La proporción de otros virus respiratorios fue 145/501 (28,9%) casos y de coinfección con otro virus respiratorio además de gripe de 7/501 (1,4%). Los tipos de virus de gripe fueron: A (H1N1 y H3N2) 53,2% (67/126); B (Victoria y Yamagata) 46,0% (58/126); A+B 0,8% (1/126). El coste médico directo medio asociado con cada caso de gripe confirmada fue de 177,00€ (N=131). No se observaron diferencias estadísticamente significativas entre el coste asociado con gripe A o B. Conclusión Casi la mitad de los casos fueron virus de gripe B. La administración de una vacuna que incluya tipos A y B de gripe debería reducir la carga de la enfermedad. Abstract Introduction This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Patients and methods Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. Results A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A+B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N=131). No significant differences were observed between the medical costs associated with influenza A and B. Conclusion Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness.


title: Emodin Inhibits EBV Reactivation and Represses NPC Tumorigenesis

text: Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV- positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence.


title: Preventive strategy for the clinical treatment of hip fractures in the elderly during the COVID-19 outbreak: Wuhan’s experience

text: Hip fractures in the elderly account for more than half of osteoporotic fractures and represent a substantial economic and social burden. Novel coronavirus pneumonia (COVID-19), which began to spread in December 2019, has created challenges in the management of elderly hip fracture patients, not only by influencing the choice of operation and postoperative rehabilitation methods, but also by generating new risks for the medical staff. During this period, our infection and orthopedic treatment unit in the center of the epidemic area effectively treated 82 elderly patients with hip fracture, and no cross-infection occurred. Therefore, our experience in prevention and treatment is worth recommending to frontline anti-epidemic personnel.


title: Intra‐articular injections in people with haemophilia in the COVID‐19 era

text: Given the current SARS‐CoV‐2 pandemic, many patients with haemophilia will have close contact with a confirmed case or suffer from coronavirus 2019 respiratory disease (COVID‐19) and will need medical attention. Considering that this situation is exceptional, it is necessary to carry out integrated assistance for patients with haemophilia patients and their relatives, focusing such assistance on all the dimensions of life. In this regard, the WFH's recommendations to optimise haematological prophylaxis and its adherence should be emphasised to minimise the risk of bleeding and thus reduce the need to visit health care facilities [1].


title: Speeding tumor genotyping during the SARS‐CoV‐2 outbreak through liquid biopsy

text: This commentary proposes a shift in the current diagnostic workflow for patients with metastatic cancer to incorporate the use of liquid biopsy. This proposal, born in the time of a severe crisis for the health care system, might also be applied when the severe acute respiratory syndrome coronavirus 2 outbreak ends and thereby reduce the turnaround time for results from molecular testing for patients with cancer and increase the number of patients potentially benefiting from highly effective targeted therapies.


title: HIV envelope: challenges and opportunities for development of entry inhibitors

text: The HIV envelope proteins gp120 and gp41 play critical roles in HIV entry and thus are of extreme interest for the development of novel therapeutics. Study by diverse methods, including structural biology and mutagenesis, has resulted in a detailed model for envelope-mediated entry, which consists of multiple conformations, each a potential target for therapeutic intervention. In this review we discuss the challenges, strategies and progress to date for developing novel entry inhibitors directed at disrupting HIV gp120 and gp41 function.


docid: rsvrkvuk

title: Incorporating message format into user evaluation of microblog information credibility: A nonlinear perspective

text: The spreading of misinformation and disinformation is a great problem on microblogs, leading user evaluation of information credibility a critical issue. This study incorporates two message format factors related to multimedia usage on microblogs (vividness and multimedia diagnosticity) with two well-discussed factors for information credibility (i.e., argument quality and source credibility) as a holistic framework to investigate user evaluation of microblog information credibility. Further, the study draws on two-factor theory and its variant three-factor lens to explain the nonlinear effects of the above factors on microblog information credibility. An online survey was conducted to test the proposed framework by collecting data from microblog users. The research findings reveal that for the effects on microblog information credibility: (1) argument quality (a hygiene factor) exerts a decreasing incremental effect; (2) source credibility (a bivalent factor) exerts only a linear effect; and (3) multimedia diagnosticity (a motivating factor) exerts an increasing incremental effect. This study adds to current knowledge about information credibility by proposing an insightful framework to understand the key predictors of microblog information credibility and further examining the nonlinear effects of these predictors.


title: Pathogen–endoplasmic-reticulum interactions: in through the out door

text: A key determinant for the survival of intracellular pathogens is their ability to subvert the cellular processes of the host to establish a compartment that allows replication. Although most microorganisms internalized by host cells are efficiently cleared following fusion with lysosomes, many pathogens have evolved mechanisms to escape this degradation. In this Review, we provide insight into the molecular processes that are targeted by pathogens that interact with the endoplasmic reticulum and thereby subvert the immune response, ensure their survival intracellularly and cause disease. We also discuss how the endoplasmic reticulum 'strikes back' and controls microbial growth.


title: Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil

text: BACKGROUND: Bats have been implicated as the main reservoir of coronavirus (CoV). Thus the role of these hosts on the evolution and spread of CoVs currently deserve the attention of emerging diseases surveillance programs. On the view of the interest on and importance of CoVs in bats the occurrence and molecular characterization of CoV were conducted in bats from Brazil. FINDINGS: Three hundred five enteric contents of 29 bat species were tested using a panCoV nested RT-PCR. Nine specimens were positive and eight was suitable for RdRp gene sequencing. RdRp gene phylogeny showed that all CoVs strains from this study cluster in Alphacoronavirus genus, with one Molossidae and one Phlyllostomidae-CoV specific groups. Phylogenetic analyses of two S gene sequences showed a large diversity within the Alphacoronavirus genus. CONCLUSIONS: This study indicated a CoV-to-host specificity and draws attention for CoV detection in Cynomops sp, a potential new reservoir. The phylogenetic analyses indicate that diversity of CoV in bats is higher than previously known.


docid: zejwyzqk

title: Airborne precautions recommended in Wuhan, China for bedside fiberoptic bronchoscopy examination of patients with COVID-19.


title: Ferret care and husbandry

text: Convivial and playful, the ferret has cohabited with humans for hundreds of years. Maintenance of this mustelid's health and quality of life is paramount for the endurance of the human-animal bond. This review article for veterinary care givers, veterinarians, and staff, encompasses discussions on: husbandry, clinical techniques, prevalent diseases, history taking, physical examination, vaccination, and pain recognition. This article also enables the veterinary community to contribute to the care and welfare of ferret patients by offering facts to distinguish these animals from dogs and cats.


title: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event

text: Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.


docid: hdkmwihu

title: SARS-coronavirus (SARS-CoV) and the safety of a solvent/detergent (S/D) treated immunoglobulin preparation

text: Abstract SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. SARS-CoV viraemia does not seem to reach high titres, however, it has to be excluded that virus transmission may occur via blood transfusion or application of therapeutic plasma products, e.g. fresh-frozen plasma or single components derived thereof. Manufacturing processes of all plasma derivatives are required to comprise dedicated virus inactivation/removal steps. Treatment with a mixture of solvent and detergent (SD) has successfully been applied to inactivate the most members of the transfusion-relevant viruses without affecting therapeutic properties of the products. The SD treatment irreversibly disrupts the lipid envelope of viruses such as HIV, HBV, HCV, HGV and CMV. In this study we evaluated the manufacturing process of an immunoglobulin preparation (OCTAGAM, manufactured by Octapharma Pharmazeutika Produktionsges.m.b.H., Vienna, Austria) for its capacity to inactivate the SARS-CoV. Our results demonstrate that SARS-CoV was completely inactivated below the limit of detection. This was found to occur within 1min of SD treatment.


title: Will an obesity pandemic replace the coronavirus disease-2019 (COVID-19) pandemic?

text: [Figure: see text]


Histology of colitis:Saguinus oedipus oedipus and other marmosets


title: SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a highly basic nucleocapsid (N) protein which can inhibit the synthesis of type I interferon (IFN), but the molecular mechanism of this antagonism remains to be identified. In this study, we demonstrated that the N protein of SARS-CoV could inhibit IFN-beta (IFN-β) induced by poly(I:C) or Sendai virus. However, we found that N protein could not inhibit IFN-β production induced by overexpression of downstream signaling molecules of two important IFN-β induction pathways, toll-like receptor 3 (TLR3)- and RIG-I-like receptors (RLR)-dependent pathways. These results indicate that SARS-CoV N protein targets the initial step, probably the cellular PRRs (pattern recognition receptors)-RNAs-recognition step in the innate immune pathways, to suppress IFN expression responses. In addition, co-immunoprecipitation assays revealed that N protein did not interact with RIG-I or MDA5. Further, an assay using truncated mutants revealed that the C-terminal domain of N protein was critical for its antagonism of IFN induction, and the N deletion mutant impaired for RNA-binding almost completely lost the IFN-β antagonist activity. These results contribute to our further understanding of the pathogenesis of SARS-CoV.


title: Porcine DC-SIGN: Molecular cloning, gene structure, tissue distribution and binding characteristics()

text: DC-SIGN, a human C-type lectin, is involved in the transmission of many enveloped viruses. Here we report the cloning and characterization of the cDNA and gene encoding porcine DC-SIGN (pDC-SIGN). The full-length pDC-SIGN cDNA encodes a type II transmembrane protein of 240 amino acids. Phylogenetic analysis revealed that pDC-SIGN, together with bovine, canis and equine DC-SIGN, are more closely related to mouse SIGNR7 and SIGNR8 than to human DC-SIGN. pDC-SIGN has the same gene structure as bovine, canis DC-SIGN and mouse SIGNR8 with eight exons. pDC-SIGN mRNA expression was detected in pig spleen, thymus, lymph node, lung, bone marrow and muscles. pDC-SIGN protein was found to express on the surface of monocyte-derived macrophages and dendritic cells, alveolar macrophages, lymph node sinusoidal macrophage-like, dendritic-like and endothelial cells but not of monocytes, peripheral blood lymphocytes or lymph node lymphocytes. A BHK cell line stably expressing pDC-SIGN binds to human ICAM-3 and ICAM-2 immunoadhesins in a calcium-dependent manner, and enhances the transmission of porcine reproductive and respiratory syndrome virus (PRRSV) to target cells in trans. The results will help better understand the biological role(s) of DC-SIGN family in innate immunity during the evolutionary process.


title: Pneumonia aguda fibrinosa e organizante

text: Abstract The histologic pattern of Acute Fibrinous and Organizing Pneumonia (AFOP), described by Beasley in 2002, is characterized by the existence of intraalveolar fibrin in the form of fibrin “balls” and diffuse organizing pneumonia. Presenting symptoms of this interstitial pulmonary disease can be acute or subacute. However, it differs from the well-recognized histologic patterns of acute pulmonary lesion – Diffuse Alveolar Damage (DAD), Organizing Pneumonia (OP) and Eosinophilic Pneumonia (EP). The authors carry out a review of the literature concerning this topic and describe the clinical case of a 44-year-old patient with unusual imaging features and outcome. Rev Port Pneumol 2010; XVI (4): 607-616


title: LC16m8: An attenuated smallpox vaccine

text: The frequency of moderate to severe adverse reactions associated with smallpox vaccines currently stockpiled in the US, and the continued threat of bioterrorism have prompted the development of effective vaccines with improved safety profiles. LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. It has been shown to have markedly less neurotoxicity than unattenuated vaccines in nonclinical studies. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. This article reviews the history and available scientific literature regarding LC16m8 and provides comparisons to other smallpox vaccines.


title: New inflow boundary conditions for modeling twisted wind profiles in CFD simulation for evaluating the pedestrian-level wind field near an isolated building

text: Abstract The hilly topography of Hong Kong influences oncoming winds and gradually changes their wind directions along the profiles' height. The vertical variation in wind directions, or the twist effect, significantly influences the Pedestrian Level Wind (PLW) field in urban areas of Hong Kong, thus it is a topic demanding systematic investigations. In this study, a new set of inflow boundary conditions are proposed to model twisted wind flows in Computational Fluid Dynamic (CFD) simulations. The new inflow boundary condition derived based on the horizontal homogeneous assumption, specifies a vertical profile of lateral wind speeds at the inlet boundary to sustain the twist effect in the empty computational domain. The proposed boundary conditions are used to simulate the PLW fields near three isolated buildings with different Height-to-Width ratio using two CFD codes; OpenFOAM, and FLUENT. The results reveal that OpenFOAM is more reliable in simulating PLW fields in twisted wind flows using the new set of boundary conditions. The three-dimensional flow field provided by the OpenFOAM simulation shows sparse streamlines downstream the buildings, indicating lack of organized eddies in the building far wake, which negatively affects the dispersion of air pollutants in twisted winds.


title: A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem)

text: The rapid global spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has created an unprecedented healthcare crisis. The treatment for the severe respiratory illness caused by this virus is primarily symptomatic at this point, although the usage of a broad antiviral drug Remdesivir has been allowed on emergency basis by the Food and Drug Administration (FDA). The ever-increasing death toll highlights an urgent need for development of specific antivirals. In this work, we have utilized docking and simulation methods to identify small molecule inhibitors of SARS-CoV-2 Membrane (M) and Envelope (E) proteins, which are essential for virus assembly and budding. A total of 70 compounds from an Indian medicinal plant source (Azadirachta indica or Neem) were virtually screened against these two proteins and further analyzed with molecular dynamics simulations, which resulted in the identification of a few common compounds with strong binding to both structural proteins. The compounds bind to biologically critical regions of M and E, indicating their potential to inhibit the functionality of these components. We hope that our computational approach may result in the identification of effective inhibitors of SARS-CoV-2 assembly. Communicated by Ramaswamy H. Sarma


title: Changing Role of Nursing Cadre under Emerging Zoonotic Diseases

text: With the launch of new Government of India's initiative Ayushman bharat that envisages conversion of all subcenters into health and wellness centers, the role of nursing professionals in primary health care will be undergoing paradigm shift. Nurses are approximately two-third of the population of health workforce in India. Nurses’ scope of work has widened with additional roles and responsibilities due to shift in the pattern of burden of diseases. The emergence of zoonotic infectious diseases has further enlarged their responsibilities. The main areas, which need attention, are development of nursing workforce, selection and recruitment, placement as per specialization, and preservice and in-service training related to zoonotic surveillance. This article attempts to discuss the role of nurses under emerging zoonotic disease infections.


COVID‐19 precautions: easier said than done when patients are homeless


Porcine Coronavirus HKU15 Detected in 9 US States, 2014


title: Rapid and simple G-quadruplex DNA aptasensor with guanine chemiluminescence detection

text: Abstract Cost-effective and sensitive aptasensor with guanine chemiluminescence detection capable of simply quantifying thrombin in human serum was developed using thrombin aptamer (TBA), one of the G-quadruplex DNA aptamers, without expensive nanoparticles and complicated procedures. Guanines of G-quadruplex TBA-conjugated carboxyfluorescein (6-FAM) bound with thrombin do not react with 3,4,5-trimethoxylphenylglyoxal (TMPG) in the presence of tetra-n-propylammonium hydroxide (TPA), whereas guanines of free TBA- and TBA-conjugated 6-FAM immobilized on the surface of graphene oxide rapidly react with TMPG to emit light. Thus, guanine chemiluminescence in 5% human serum with thrombin was lower than that without thrombin when TBA-conjugated 6-FAM was added in two samples and incubated for 20min. In other words, the brightness of guanine chemiluminescence was quenched due to the formation of G-quadruplex TBA-conjugated 6-FAM bound with thrombin in a sample. High-energy intermediate, capable of emitting dim light by itself, formed from the reaction between guanines of TBA and TMPG in the presence of TPA, transfers energy to 6-FAM to emit bright light based on the principle of chemiluminescence energy transfer (CRET). G-quadruplex TBA aptasensor devised using the rapid interaction between TBA-conjugated 6-FAM and thrombin quantified trace levels of thrombin without complicated procedures. The limit of detection (LOD=background+3×standard deviation) of G-quadruplex TBA aptasensor with good linear calibration curve, accuracy, precision, and recovery was as low as 12.3nM in 5% human serum. Using the technology reported in this research, we expect that various types of G-quadruplex DNA aptasensors capable of specifically sensing a target molecule such as ATP, HIV, ochratoxin, potassium ions, and thrombin can be developed.


title: A review of foal diarrhoea from birth to weaning

text: Diarrhoea is among the most common clinical complaints in foals. Aetiologies, diagnostic testing and recommended interventions for specific causes of enterocolitis are summarised. Many mild to moderately affected foals can be managed in an ambulatory setting, while others will benefit from more intensive care at a referral centre.


title: Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications

text: Lactic acid bacteria (LAB) are promising vectors of choice to deliver active molecules to mucosal tissues. They are recognized as safe by the World Health Organization and some strains have probiotic properties. The wide range of potential applications of LAB-driven mucosal delivery includes control of inflammatory bowel disease, vaccine delivery, and management of auto-immune diseases. Because of this potential, strategies for the display of proteins at the surface of LAB are gaining interest. To display a protein at the surface of LAB, a signal peptide and an anchor domain are necessary. The recombinant protein can be attached to the membrane layer, using a transmembrane anchor or a lipoprotein-anchor, or to the cell wall, by a covalent link using sortase mediated anchoring via the LPXTG motif, or by non-covalent liaisons employing binding domains such as LysM or WxL. Both the stability and functionality of the displayed proteins will be affected by the kind of anchor used. The most commonly surfaced exposed recombinant proteins produced in LAB are antigens and antibodies and the most commonly used LAB are lactococci and lactobacilli. Although it is not necessarily so that surface-display is the preferred localization in all cases, it has been shown that for certain applications, such as delivery of the human papillomavirus E7 antigen, surface-display elicits better biological responses, compared to cytosolic expression or secretion. Recent developments include the display of peptides and proteins targeting host cell receptors, for the purpose of enhancing the interactions between LAB and host. Surface-display technologies have other potential applications, such as degradation of biomass, which is of importance for some potential industrial applications of LAB.


title: Sensitive and Quantitative Detection of Severe Acute Respiratory Syndrome Coronavirus Infection by Real-Time Nested Polymerase Chain Reaction

text: A quantitative, real-time, nested polymerase chain reaction (PCR) method, combining the high sensitivity of nested PCR with time-saving real-time instrumentation, was developed for large-scale screening for severe acute coronavirus (SARS) coronavirus. Forty-six clinical specimens were analyzed by this method, and results were compared with those obtained by conventional, single-round, real-time reverse-transcriptase PCR (RT-PCR) performed in parallel. Of the 17 positive results, 2 identified by our method were not detected by single-round, real-time RT-PCR, which suggests that real-time nested PCR has the potential for increased sensitivity, leading to earlier detection of SARS.


title: Immune complex glomerulonephritis of suspected iatrogenic origin in five Japanese Black calves

text: Five Japanese Black embryo transfer calves from a single embryo flush, 30 to 45-days-old, including 4 live animals for clinical examination and 1 dead for necropsy, were presented with a history of decreased milk intake and hypoproteinemia. Consistent clinicopathological abnormalities in the 4 calves presented for clinical evaluation included hyperkalemia, hyperphosphatemia, hypoproteinemia, hypoalbuminemia, hyperbilirubinemia, increased creatine phosphokinase activity, and proteinuria. Four calves ultimately were necropsied and all had histologic evidence of immune complex glomerulonephritis. Glomerulonephritis in these calves was hypothesized to have resulted from the interaction of passively acquired antibodies at birth and active immunization at 7 and 28 days of age with a Salmonella Typhimurium core antigen vaccine.


Covid-19 — Navigating the Uncharted


docid: xyqlnfzg

title: A follow-up study of children infected with SARS-CoV-2 from western China.

text: Background To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD =7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.


title: Modern clinical microbiology: new challenges and solutions

text: In the twenty-first century, the clinical microbiology laboratory plays a central part in optimizing the management of infectious diseases and surveying local and global epidemiology. This pivotal role is made possible by the adoption of rational sampling, point-of-care tests, extended automation and new technologies, including mass spectrometry for colony identification, real-time genomics for isolate characterization, and versatile and permissive culture systems. When balanced with cost, these developments can improve the workflow and output of clinical microbiology laboratories and, by identifying and characterizing microbial pathogens, provide significant input to scientific discovery. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro3068) contains supplementary material, which is available to authorized users.


Is it about the ‘where’ or thSare ‘how’? Comment on Defining global health as public health somewhere else


title: Potential implications of COVID‐19 on the Canadian pork industry

text: Canada and the US have strong economic ties and form part of an integrated North American pork industry. Canada's pork industry is export‐oriented, and the US represents a key market for both live pigs and pork. Pork value chain stakeholders include input suppliers, pig producers, transportation companies, slaughter plants, wholesalers, and retailers. There are three overriding areas of concern for the Canadian pork industry with respect to potential impacts of the current pandemic (COVID‐19). The first is Canada/US trade and the ability to continue exporting Canadian live pigs and pork to the US. The second is labour and the impact of potential absenteeism on all sectors of the pork value chain. The third is global trade, because Canada's pork industry relies heavily on exporting pork to markets around the world. This article is protected by copyright. All rights reserved


Non–Covid-19 clinical research in the era of pandemic


title: Hospital Associated Respiratory Virus Infection in Children and Adults: It Does Not Just Occur During Cold and Flu Season

text: Hospital-associated respiratory virus infections (HARVI) are an underappreciated source of morbidity and mortality. We examined HARVI incidence and clinical respiratory virus testing practices in a cohort of hospitalized patients with acute respiratory illness. HARVI were identified in patients of all ages, both during and outside of the influenza season.


Veterinary medicine's increasing role in global health


title: COVID‐19 and student nurses: A view from England

text: Jackson et al (2020) have recently described the extraordinary times we face as a result of the Covid-19 pandemic. As we write, the number of cases and the associated mortality continues to rise. In the United Kingdom (UK) a number of 'Nightingale Hospitals' have been constructed within large arenas. Clinical staff who have recently left National Health Service (NHS) are being asked to return to practice to support the rapidly escalating numbers of patients, and nursing students from year two of their degree programme onwards are being asked to opt-in to an extended placement working to further bolster the numbers of care staff available.


title: Host Range and Emerging and Reemerging Pathogens

text: An updated literature survey identified 1,407 recognized species of human pathogen, 58% of which are zoonotic. Of the total, 177 are regarded as emerging or reemerging. Zoonotic pathogens are twice as likely to be in this category as are nonzoonotic pathogens. Emerging and reemerging pathogens are not strongly associated with particular types of nonhuman hosts, but they are most likely to have the broadest host ranges. Emerging and reemerging zoonoses are associated with a wide range of drivers, but changes in land use and agriculture and demographic and societal changes are most commonly cited. However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population.


How COVID-19 is testing and evolving our communication skills


Quality improvement in the time of coronavirus disease 2019 – A change strategy well suited to pandemic response


title: A review of viral diseases of the European wild boar: Effects of population dynamics and reservoir rôle

text: Abstract There has been a worldwide increase in the number and geographical spread of wild boar populations in recent decades leading to an increase in both the circulation of disease agents and greater contact with domestic animals and humans. Diseases affect the population dynamics of wildlife but the effects of most viral diseases on the European wild boar are largely unknown. Many viral diseases present in domestic pig populations are also present in wild boars where they can provide a disease reservoir, as is clearly the case with classical swine fever, but little is known about other viral diseases such as porcine circovirus diseases or hepatitis E. This review considers the current scientific knowledge of the effects of viral diseases on wild boar populations and their rôle as potential disease reservoirs. The focus is on those viral diseases of domestic swine and wild boars that are included as notifiable by the Office International des Epizooties (OIE).


Distant virtual medical education during COVID‐19: Half a loaf of bread


docid: cmjfqkjz

title: Vectored vaccines to protect against PRRSV

text: Abstract PRRSV is the causative agent of the most important infectious disease affecting swine herds worldwide, producing great economic losses. Commercially available vaccines are only partially effective in protection against PRRSV. Moreover, modified live vaccines may allow virus shedding, and could revert generating virulent phenotypes. Therefore, new efficient vaccines are required. Vaccines based on recombinant virus genomes (virus vectored vaccines) against PRRSV could represent a safe alternative for the generation of modified live vaccines. In this paper, current vectored vaccines to protect against PRRSV are revised, including those based on pseudorabies virus, poxvirus, adenovirus, and virus replicons. Special attention has been provided to the use of transmissible gastroenteritis virus (TGEV) as vector for the expression of PRRSV antigens. This vector has the capability of expressing high levels of heterologous genes, is a potent interferon-α inducer, and presents antigens in mucosal surfaces, eliciting both secretory and systemic immunity. A TGEV derived vector (rTGEV) was generated, expressing PRRSV wild type or modified GP5 and M proteins, described as the main inducers of neutralizing antibodies and cellular immune response, respectively. Protection experiments showed that vaccinated animals developed a faster and stronger humoral immune response than the non-vaccinated ones. Partial protection in challenged animals was observed, as vaccinated pigs showed decreased lung damage when compared with the non-vaccinated ones. Nevertheless, the level of neutralizing antibodies was low, what may explain the limited protection observed. Several strategies are proposed to improve current rTGEV vectors expressing PRRSV antigens.


title: 11 Proteomics and Host—Pathogen Interactions A Bright Future?

text: Host–vector–pathogen interactions have been governed since their origin by a subtle balance between attack and transmission strategies and defense mechanisms. Dialogues and conflicts are established between a molecular pathogen and its host and will generate a mutual selection pressure that will result in profound changes in gene expression. In the postgenomic era, proteomics is in its infancy, but represents a promising tool to fill the blanks that still exist in biology despite the sequencing of the genomes of many organisms. In this chapter, we present the interest of proteomics in a better understanding of host–vector–pathogen crosstalks through a synthetic review of the available data generated by proteomics studies, discuss the pitfalls of current approaches, and present new approaches to decipher from molecular interactions to population proteomics leading to biomarkers discovery for diagnosis, therapy, and vaccine purposes.


docid: mhblodgj

title: Covid-19: UK could delay non-urgent care and call doctors back from leave and retirement.


title: Delivery Systems and Local Administration Routes for Therapeutic siRNA

text: With the increasing number of studies proposing new and optimal delivery strategies for the efficacious silencing of gene-related diseases by the local administration of siRNAs, the present review aims to provide a broad overview of the most important and latest developments of non-viral siRNA delivery systems for local administration. Moreover, the main disease targets for the local delivery of siRNA to specific tissues or organs, including the skin, the lung, the eye, the nervous system, the digestive system and the vagina, were explored.


title: Arterivirus nsp4 Antagonizes Interferon Beta Production by Proteolytically Cleaving NEMO at Multiple Sites

text: Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) represent two members of the family Arteriviridae and pose major threats for the horse- and swine-breeding industries worldwide. A previous study suggested that PRRSV nsp4, a 3C-like protease, antagonizes interferon beta (IFN-β) production by cleaving the NF-κB essential modulator (NEMO) at a single site, glutamate 349 (E349). Here, we demonstrated that EAV nsp4 also inhibited virus-induced IFN-β production by targeting NEMO for proteolytic cleavage and that the scission occurred at four sites: E166, E171, glutamine 205 (Q205), and E349. Additionally, we found that, besides the previously reported cleavage site E349 in NEMO, scission by PRRSV nsp4 took place at two additional sites, E166 and E171. These results imply that while cleaving NEMO is a common strategy utilized by EAV and PRRSV nsp4 to antagonize IFN induction, EAV nsp4 adopts a more complex substrate recognition mechanism to target NEMO. By analyzing the abilities of the eight different NEMO fragments resulting from EAV or PRRSV nsp4 scission to induce IFN-β production, we serendipitously found that a NEMO fragment (residues 1 to 349) could activate IFN-β transcription more robustly than full-length NEMO, whereas all other NEMO cleavage products were abrogated for the IFN-β-inducing capacity. Thus, NEMO cleavage at E349 alone may not be sufficient to completely inactivate the IFN response via this signaling adaptor. Altogether, our findings suggest that EAV and PRRSV nsp4 cleave NEMO at multiple sites and that this strategy is critical for disarming the innate immune response for viral survival. IMPORTANCE The arterivirus nsp4-encoded 3C-like protease (3CL(pro)) plays an important role in virus replication and immune evasion, making it an attractive target for antiviral therapeutics. Previous work suggested that PRRSV nsp4 suppresses type I IFN production by cleaving NEMO at a single site. In contrast, the present study demonstrates that both EAV and PRRSV nsp4 cleave NEMO at multiple sites and that this strategy is essential for disruption of type I IFN production. Moreover, we reveal that EAV nsp4 also cleaves NEMO at glutamine 205 (Q205), which is not targeted by PRRSV nsp4. Notably, targeting a glutamine in NEMO for cleavage has been observed only with picornavirus 3C proteases (3C(pro)) and coronavirus 3CL(pro). In aggregate, our work expands knowledge of the innate immune evasion mechanisms associated with NEMO cleavage by arterivirus nsp4 and describes a novel substrate recognition characteristic of EAV nsp4.


Letter: Neurosurgery at war with the COVID-19 pandemic: patient’s management from an African neurosurgical center


title: Mathematical Modeling of Severe Acute Respiratory Syndrome Nosocomial Transmission in Japan: The Dynamics of Incident Cases and Prevalent Cases

text: An outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Hong Kong in late February 2003, resulting in 8,096 cumulative cases with 774 deaths. The outbreak was amplified by nosocomial transmission in many hospitals. Using mathematical modeling, we simulated the number of new incident and prevalent cases of SARS after one infected person was admitted to a hospital (index case). The simulation was tested stochastically using the SEIR model based on previously reported Gamma distributions. We estimated the duration time until 10 beds in negative pressure rooms in Chiyoda‐ku, one of the 23 wards in Tokyo, were fully occupied with SARS‐infected patients. We determined the impact of an increasing number of days on the number of prevalent cases until the index case was isolated. The prevalent cases increase exponentially along with the increase of the non‐isolation period of the index case, and all the beds were fully occupied if the index case was not isolated until more than 6 days. However even 2 days non‐isolation period of the index case could fill up all the beds when 16% of secondary infections are transmitted outside the hospital. There is a possibility that an epidemic will occur with the isolation of the index case even at early days if the infection is transmitted outside the hospital. The simulation results revealed that it was important to recognize and isolate SARS patients as early as possible and also to prevent the transmission spreading outside the hospital to control an epidemic.


docid: tpdltxas

title: Q fever—the superstition of avoiding the word “quiet” as a coping mechanism: randomised controlled non-inferiority trial

text: OBJECTIVE: To determine the validity of the superstition that utterance of the word “quiet” in a clinical setting increases workload. DESIGN: Prospective randomised controlled non-inferiority study. SETTING: Microbiology department of a large teaching hospital in Lancashire, UK. PARTICIPANTS: Two members of the medical microbiology team carried out the duty work on any given week day and an on-call team member on any weekend day. 29 days were assigned in which staff were to say “Today will be a quiet day” and 32 days were assigned in which staff were to refrain from saying the word “quiet” in any context. INTERVENTIONS: Each day was randomly allocated to either saying “Today will be a quiet day” (intervention group) or refraining from saying the word “quiet” (control group) in any context. MAIN OUTCOME MEASURES: The primary outcome was mean overall workload: a composite of number of clinically related telephone calls, clinically significant results, or validated results processed by the duty medical microbiology team during a 24 hour period referred to collectively as “clinical episodes.” A difference of 30 clinical episodes was considered as the margin of non-inferiority. Secondary outcomes included the individual components of the primary outcome. RESULTS: Workload was measured each day over a 61 day period (1 May to 30 June 2019). A mean 139.0 clinical episodes occurred on control days compared with 144.9 on days when the experimental intervention was uttered, a difference of 5.9 (95% confidence interval−12.9 to 24.7). The upper bound was less than the specified margin of 30, providing evidence for non-inferiority. No evidence of a difference in workload was found between interventions with any of the four components, whether considering unadjusted or adjusted analyses, or looking at the subgroups of week days or weekends. CONCLUSIONS: The study findings refute the long held superstition that utterance of the word “quiet” impacts on clinical workload, and therefore it should not be avoided. In the era of considerable staff shortages and increased work related stress, doctors should look to other methods to increase resilience and protect their wellbeing and mental health. TRIAL REGISTRATION: Lancashire Teaching Hospitals NHS Foundation Trust’s research department SE-259.


title: Outrunning Burnout in a GI Fellowship Program During the COVID-19 Pandemic

text: Many GI training programs have needed to adjust to the serious disruption to the training and education of fellows worldwide due to the COVID-19 pandemic. A silent problem that has arisen within programs is the issue of burnout among their trainees. Burnout is common among gastroenterologists, especially in fellows (Keswani et al. in Gastroenterology 147(1):11–14, 2014. 10.1053/j.gastro.2014.05.023, Am J Gastroenterol 106(10):1734–1740, 2011. 10.1038/ajg.2011.148), with negative consequences to patient care and the safety of the trainees if not effectively dealt with. In this article, the author describes several additional factors potentially contributing to the intensifying burnout of the fellows in their home institution during this pandemic. Moreover, he describes specific practical interventions that the hospital and program have taken in order to address these factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10620-020-06401-4) contains supplementary material, which is available to authorized users.


title: Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans

text: A method of 3-amino-4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]furazan synthesis was optimized. Condensation of these compounds with 2,5-dimethoxytetrahydrofuran resulted in a series of previously unknown 4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]-3-(pyrrol-1-yl)furazans. All target compounds were evaluated for both antimitotic microtubule destabilizing effect in a phenotypic sea urchin embryo assay and cytotoxicity in a panel of 60 human cancer cell lines. Pyrrolyl derivatives of triazolylfurazans were determined as antiproliferative compounds. The most potent microtubule targeting compounds 7a and 7e are of interest for further trials as antineoplastic agents.


Vacunas contra el coronavirus


Cromolyns: treatment for the common cold?


title: Clinical review: SARS – lessons in disaster management

text: Disaster management plans have traditionally been required to manage major traumatic events that create a large number of victims. Infectious diseases, whether they be natural (e.g. SARS [severe acute respiratory syndrome] and influenza) or the result of bioterrorism, have the potential to create a large influx of critically ill into our already strained hospital systems. With proper planning, hospitals, health care workers and our health care systems can be better prepared to deal with such an eventuality. This review explores the Toronto critical care experience of coping in the SARS outbreak disaster. Our health care system and, in particular, our critical care system were unprepared for this event, and as a result the impact that SARS had was worse than it could have been. Nonetheless, we were able to organize a response rapidly during the outbreak. By describing our successes and failures, we hope to help others to learn and avoid the problems we encountered as they develop their own disaster management plans in anticipation of similar future situations.


title: Immunotherapy could help against new coronavirus

text: The new respiratory virus which emerged in the Middle East last year could be pegged back by artificially boosting the body's immune response


title: Targeting ADP-ribosylation as an antimicrobial strategy

text: Abstract ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.


title: Identification and genome characterization of a novel feline picornavirus proposed in the Hunnivirus genus

text: Abstract The genus Hunnivirus, which has been identified in sheep, cattle, and rats, was first proposed in the family Picornaviridae by the International Committee on Taxonomy of Viruses in 2013. In this study, a hunnivirus was detected in fecal samples collected from a diarrheic cat in Southern China in 2017. Genome sequencing and analysis indicated that the novel hunnivirus has the same genome organization as reported for other hunniviruses, 5′UTR-L-P1(VP4-VP2-VP3-VP1)-P2(2A-2B-2C)-P3(3A-3B-3Cpro-3Dpol)-3′UTR, but is genetically divergent. This hunnivirus is proposed as a novel genotype of the species Hunnivirus A and provisionally designated feline hunnivirus. Our study expands the host range of hunnivirus and enriches knowledge on picornaviruses.


title: Development of an anti-ferret CD4 monoclonal antibody for the characterisation of ferret T lymphocytes

text: Abstract The ferret is an established animal model for a number of human respiratory viral infections, such as influenza virus and more recently, Ebola virus. However, a paucity of immunological reagents has hampered the study of cellular immune responses. Here we describe the development and characterisation of a novel monoclonal antibody (mAb) against the ferret CD4 antigen and the characterisation of ferret CD4 T lymphocytes. Recombinant production and purification of the ferret CD4 ectodomain soluble protein allowed hybridoma generation and the generation of a mAb (FeCD4) showing strong binding to ferret CD4 protein and lymphoid cells by flow cytometry. FeCD4 bound to its cognate antigen post-fixation with paraformaldehyde (PFA) which is routinely used to inactivate highly pathogenic viruses. We have also used FeCD4 in conjunction with other immune cell markers to characterise ferret T cells in both primary and secondary lymphoid organs. In summary, we have developed an important reagent for the study of cellular immunological responses in the ferret model of infectious disease.


title: Chapter Three Epidemiology and Biostatistics

text: Abstract Epidemiology and biostatistics are the cornerstone of public health and preventive medicine. These practices use mathematical, scientific, and social methods to monitor disease trends and provide intervention to prevent future disease. [147 questions.]


title: Environmental Health and Bioterrorism

text: Biological warfare has complex and permanent impact on the environment in comparison to other war types (conventional, nuclear, or chemical). However, changes in the environment interfere with many of the major determinants of biological warfare (bioterrorism - biological attack). Four components are required for a biological attack: perpetrators, agents, mediums/means of delivery, and targets. Environmental changes caused by humans (auto-bioterrorism) and bioterrorism-related diseases they may impact are urbanization, agricultural intensification, de(re)forestation, water projects, and climate changes. Agroterrorism implies deliberate attack against commercial crops or livestock population. Agroterrorism is a multidimensional threat, involving a wide range of motives and perpetrators, and encompassing a wide range of actions, from single act of sabotage to strategic wartime programs with potentially disastrous spill-over' effects on susceptible wildlife and endangered species population. The threat of an agroterrorist attack depends on motivations and technical requirements of agroterrorism. Technical barriers to agroterrorism are lower than these to human-targeted bioterrorism. Terrorists' motives vary widely. The two most common are the profit motive and the anti-GMO (genetically modified organism) motive. The threat of an agroterrorist attack can be countered at four levels: (1) at the organism level, through animal or plant disease resistance; (2) at the farm level, through facility management techniques designed to prevent disease introduction or transmission; (3) at the agricultural sector level, through disease detection and response procedures; (4) at the national level, through policies designed to minimize the social and economic costs of a catastrophic disease outbreak.


docid: qsjzujnc

title: Improving market performance in the digital economy

text: Abstract The digital economy has substantially reduced market frictions but also posed new challenges for the efficient functioning of markets. In particular, the drastic reductions in the costs of search, entry, transportation, and reproduction have profound implications for the role of platforms, the value of innovation, and the balance between firms' data needs and consumer privacy. I review some recent economic research that sheds light on these issues, and discuss how well-designed policies on competition, regulation, IP protection, and consumer privacy can improve market performance in the digital economy.


title: Acute Myelitis as a Neurological Complication ofCovid-19:A Case Report and MRI Findings

text: During the recent outbreak of COVID-19 caused by SARS-CoV-2 coronavirus, there is rising concerns about neurological complications of COVID-19. Fever, headache and anosmia may occur early during the disease course. Other neurological sequalae such as encephalitis may occur in later phases. We report a case of acute myelitis in a 32 year old male Covid-19 positive patient who presented with a two-day history of flu-like symptoms then sudden onset paraplegia and urinary retention. The incidence is not known and the pathogenesis of the disease behind this manifestation is still not fully understood. Nevertheless considering the broad differential diagnosis of acute myelitis, prompt clinical and diagnostic work up was crucial to exclude other causes. Patients presenting with neurological symptoms such as loss of consciousness, ataxia, convulsions, status epilepticus, encephalitis, myelitis or neuritis should raise concerns for Covid-19 infection during this pandemic prompting early diagnosis and initiation of proper management.


title: Ultrasensitive haptoglobin biomarker detection based on amplified chemiluminescence of magnetite nanoparticles

text: BACKGROUND: Haptoglobin is an acute-phase protein used as predicting diagnostic biomarker both in humans (i.e., diabetes, ovarian cancer, some neurological and cardiovascular disorders) and in animals (e.g., bovine mastitis). The latter is a frequent disease of dairy industry with staggering economical losses upon decreased milk production and increased health care costs. Early stage diagnosis of the associated diseases or inflammation onset is almost impossible by conventional analytical manners. RESULTS: The present study demonstrates a simple, rapid, and cost-effective label-free chemiluminescence bioassay based on magnetite nanoparticles (MNPs) for sensitive detection of haptoglobin by employing the specific interaction of hemoglobin-modified MNPs. The resulting haptoglobin-hemoglobin complex inhibits the peroxidase-like activity of luminol/H(2)O(2)-hemoglobin-MNPs sensing scheme and reduces the chemiluminescence intensities correspondingly to the innate haptoglobin concentrations. Quantitative detection of bovine haptoglobin was obtained within the range of 1 pg mL(−1) to 1 µg mL(−1), while presenting 0.89 pg mL(−1) limit of detection. Moreover, the influence of causative pathogenic bacteria (i.e., Streptococcus dysgalactiae and Escherichia coli) and somatic cell counts (depicting healthy, sub-clinical and clinical mastitis) on the emitted chemiluminescence radiation were established. The presented bioassay quantitative performances correspond with a standardized assay kit in differentiating dissimilar milk qualities. CONCLUSIONS: Overall, the main advantage of the presented sensing concept is the ability to detect haptoglobin, at clinically relevant concentrations within real milk samples for early bio-diagnostic detection of mastitis and hence adjusting the precise treatment, potentially initiating a positive influence on animals’ individual health and hence on dairy farms economy.


title: Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection

text: In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome.


title: Mucin 4 Protects Female Mice from Coronavirus Pathogenesis

text: Using incipient lines of the Collaborative Cross (CC), a murine genetic reference population, we previously identified a quantitative trait loci (QTL) associated with low SARS-CoV titer. In this study, we integrated sequence information and RNA expression of genes within the QTL to identify mucin 4 (Muc4) as a high priority candidate for controlling SARS-CoV titer in the lung. To test this hypothesis, we infected Muc4-/- mice and found that female, but not male, Muc4-/- mice developed more weight loss and disease following infection with SARS-CoV. Female Muc4-/- mice also had more difficulty breathing despite reduced lung pathology; however, no change in viral titers was observed. Comparing across viral families, studies with chikungunya virus, a mosquito-borne arthralgic virus, suggests that Muc4’s impact on viral pathogenesis may be widespread. Although not confirming the original titer QTL, our data identifies a role for Muc4 in the SARS-CoV disease and viral pathogenesis. Importance Given the recent emergence of SARS-CoV-2, this work suggest that Muc4 expression plays a protective role in female mice not conserved in male mice following SARS-CoV infection. With the SARS-CoV-2 outbreak continuing, treatments that modulate or enhance Muc4 activity may provide an avenue for treatment and improved outcomes. In addition, the work highlights the importance of studying host factors including host genetics and biological sex as key parameters influencing infection and disease outcomes.


title: A pandemic risk assessment of middle east respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia

text: Since the initial emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, a high incidence rate has been observed in Saudi Arabia. This suggests that the country is at continuous risk. The epidemic level of MERS-CoV infection was examined in Saudi Arabia by the Susceptible-Infectious-Recovered (SIR) model using a Bayesian approach for estimation of time dependent reproduction number (R) across a two-year interval (May, 2013-May, 2015) in five defined clusters, followed by sensitivity analysis of the most significant clusters. Significant MERS-CoV peaks were detected in the period between March and May of each year. Moreover, MERS-CoV infection was highlighted in western (40.8%) and central (31.9%) regions, followed by eastern region (20%). The temporal-based Bayesian approach indicated a sub-critical epidemic in all regions in the baseline scenario (R: 0.85–0.97). However, R potential limit was exceeded in the sensitivity analysis scenario in only central and western regions (R: 1.08–1.12) that denoted epidemic level in those regions. The impact of sporadic cases was found relatively insignificant and pinpointed to the lack of zoonotic influence on MERS-CoV transmission dynamics. The results of current study would be helpful for evaluation of future progression of MERS-CoV infections, better understanding and control interventions.


title: Diarrhées néonatales à rotavirus résultats d'une enquête conduite dans des unités de néonatologie

text: Summary A retrospective survey was performed among 24 neonatal care units. In the years 1989–1990, outbreaks of rotavirus infections were observed in 58 % and recurred in 46 % of neonatal care units. Six units presented with 3 or more outbreaks. Rapid diagnosis methods always were available and were usually agglutination latex test or ELISA test. Measures were suggested to limit the spread of the outbreaks : wearing of a gown ascribed to each infant (20/0) ; isolation of infected neonates (16/3) ; cohorting infected neonates (11/7) ; systematic stool examination for rotavirus identification in all neonates (9/10) ; use of gloves for handling contaminated stools (6/13). Stopping admissions and systematic stools examination in staff members were never applied.


title: 病毒性肺炎的流行对肺癌患者的影响和思考

text: The worldwide epidemic of three coronaviruses and one influenza virus in 21(st) century have seriously threatened human health. Infection with these viruses can cause respiratory symptoms. The patients with lung cancer are more susceptible to viral infection and have a worse prognosis due to the advanced age and the systemic immunosuppressive state caused by malignancy itself and the anticancer treatments. In addition, without sufficient clinical awareness, a missed diagnosis of viral pneumonia may occur due to the fever and respiratory symptoms caused by lung cancer and its secondary diseases. Furthermore, control measures against viral outbreaks may interfere with routine diagnosis and treatment of lung cancer patients. Therefore, scientific protection and individualized management of lung cancer patients are particularly important during virus epidemic prevention and control. Here, we systematically reviewed the epidemiological and clinical characteristics of viral pneumonia, its impact on patients with lung cancer and the differential diagnosis of lung cancer-related respiratory manifestations, aiming to provide guidance for the individual management of lung cancer patients during the prevention and control of viral pneumonia epidemic.


title: Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome

text: BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. METHODS: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. RESULTS: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). CONCLUSION: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm.


The role of telemedicine during the COVID-19 epidemic in China—experience from Shandong province


title: Niclosamide, a Drug with Many (Re)purposes

text: Niclosamide is an anthelmintic drug that has been used for over 50 years mainly to treat tapeworm infections. However, with the increase in drug repurposing initiatives, niclosamide has emerged as a true hit in many screens against various diseases. Indeed, from being an anthelmintic drug, it has now shown potential in treating Parkinson's disease, diabetes, viral and microbial infections, as well as various cancers. Such diverse pharmacological activities are a result of niclosamide's ability to uncouple mitochondrial phosphorylation and modulate a selection of signaling pathways, such as Wnt/β‐catenin, mTOR and JAK/STAT3, which are implicated in many diseases. In this highlight, we discuss the plethora of diseases that niclosamide has shown promise in treating.


title: A double epidemic model for the SARS propagation

text: BACKGROUND: An epidemic of a Severe Acute Respiratory Syndrome (SARS) caused by a new coronavirus has spread from the Guangdong province to the rest of China and to the world, with a puzzling contagion behavior. It is important both for predicting the future of the present outbreak and for implementing effective prophylactic measures, to identify the causes of this behavior. RESULTS: In this report, we show first that the standard Susceptible-Infected-Removed (SIR) model cannot account for the patterns observed in various regions where the disease spread. We develop a model involving two superimposed epidemics to study the recent spread of the SARS in Hong Kong and in the region. We explore the situation where these epidemics may be caused either by a virus and one or several mutants that changed its tropism, or by two unrelated viruses. This has important consequences for the future: the innocuous epidemic might still be there and generate, from time to time, variants that would have properties similar to those of SARS. CONCLUSION: We find that, in order to reconcile the existing data and the spread of the disease, it is convenient to suggest that a first milder outbreak protected against the SARS. Regions that had not seen the first epidemic, or that were affected simultaneously with the SARS suffered much more, with a very high percentage of persons affected. We also find regions where the data appear to be inconsistent, suggesting that they are incomplete or do not reflect an appropriate identification of SARS patients. Finally, we could, within the framework of the model, fix limits to the future development of the epidemic, allowing us to identify landmarks that may be useful to set up a monitoring system to follow the evolution of the epidemic. The model also suggests that there might exist a SARS precursor in a large reservoir, prompting for implementation of precautionary measures when the weather cools down.


title: Antibacterial Discovery: 21st Century Challenges

text: It has been nearly 50 years since the golden age of antibiotic discovery (1945–1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.