title: Multidisciplinary approach to COVID-19 and cancer: consensus from scientific societies in Argentina

text: INTRODUCTION: The world is living through an outbreak of an acute respiratory syndrome caused by a new betacoronavirus known as coronavirus 2 (SARS CoV-2), which has been declared an international public health emergency by the World Health Organisation. Cancer patients are a very special population in this setting since they are more susceptible to viral infections than the general population. Several recommendations have been made on this issue, most of them based on expert opinion and institutional experience. It is essential to gather the evidence available for decision making. OBJECTIVE: To review the evidence available in order to create a multi-institutional position from the perspective of scientific societies in Argentina involved in the management of cancer patients. METHODOLOGY: The review included two phases: 1) search and systematic revision of the medical literature; 2) consensus and revision of the document drafted by national scientific societies involved in the management and care of cancer patients using the modified Delphi method. The final results were presented at a videoconference with all the participants. Also, additional comment and recommendations were discussed. The final document was revised and approved for publication by the members of the panel. RESULTS: The consensus panel included 18 representatives from scientific societies from Argentina who assessed the evidence and then made recommendations for the management of cancer patients in our country. International guidelines (CDC; ASCO, NCCN and ESMO) were considered as a background for analysis, as well as institutional guidelines and an open ad hoc survey administered to 114 healthcare professionals from the scientific societies involved in this study. The recommendations are grouped as follows: 1) general care interventions—training of the personnel, cleaning and disinfection of the hospital premises and patient scheduling; 2) treatment decisions—patient care, surgeries, immunosuppressive therapy, radiotherapy and screening; 3) ethical considerations—optimisation of resources, end-of-life care for critically-ill patients; 4) management of hospitalised patients; and 5) wellbeing of the healthcare team. The general recommendation arising from the study is that the management of cancer patients must adapt to the exceptional pandemic status quo without disregarding treatment or cure options. Moreover, healthcare professional accompaniment of all patients should not be neglected. All healthcare professionals must make a significant joint effort to create multidisciplinary teams to discuss the most appropriate measures for each particular situation. CONCLUSIONS: The scientific evidence available on this topic worldwide is in progress. This together with the epidemiologically shifting scenario poses unprecedented challenges in the management of cancer amidst this global pandemic. Furthermore, the key role of the healthcare structural organisation appears evident, such as the drafting of clear guidelines for all the stakeholders, adaptability to constant change and an interdisciplinary shared vision through consensus to provide adequate care to our cancer patients in the light of uncertainty and fast-paced change.


title: 16S rRNA gene sequencing reveals an altered composition of the gut microbiota in chickens infected with a nephropathogenic infectious bronchitis virus

text: Infectious bronchitis virus (IBV), a member of the Coronaviridae family, causes serious losses to the poultry industry. Intestinal microbiota play an important role in chicken health and contribute to the defence against colonization by invading pathogens. The aim of this study was to investigate the link between the intestinal microbiome and nephropathogenic IBV (NIBV) infection. Initially, chickens were randomly distributed into 2 groups: the normal group (INC) and the infected group (IIBV). The ilea were collected for morphological assessment, and the ileal contents were collected for 16S rRNA gene sequencing analysis. The results of the IIBV group analyses showed a significant decrease in the ratio of villus height to crypt depth (P < 0.05), while the goblet cells increased compared to those in the INC group. Furthermore, the microbial diversity in the ilea decreased and overrepresentation of Enterobacteriaceae and underrepresentation of Chloroplast and Clostridia was found in the NIBV-infected chickens. In conclusion, these results showed that the significant separation of the two groups and the characterization of the gut microbiome profiles of the chickens with NIBV infection may provide valuable information and promising biomarkers for the diagnosis of this disease.


title: Chapter 26 Quarantine facilities and operations

text: Publisher Summary This chapter focuses on quarantine requirements at animal facilities. The well-established quarantine measures for nonhuman primates and those that have re-emerged for rodents are very important. The increased use and exchange of genetically engineered mutant mice especially demands rodent quarantine capabilities for the majority of research institutions. Apart from species-specific housing requirements, it is important to consider pathogens to be contained in terms of the route of transmission, and degree of hazard to human and animal health. Animals obtained from commercial vendors, as opposed to other research institutions, may be less likely to harbor undesirable microorganisms, often allowing them to be exempt from a quarantine program. The ideal quarantine facility should be flexible enough to allow the use of multiple species, and take into account the number and frequency of shipments expected. The more shipments and different species involved, the more subdivided the facility should be, through the use of multiple rooms, cubicles, isolators, etc. At a minimum, ABSL2 design criteria should be used to enable the containment of pathogens at the room or cage level, while also preventing agent transmission via contaminated animal waste, fomites, and personnel.


title: Food as medicine: a possible preventive measure against coronavirus disease (COVID‐19)

text: The recent and ongoing outbreak of coronavirus disease (COVID‐19) is a huge global challenge. The outbreak, which first occurred in Wuhan City, Hubei Province, China and then rapidly spread to other provinces and to more than 200 countries abroad, has been declared a global pandemic by the World Health Organization (WHO). Those with compromised immune systems and/or existing respiratory, metabolic or cardiac problems are more susceptible to the infection and are at higher risk of serious illness or even death. The present review was designed to report important functional food plants with immunomodulatory and anti‐viral properties. Data on medicinal food plants was retrieved and downloaded from English‐language journals using online search engines. The functional food plants herein documented might not only enhance the immune system and cure respiratory tract infections but can also greatly impact the overall health of the general public. As many people in the world are now confined to their homes, inclusion of these easily accessible plants in the daily diet may help to strengthen the immune system and guard against infection by SARS‐CoV‐2. This might reduce the risk of COVID‐19 and initiate a rapid recovery in cases of SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency

text: Abstract According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodríguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.


title: Bovine Coronavirus Associated Syndromes

text: Bovine coronaviruses, like other animal coronaviruses, have a predilection for intestinal and respiratory tracts. The viruses responsible for enteric and respiratory symptoms are closely related antigenically and genetically. Only 4 bovine coronavirus isolates have been completely sequenced and thus, the information about the genetics of the virus is still limited. This article reviews the clinical syndromes associated with bovine coronavirus, including pneumonia in calves and adult cattle, calf diarrhea, and winter dysentery; diagnostic methods; prevention using vaccination; and treatment, with adjunctive immunotherapy.


title: Chapter 35 The Chinese or Striped-Back Hamster

text: The Chinese hamster, also known as the striped-back or gray hamster, is indigenous to Northern Asia. Its small size, polyestrous cycle, short gestation period, and low chromosome number are among the biological attributes that have made it an invaluable laboratory animal for biomedical research. The Chinese hamster first played a role in infectious disease research to type pneumococci strains. It was subsequently used in a variety of infectious disease and epidemiological studies. With early attempts at inbreeding, a hereditary form of diabetes mellitus was identified in the species. The Chinese hamster subsequently became a useful tool for characterizing the metabolic disorder and developing therapies for the human disease. Due to its low chromosome number, Chinese hamster tissue cultures have been a popular research tool for mutagenicity and carcinogenicity studies. During the past 20 years, Chinese hamster ovary (CHO) cells have been utilized to synthesize a wide array of recombinant protein products. Therapeutic proteins derived from CHO cells are currently used to treat numerous human diseases.


title: Genetic control of alphavirus pathogenesis

text: Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors expand into new geographic ranges. Members of the alphavirus genus tend to induce clinical disease characterized by rash, arthralgia, and arthritis (chikungunya virus, Ross River virus, and Semliki Forest virus) or encephalomyelitis (eastern equine encephalitis virus, western equine encephalitis virus, and Venezuelan equine encephalitis virus), though some patients who recover from the initial acute illness may develop long-term sequelae, regardless of the specific infecting virus. Studies examining the natural disease course in humans and experimental infection in cell culture and animal models reveal that host genetics play a major role in influencing susceptibility to infection and severity of clinical disease. Genome-wide genetic screens, including loss of function screens, microarrays, RNA-sequencing, and candidate gene studies, have further elucidated the role host genetics play in the response to virus infection, with the immune response being found in particular to majorly influence the outcome. This review describes the current knowledge of the mechanisms by which host genetic factors influence alphavirus pathogenesis and discusses emerging technologies that are poised to increase our understanding of the complex interplay between viral and host genetics on disease susceptibility and clinical outcome.


title: On the Quarantine Period for Ebola Virus

text: Background: 21 days has been regarded as the appropriate quarantine period for holding individuals potentially exposed to Ebola Virus (EV) to reduce risk of contagion. There does not appear to be a systematic discussion of the basis for this period. Methods: The prior estimates for incubation time to EV were examined, along with data on the first 9 months of the current outbreak. These provided estimates of the distribution of incubation times. Results: A 21 day period for quarantine may result in the release of individuals with a 0.2 - 12% risk of release prior to full opportunity for the incubation to proceed. It is suggested that a detailed cost-benefit assessment, including considering full transmission risks, needs to occur in order to determine the appropriate quarantine period for potentially exposed individuals.


title: SARS‐associated viral hepatitis caused by a novel coronavirus: Report of three cases

text: Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (Hepatology 2004;39:302–310.)


title: Pandemic influenza: are we prepared to face our obligations?

text: After decades of low personal risk for contracting lethal diseases, physicians are suddenly facing the possibility of a substantial increase in occupational risk during an influenza pandemic. If they are not confronted before the onset of an influenza pandemic, feelings of unease and fear or ignorance about physicians' professional obligations could profoundly hinder individual physicians in fulfilling their professional duties. Such feelings could therefore undermine institutional and societal preparations. In their review published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic.


title: Rotavirus infection induces G1 to S phase transition in MA104 cells via Ca+2/Calmodulin pathway

text: Abstract Viruses, obligate cellular parasites rely on host cellular functions and target the host cell cycle for their own benefit. In this study, effect of rotavirus infection on cell cycle machinery was explored. We found that rotavirus (RV) infection in MA104 cells induces the expression of cyclins and cyclin dependent kinases and down-regulates expression of CDK inhibitors, resulting in G1 to S phase transition. The rotavirus induced S phase accumulation was found to be concurrent with induction in expression of calmodulin and activation of CaMKI which is reported as inducer of G1–S phase transition. This cell cycle manipulation was found to be Ca+2/Calmodulin pathway dependent. The physiological relevance of G1 to S phase transition was established when viral gene expressions as well as viral titers were found to be increased in S phase synchronized cells and decreased in G0/G1 phase synchronized cells compared to unsynchronized cells during rotavirus infection.


¿Se ha hecho un uso más racional de los servicios de urgencias oftalmológicas ante la pandemia por COVID-19?


title: Ebola: a call to action

text: The size, speed and potential reach of the 2014 Ebola virus outbreak in West Africa presents a wake-up call to the research and pharmaceutical communities—and to federal governments—of the continuing need to invest resources in the study and cure of emerging infectious diseases.


title: NMR Structure of the SARS Coronavirus Nonstructural Protein 7 in Solution at pH 6.5

text: The NMR structure of the severe acute respiratory syndrome coronavirus (SARS-CoV) non-structural protein 7 (nsp7) in aqueous solution at pH 6.5 was determined and compared with the results of previous structure determinations of nsp7 in solution at pH 7.5 and in crystals of a hexadecameric nsp7/nsp8 complex obtained from a solution at pH 7.5. All three structures contain four helices as the only regular secondary structures, but there are differences in the lengths and sequence locations of the four helices, as well as between the tertiary folds. The present study includes data on conformational equilibria and intramolecular rate processes in nsp7 in solution at pH 6.5, which provides further insights into the polymorphisms implicated by comparison of the presently available three nsp7 structures.


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title: Membrane proteins of arterivirus particles: Structure, topology, processing and function

text: Abstract Arteriviruses, such as equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV), are important pathogens in veterinary medicine. Despite their limited genome size, arterivirus particles contain a multitude of membrane proteins, the Gp5/M and the Gp2/3/4 complex, the small and hydrophobic E protein and the ORF5a protein. Their function during virus entry and budding is understood only incompletely. We summarize current knowledge of their primary structure, membrane topology, (co-translational) processing and intracellular targeting to membranes of the exocytic pathway, which are the budding site. We profoundly describe experimental data that led to widely believed conceptions about the function of these proteins and also report new results about processing steps for each glycoprotein. Further, we depict the location and characteristics of epitopes in the membrane proteins since the late appearance of neutralizing antibodies may lead to persistence, a characteristic hallmark of arterivirus infection. Some molecular features of the arteriviral proteins are rare or even unique from a cell biological point of view, particularly the prevention of signal peptide cleavage by co-translational glycosylation, discovered in EAV-Gp3, and the efficient use of overlapping sequons for glycosylation. This article reviews the molecular mechanisms of these cellular processes. Based on this, we present hypotheses on the structure and variability of arteriviral membrane proteins and their role during virus entry and budding.


title: The Novel Coronavirus SARS‐CoV‐2: From a Zoonotic Infection to Coronavirus Disease‐19 (COVID19)

text: OBJECTIVE: The novel coronavirus, SARS‐CoV‐2 is an international public health emergency. Until now, the intermediate host and mechanisms of interspecies jump of this virus are unknown. METHODS: Phylogenetic analysis of all available bat coronavirus (CoV) complete genomes was performed in order to analyze the relationships between bat CoV and SARS‐CoV‐2. In order to suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals which were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions which may have permitted the adaptation of SARS‐CoV‐2 to the human host. RESULTS: The phylogenetic analysis demonstrated that SARS‐CoV‐2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS‐CoV‐2, bat RaTG13 and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS‐CoV‐2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS‐CoV‐2 tropism to human cells. CONCLUSIONS: Our analysis shows the tight relationship between SARS‐CoV‐2 and bat SARS‐like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function. This article is protected by copyright. All rights reserved.


docid: glogkvqb

title: Pandemic Influenza Threat and Preparedness

text: The threat of a human influenza pandemic has greatly increased over the past several years with the emergence of highly virulent avian influenza viruses, notably H5N1 viruses, which have infected humans in several Asian and European countries. Previous influenza pandemics have arrived with little or no warning, but the current widespread circulation of H5N1 viruses among avian populations and their potential for increased transmission to humans and other mammalian species may afford us an unprecedented opportunity to prepare for the next pandemic threat. The US Department of Health and Human Services is coordinating a national strategy to respond to an influenza pandemic that involves multiple agencies, including the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health (NIH). Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) conducts basic and clinical research to develop new vaccine technologies and antiviral drugs against influenza viruses. We describe recent research progress in preparing for pandemic influenza.


title: Therapeutic approach to respiratory infections in lung transplantation

text: Abstract Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation.


title: The examination of sleep quality for frontline healthcare workers during the outbreak of COVID-19

text: PURPOSE: Few studies have addressed the sleep disturbances of healthcare workers during crisis events of public health. This study aimed to examine the sleep quality of frontline healthcare workers (FLHCW) in Bahrain during the COVID-19 pandemic, and compare it with the sleep quality of non-frontline healthcare workers (NFLHCW). METHODS: Healthcare workers (n = 280) from multiple facilities belonging to the Ministry of Health, Bahrain, were invited to participate in this cross-sectional study. An online questionnaire, including socio-demographics, the Pittsburgh Sleep Quality Index (PSQI), and the Perceived Stress Scale (PSS), was used to evaluate sleep disturbances and stress levels of healthcare workers. Poor sleep quality was defined as PSQI ≥ 5 and moderate-severe stress as PSS ≥ 14. Descriptive statistics were used to compare the scores of FLHCW and NFLHCW. Univariate and multivariate binary logistic regressions were used to identify predictors of poor sleep quality, moderate-severe stress, and the combined problem of poor sleep quality and moderate-severe stress. RESULTS: A total of 257 participants (129 FLHCW and 128 NFLHCW) provided usable responses. The overall PSQI and PSS scores were 7.0 ± 3.3 and 20.2 ± 7.1, respectively. The FLHCW scored higher in the PSQI and PSS compared with the NFLHCW; however, the differences in the PSQI and PSS scores were not statistically significant. For the FLHCW, 75% were poor sleepers, 85% had moderate-severe stress, and 61% had both poor sleep quality and moderate-severe stress. For the NFLHCW, 76% were poor sleepers, 84% had moderate-severe stress, and 62% had both poor sleep quality and moderate-severe stress. Female sex and professional background were the predictors of poor sleep quality and stress. CONCLUSIONS: Poor sleep quality and stress are common during the COVID-19 crisis. Approximately, 60% of both FLHCW and NFLHCW have poor sleep quality combined with moderate-severe stress.


title: The role of infection in asthma

text: Abstract This paper reviews the impact of infections on the onset and clinical course of bronchial asthma. A just emphasis is given to the role viral infections, particularly rhinovirus infections, play in exacerbations, and that played by respiratory syncytial virus, suspected of triggering the asthmatic syndrome. The mechanisms of the immune response to virus attacks are explained, highlighting the asthmatic and allergic patient's weakened response, particularly in the perinatal period. Further stressed is a potentiating effect of viral aggression on the allergic response. The hygiene hypothesis and its lack of scientific consistency is detailed, at least as far as the role it seeks to confer on an unproven antagonism of the Th1 and Th2 lymphocyte responses. The current importance of research not into bacteria, but into bacterial products, including endotoxins, on the modulation of asthma and allergy is noted. Studies which, along these lines, show an environmental impact on genetic secretion in the phenotype are underlined. Also discussed in passing are several mechanisms which go towards explaining neutrophilic asthma – for many a contradiction, given eosinophilia's stranglehold on asthmatic inflammation.


title: Virological applications of the grid-cell-culture technique

text: Abstract Whole mounts of intact virus-infected cells have been used for several decades to examine virus-cell relationships and virus structure. The general concept of studying virus structure in association with the host cell has recently been expanded to reveal interactions between viruses and the cytoskeleton. The procedure permits utilization of immuno-gold protocols using both the transmission and scanning electron microscopes. The grid-cell-culture technique is reviewed to explain how it can be exploited to provide valuable information about virus structure and replication in both diagnostic and research laboratories. The use of the technique at the research level is discussed using bluetongue virus as a model. The procedure can provide basic structural information about intact virions and additional data on the intracellular location of viruses and virus-specific structures and about the mode of virus release from infected cells. Application of immunoelectron microscopy reveals information on the protein composition of not only released virus particles but also cell surface and cytoskeletal-associated viruses and virus-specific structures. Collectively, this simple and physically gentle technique has provided information which would otherwise be difficult to obtain.


title: Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics

text: OBJECTIVE: Olfactory dysfunction (OD)—hyposmia or anosmia—is a symptom of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to better determine prevalence, severity, and timing of OD in COVID-19 relative to other sinonasal and pulmonary symptoms. STUDY DESIGN: Prospective, cross-sectional. SETTING: Regional/cantonal hospital. SUBJECTS: In total, 103 patients diagnosed with COVID-19 with reverse transcription polymerase chain reaction (RT-PCR)–based testing. METHODS: All patients testing positive for COVID-19 at Kantonsspital Aarau over a 6-week period were approached. Timing and severity (at its worst, on scale of 0 [none], 1 [mild], 2 [moderate], and 3 [severe]) of OD, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath (SOB) were assessed for each patient. RESULTS: Prevalence of OD was 61.2%, and severity of OD was strongly correlated with severity of loss of taste experienced (ρ = 0.87, P < .001). OD was experienced on the first day of COVID-19 by 8.7% and overall occurred at median infection day 3 (mean, 3.4; range, 0-12). Most experiencing OD reported anosmia, and mean severity of all with OD was moderate to severe (mean [SD], 2.7 [0.6]). Nasal obstruction (49.5%) and rhinorrhea (35.0%) were frequently reported but not correlated with OD. SOB was more severe in patients with OD. OD was associated negatively with older age (OR, 0.96; 95% CI, 0.93-0.99; P = .007) and positively with female sex (OR, 2.46; 95% CI, 0.98-6.19; P = .056). CONCLUSIONS: OD is highly prevalent during COVID-19, occurring early and severely, often in conjunction with loss of taste. OD is associated negatively with older age and positively with female sex. Patients with OD may also experience more severe SOB.


title: Home Dialysis in the COVID-19 Era

text: Abstract The Coronavirus Disease 19 (COVID-19) pandemic has had a significant impact on End Stage Kidney Disease (ESKD) patients and their care, especially given the potential for severe COVID-19 disease in those with a depressed immune status. Patients receiving in-center hemodialysis have been particularly affected by this pandemic due to their need to travel multiple times a week to receive treatment. Although patients on home dialysis are able to avoid such exposure, they face their own unique challenges. In this review, we will discuss the challenges posed by the COVID-19 pandemic for patients on home dialysis, the impact of COVID-19 on various aspects of their care, and the resultant rapid adaptations in policy/health care delivery mechanisms with implications for the future care of home dialysis patients.


title: Antigenic structure of the hemagglutinin of H9N2 influenza viruses

text: The hemagglutinins (HAs) of H9 influenza viruses isolated from birds and mammals of different species were antigenically and genetically analyzed. Antigenic variants were selected from A/swine/Hong Kong/10/98 (H9N2) and A/duck/Hokkaido/13/00 (H9N2) in the presence of monoclonal antibodies (MAbs). Based on the reactivity patterns of these mutants with a panel of MAbs, at least five non-overlapping antigenic sites were defined using eight MAbs which recognized seven distinct epitopes on the H9 HA molecule. Based on the reactivity patterns with the panel of monoclonal antibodies, 21 H9N2 virus strains isolated from birds and mammals were divided into 7 antigenically distinct groups. The present findings indicate that it is important to monitor the antigenic variation in H9 influenza viruses. The panel of MAbs in the present study, thus, should be useful for detailed antigenic analysis of the H9 HAs for epidemiological studies, the selection of vaccine strains, and diagnosis.


title: Review of trials currently testing treatment and prevention of COVID-19

text: BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken all over the world. OBJECTIVES: We summarised all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS: and interventions: No restrictions in terms of participants’ age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term “coronavirus” or “COVID-19” from their inception until 26(th) March 2020.Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSION: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.


title: Requirements for schwann cell migration within cns environments: A viewpoint

text: Abstract Schwann cells are able to migrate into the CNS and myelinate CNS axons in a number of developmental and pathological situations. Morphological studies based on normal, mutant and experimentally-lesioned tissue have indicated that Schwann cells are only able to enter the CNS when the integrity of the astrocytic glia limitans is disrupted. The significance and subtlety of the interactions between Schwann cells and astrocytes have been further explored by glial cell transplantation studies. These studies support in vitro observations on Schwann cell behaviour in highlighting the importance of extracellular matrix for both migration and myelin sheath formation. The failure of Schwann cells to intermix with astrocytes is an important aspect of glial cell biology which will have a bearing on efforts to remyelinate demyelinated axons by Schwann cell-transplantation.


title: Molecular epidemiology of human adenovirus infections in Denmark, 2011–2016

text: Abstract Background Human adenoviruses (HAdVs) can cause respiratory tract infections, conjunctivitis, diarrhoea and outbreaks have been reported. However, little is known about the disease burden and the molecular epidemiology of HAdV. Objectives To retrospectively perform a molecular characterization of HAdV positive samples received at Statens Serum Institut during the period 2011–2016 and to compare this with demographic information, geographic location, sample collection date and type and co-infection with other viral pathogens. Study design 152 HAdV positive samples were genotyped by Sanger sequencing of a fragment of the hexon gene using published primers along with a newly developed primer set for enhanced genotyping of HAdV D. Phylogenetic analysis was used for genotyping and genotypes were compared with epidemiological information. In addition, HAdV burden and co-infection was evaluated for samples tested in laboratory analysis packages. Results Six out of seven HAdV species were identified and represented by 13 types. Young children (<5 years old) were more likely to be positive for HAdV and co-infections with other gastrointestinal or respiratory viruses were common. Possible outbreaks of ocular infections due to HAdV D could not be confirmed. Conclusion A diverse set of HAdV species were circulating in Denmark in the study period and although possible transmission clusters were identified, this could not be verified with current genotyping methods Young children were commonly affected by HAdV infection and co-infections with other viral pathogens were frequent suggesting a possible underestimation of the real HAdV burden.


title: A case of COVID-19 and pneumonia returning from Macau in Taiwan: Clinical course and anti-SARS-CoV-2 IgG dynamic

text: A 46-year-old woman presented to the emergency department with 2-day fever and cough at seven days after returning from Macau. COVID-19 and pneumonia was diagnosed based on the positive real-time RT-PCR tests for oropharyngeal swab samples and the presence of anti-SARS-COV-2 IgG starting from the illness day 11 and post-exposure 18–21 days.


title: Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production

text: The arterivirus family (order Nidovirales) of single-stranded, positive-sense RNA viruses includes porcine respiratory and reproductive syndrome virus and equine arteritis virus (EAV). Their replicative enzymes are translated from their genomic RNA, while their seven structural proteins are encoded by a set of small, partially overlapping genes in the genomic 3′-proximal region. The latter are expressed via synthesis of a set of subgenomic mRNAs that, in general, are functionally monocistronic (except for a bicistronic mRNA encoding the E and GP2 proteins). ORF5, which encodes the major glycoprotein GP5, has been used extensively for phylogenetic analyses. However, an in-depth computational analysis now reveals the arterivirus-wide conservation of an additional AUG-initiated ORF, here termed ORF5a, that overlaps the 5′ end of ORF5. The pattern of substitutions across sequence alignments indicated that ORF5a is subject to functional constraints at the amino acid level, while an analysis of substitutions at synonymous sites in ORF5 revealed a greatly reduced frequency of substitution in the portion of ORF5 that is overlapped by ORF5a. The 43–64 aa ORF5a protein and GP5 are probably expressed from the same subgenomic mRNA, via a translation initiation mechanism involving leaky ribosomal scanning. Inactivation of ORF5a expression by reverse genetics yielded a severely crippled EAV mutant, which displayed lower titres and a tiny plaque phenotype. These defects, which could be partially complemented in ORF5a-expressing cells, indicate that the novel protein, which may be the eighth structural protein of arteriviruses, is expressed and important for arterivirus infection.


title: Production of IL-8, IL-17, IFN-gamma and IP-10 in human astrocytes correlates with alphavirus attenuation

text: Abstract Venezuelan equine encephalitis virus (VEEV) is an important, naturally emerging zoonotic pathogen. Recent outbreaks in Venezuela and Colombia in 1995 indicate that VEEV still poses a serious public health threat. Astrocytes may be target cells in human and mouse infection and they play an important role in repair through gliosis. In this study, we report that virulent VEEV efficiently infects cultured normal human astrocytes, three different murine astrocyte cell lines and astrocytes in the mouse brain. The attenuation of virus replication positively correlates with the increased levels of production of IL-8, IL-17, IFN-gamma and IP-10. In addition, VEEV infection induces release of basic fibroblast growth factor and production of potent chemokines such as RANTES and MIP-1-beta from cultured human astrocytes. This growth factor and cytokine profile modeled by astrocytes in vitro may contribute to both neuroprotection and repair and may play a role in leukocyte recruitment in vivo.


title: Exhaled air dispersion during bag-mask ventilation and sputum suctioning - Implications for infection control

text: Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.


title: Validation of a fecal scoring scale in puppies during the weaning period

text: Abstract In puppies weaning is a high risk period. Fecal changes are frequent and can be signs of infection by digestive pathogens (bacteria, viruses, parasites) and indicators of nutritional and environmental stress. The aim of this study was to define a pathological fecal score for weaning puppies, and to study the impact on that score of two intestinal viruses (canine parvovirus type 2 and canine coronavirus). For this, the quality of stools was evaluated on 154 puppies between 4 and 8weeks of age (100 from small breeds and 54 from large breeds). The scoring was performed immediately after a spontaneous defecation based on a 13-point scale (from 1; liquid to 13; dry and hard feces). Fecal samples were frozen for further viral analysis. Each puppy was weighed once a week during the study period. The fecal score regarded as pathological was the highest score associated with a significant reduction in average daily gain (ADG). Fecal samples were checked by semi-quantitative PCR or RT-PCR for canine parvovirus type 2 and canine coronavirus identification, respectively. The quality of feces was affected by both age and breed size. In small breeds, the ADG was significantly reduced under a fecal score of 6 and 7 for puppies at 4–5 and 6–8weeks of age, respectively. In large breeds, the ADG was significantly reduced under a fecal score of 5 whatever the age of the puppy. Whereas a high viral load of canine parvovirus type 2 significantly impacted feces quality, no effect was recorded for canine coronavirus. This study provides an objective threshold for evaluation of fecal quality in weaning puppies. It also emphasizes the importance to be given to age and breed size in that evaluation.


title: Blood Transfusion Services

text: Blood transfusion services are an important part of the health-care system since blood transfusion is required in a number of frequently occurring clinical situations: Major surgical procedures, including treatment of trauma patients; obstetric care with major bleeding during child birth; and treatment of several medical diseases, especially hematological diseases. This article outlines the essential safety aspects of blood transfusion from the proper selection of the unpaid blood donor to processing and appropriate testing of the blood unit to safety aspects of transfusion, which include the appropriate clinical use of blood and blood components. The importance of accurate reporting of any adverse reactions to blood transfusion, which form the basis for a hemovigilance system, is reviewed.


title: The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase

text: Abstract The 5′-most gene, gene 1, of the genome of murine coronavirus, mouse hepatitis virus (MHV), is presumed to encode the viral RNA-dependent RNA polymerase. We have determined the complete sequence of this gene of the JHM strain by cDNA cloning and sequencing. The total length of this gene is 21,798 nucleotides long, which includes two overlapping, large open reading frames. The first open reading frame, ORF 1 a, is 4488 amino acids long. The second open reading frame, ORF 1 b, overlaps ORF 1 a for 75 nucleotides, and is 2731 amino acids long. The overlapping region may fold into a pseudoknot RNA structure, similar to the corresponding region of the RNA of avian coronavirus, infectious bronchitis virus (IBV). The in vitro transcription and translation studies of this region indicated that these two ORFs were most likely translated into one polyprotein by a ribosomal frameshifting mechanism. Thus, the predicted molecular weight of the gene 1 product is more than 800,000 Da. The sequence of ORF 1 b is very similar to the corresponding ORF of IBV. In contrast, the ORF 1 a of these two viruses differ in size and have a high degree of divergence. The amino acid sequence analysis suggested that ORF 1 a contains several functional domains, including two hydrophobic, membrane-anchoring domains, and three cysteine-rich domains. It also contains a picornaviral 3C-like protease domain and two papain-like protease domains. The presence of these protease domains suggests that the polyprotein is most likely processed into multiple protein products. In contrast, the ORF 1b contains polymerase, helicase, and zinc-finger motifs. These sequence studies suggested that the MHV gene 1 product is involved in RNA synthesis, and that this product is processed autoproteolytically after translation. This study completes the sequence of the MHV genome, which is 31 kb long, and constitutes the largest viral RNA known.


Caring for Pediatric Patients with Diabetes amidst the COVID-19 Storm


title: Trimethylaurintricarboxylic acid inhibits human DNA methyltransferase 1: insights from enzymatic and molecular modeling studies

text: DNA methyltransferase 1 (DNMT1) is an emerging target for the treatment of cancer, brain disorders, and other diseases. Currently, there are only a few DNMT1 inhibitors with potential application as therapeutic agents or research tools. 5,5-Methylenedisalicylic acid is a novel scaffold previously identified by virtual screening with detectable although weak inhibitory activity of DNMT1 in biochemical assays. Herein, we report enzyme inhibition of a structurally related compound, trimethylaurintricarboxylic acid (NSC97317) that showed a low micromolar inhibition of DNMT1 (IC(50) = 4.79 μM). Docking studies of the new inhibitor with the catalytic domain of DNMT1 suggest that NSC97317 can bind into the catalytic site. Interactions with amino acid residues that participate in the mechanism of DNA methylation contribute to the binding recognition. In addition, NSC97317 had a good match with a structure-based pharmacophore model recently developed for inhibitors of DNMT1. Trimethylaurintricarboxylic acid can be a valuable biochemical tool to study DNMT1 inhibition in cancer and other diseases related to DNA methylation. [Figure: see text]


title: Pediatric Ear, Nose, and Throat Emergencies

text: Acute otitis media is the most common infection for which antibiotics are prescribed in children, resulting in more than 20 million antibiotic prescriptions annually. New practice guidelines published by the American Academy of Pediatrics and the American Academy of Family Physicians call for the judicious use of antibiotics in view of increasing antibiotic resistance and the unclear necessity of the use of antibiotics in children with uncomplicated acute otitis media. This article reviews those guidelines, several other common ear, nose, and throat entities, including sinusitis and dental emergencies, and current strategies in diagnosis and treatment.


title: SARS-CoV-2 infection and glucose homeostasis in pregnancy. What about antenatal corticosteroids?

text: Abstract Background and aims Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. Methods We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. Results SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. Conclusions Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.


title: Infection control in dental health care during and after the SARS‐CoV‐2 outbreak

text: COVID‐19 is an emerging infectious disease caused by the widespread transmission of the coronavirus SARS‐CoV‐2. Some of those infected become seriously ill. Others do not show any symptoms, but can still contribute to transmission of the virus. SARS‐CoV‐2 is excreted in the oral cavity and can be spread via aerosols. Aerosol generating procedures in dental health care can increase the risk of transmission of the virus. Due to the risk of infection of both dental healthcare workers and patients, additional infection control measures for all patients are strongly recommended when providing dental health care. Consideration should be given to which infection control measures are necessary when providing care in both the current situation and in the future.


title: Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial

text: BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289


title: How the COVID‐19 pandemic may impact public support for clinical xenotransplantation in the United States?

text: Many patients who would undergo organ transplantation cannot proceed due to the inability of human organ donation to satisfy medical needs. Xenotransplantation has the potential to offer unlimited availability of pig organs for transplantation, and pig‐to‐non‐human primate models have demonstrated outcomes that may soon justify clinical trials. However, one of the unique ethical challenges faced by xenotransplantation is that the risk of introducing potential zoonotic disease into the community must be weighed along with the benefit to the patient. While most experts believe that zoonosis is manageable, apprehension over disease transmission from animal donors to human recipients remains a frequent concern of many who are undecided or opposed to clinical xenotransplantation. The COVID‐19 pandemic represents a scenario (rapid worldwide spread of a highly contagious novel zoonotic disease with no natural defense in humans) that would seem to justify apprehension, especially in the United States, which has largely avoided previous pandemic outbreaks. However, there are many differences between zoonosis found in the wild or after xenotransplantation that favor the safety of the latter. Still, these differences, as well as the benefits of xenotransplantation, are not widely understood outside of the field. We must therefore ask what impact the COVID‐19 pandemic will have on attitudes toward xenotransplantation.


title: Current Safety Sterilization and Tissue Banking Issues for Soft Tissue Allografts

text: Allografts used in orthopedic surgery have steadily increased. With concerns regarding tissue safety and processing, governing entities have increased their regulation. This review articles discusses current testing and processing of allografts as well as the rules of their handling.


title: Effect of Interactions Between Lower Airway Bacterial and Rhinoviral Infection in Exacerbations of COPD

text: Study objectives The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. Design Prospective cohort study. Setting Outpatient Department, London Chest Hospital, London, UK. Patients Thirty-nine patients with COPD. Measurements We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. Results A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. Conclusions The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.


docid: yemyanvv

title: Immune surveillance in the skin: mechanisms and clinical consequences

text: The skin, as the primary interface between the body and the environment, provides the first line of defence against a broad array of microbial pathogens and trauma. In addition to its properties as a physical barrier, the skin has many active defence mechanisms. In this review, we discuss the interaction between the innate and adaptive immune systems in the skin as a model for immune function at epithelial-cell interfaces with the environment. How these mechanisms account for the robust nature of cutaneous immune surveillance and how their dysregulation drives the pathogenesis of inflammatory skin disorders and skin-based tumours are the subjects of this review.


title: Crimean-Congo hemorrhagic fever in children

text: Abstract Background Crimean-Congo hemorrhagic fever (CCHF) virus causes a severe disease in humans with a mortality up to 30%. In Turkey there has been an increase in the number of cases during years since 2002. Humans of all ages living in endemic areas,especially those who are working as shepherds and toddlers, have high risk of acquiring CCHF. Objectives The epidemiological, clinical, and laboratory characteristics of the children, who were diagnosed as Crimean-Congo hemorrhagic fever (CCHF) were described. Study design The children infected with CCHF virus between April 2008 and October 2009, and hospitalised in Ankara Dışkapı Children's and Research Hospital were included. Results Laboratory diagnosis was set by detection of CCHF IgM antibodies and/or genetic detection of CCHF virus. Thirtyone cases included to the study, and all were from the northeastern Anatolia and the southern parts of Black sea region. The mean age was 9.45±4.9 years, the proportion of females was 38.7%. The majority (87%) of the cases had the history of tick bite. There was no fatal case. All the patients had the history of fever. Malaise,tonsillopharyngitis, nausea-vomiting, headache, diarrhea, myalgia and rash were the most common symptoms. The mean AST and ALT levels on the admission were 116 (range 25–389) and 61 (range 8–180)U/L respectively. The mean platelet count on admission was 125,000/mm3, and the lowest was 23,000/mm3. The mean of the lowest white blood cell count was 2353/mm3 and the mean of the highest lactate dehydrogenase was 861IU/L. Conclusions The clinical course of CCHF among children seems to be milder than in adults. Tonsillopharyngitis is a common symptom among children with CCHF.


title: Plant‐made vaccines for humans and animals

text: The concept of using plants to produce high‐value pharmaceuticals such as vaccines is 20 years old this year and is only now on the brink of realisation as an established technology. The original reliance on transgenic plants has largely given way to transient expression; proofs of concept for human and animal vaccines and of efficacy for animal vaccines have been established; several plant‐produced vaccines have been through Phase I clinical trials in humans and more are scheduled; regulatory requirements are more clear than ever, and more facilities exist for manufacture of clinic‐grade materials. The original concept of cheap edible vaccines has given way to a realisation that formulated products are required, which may well be injectable. The technology has proven its worth as a means of cheap, easily scalable production of materials: it now needs to find its niche in competition with established technologies. The realised achievements in the field as well as promising new developments will be reviewed, such as rapid‐response vaccines for emerging viruses with pandemic potential and bioterror agents.


title: Chapter 10 Advax Adjuvant A Potent and Safe Immunopotentiator Composed of Delta Inulin

text: Abstract Highly potent adjuvants commonly have reactogenicity and safety issues. Unlike other immunologically active polysaccharides, inulin has no immune activity in its native soluble form, but when crystallized into the stable delta inulin isoform, it acquires potent immune actions. Most notably, delta inulin enhances both humoral and cellular immune responses against vaccine antigens, translating into enhanced protection against a broad range of viral, bacterial, parasitic, and toxin-mediated diseases. Delta inulin is distinct compared with typical vaccine adjuvants as it does not require adsorption to antigen and does not appear to work through induction of inflammatory danger signals. Delta inulin manufactured under current Good Manufacturing Practices (referred to as Advax) has been proved to be safe and effective in human trials of influenza vaccines, hepatitis B vaccines, and insect sting allergy vaccines. Advax thereby represents a novel nonreactogenic immune modulator with potential utility across a broad range of human prophylactic and therapeutic vaccines.


title: Membrane topology of gp41 and amyloid precursor protein: Interfering transmembrane interactions as potential targets for HIV and Alzheimer treatment

text: Abstract The amyloid precursor protein (APP), that plays a critical role in the development of senile plaques in Alzheimer disease (AD), and the gp41 envelope protein of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), are single-spanning type-1 transmembrane (TM) glycoproteins with the ability to form homo-oligomers. In this review we describe similarities, both in structural terms and sequence determinants of their TM and juxtamembrane regions. The TM domains are essential not only for anchoring the proteins in membranes but also have functional roles. Both TM segments contain GxxxG motifs that drive TM associations within the lipid bilayer. They also each possess similar sequence motifs, positioned at the membrane interface preceding their TM domains. These domains are known as cholesterol recognition/interaction amino acid consensus (CRAC) motif in gp41 and CRAC-like motif in APP. Moreover, in the cytoplasmic domain of both proteins other α-helical membranotropic regions with functional implications have been identified. Recent drug developments targeting both diseases are reviewed and the potential use of TM interaction modulators as therapeutic targets is discussed.


Melatonina, coronavirus, enfermedad cardiovascular y emergencia geriátrica: ¡usemos todo lo que tenemos! Respuesta


title: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV

text: [Image: see text] SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.


title: Snapshot of the evolution and mutation patterns of SARS-CoV-2

text: The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.


docid: qdwvenen

title: Characterization of enterotoxigenic E. coli (ETEC), Shiga-toxin producing E. coli (STEC) and necrotoxigenic E. coli (NTEC) isolated from diarrhoeic Mediterranean water buffalo calves (Bubalus bubalis)

text: Abstract Two hundred and twenty Escherichia coli isolates from 314 Mediterranean water buffalo calves less than 4weeks old affected by severe diarrhoea with a lethal outcome were characterized for the presence of the virulence factors LT, ST, Stx1, Stx2, haemolysins, intimin, CNF1, CNF2, CDT-I, CDT-II, CDT-III, CDT-IV, and F17-related fimbriae (F17a, F17b, F17c, F17d). The prevalence of ETEC, STEC and NTEC were 1.8%, 6.8% and 20.9%, respectively. The ETEC isolates were all LT-positive and ST-negative. The STEC isolates were all Stx and intimin-positive, with Stx1 (80%) more frequent than Stx2 (27%). The NTEC isolates were all CNF and Hly-positive, with CNF2 (83%) more frequent than CNF1 (22%). Susceptibility assays to 11 antimicrobials displayed high rates of resistance (>30%) to antimicrobials tested. These data show that the most prevalent strains in diarrhoeic water buffalo calves were NTEC, mostly CNF2 and HlyA-positive, with strong associations CNF2/CDT-III and CNF2/F17c.


title: Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment

text: OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.


title: Rat poison and food security in the People’s Republic of China: focus on tetramethylene disulfotetramine (tetramine)

text: The last several years have seen a large number of mass poisonings in mainland China, particularly those caused by illicit rodenticides. One rat poison, tetramine (tetramethylene disulfotetramine) is responsible for a great percentage of death and injury in the People’s Republic of China (PRC). Tetramine is an acutely toxic substance with human oral toxicity estimated as low as 0.1 mg/kg, and is widely available in open markets in mainland China—this despite being prohibited for manufacture or sale in the PRC. Being a GABA antagonist, and having an extremely potent effect on the brain stem, many victims can quickly fall into convulsions and die within hours following ingestion. With no known effective antidote at this time, clinical data from the PRC show that acute cases of tetramine poisoning are extremely difficult to treat. The widespread use of tetramine—including its reported sale at a Malaysian outdoor market in September 2002—could exacerbate its hazard to public health, particularly in those areas having large overseas Chinese populations.


title: Immunity to PRRSV: Double-edged sword

text: Abstract The immune system is a double-edged sword for porcine reproductive and respiratory syndrome virus (PRRSV) infection. On one edge PRRSV has a predilection for immune cells and the disease manifestations can be linked directly to changes in the immune system. PRRSV appears to replicate extensively, if not exclusively, in cells of the immune lineage, notably macrophages; the direct replication of which may lead to immunosuppression, precipitate secondary infection and/or mediate disease. On the other edge, the virus stimulates immunity post-infection that protects an animal from re-infection. A vast array of structural and functionally distinct antibody specific to PRRSV are generated following infection or vaccination. Discrete populations of functional antibodies appear at different times and possibly reflect reactivity to different PRRSV polypeptides. Cell-mediated immune responses specific to PRRSV can be detected in various exposed pigs as well. Thus, the immune system appears to be intimately involved in both the disease process and protection from disease. It is unclear at this state of understanding what immune compartment provides protective immunity. Is it humoral (i.e. antibodies), selective functionally distinct populations of antibodies specific for selected PRRSV polypeptides or is cellular immunity essential for protection, or both. This review will attempt to summarize the current state of knowledge of the complex interaction of the immune system and PRRSV.


title: Alabama university to study emotions, behavior and COVID‐19

text: A psychology researcher at the University of Alabama was awarded a federal grant to study how people's emotions influence their response to the spread of the novel coronavirus. “Right now, there is a tremendous amount of uncertainty in day‐to‐day life around the globe,” Philip Gable, Ph.D., associate professor of psychology, said in a March 30 university news release. “We are interested in the role uncertainty plays in how people feel and behave, and we are especially interested to see how non‐conscious emotions toward avoiding the virus influence health behaviors.” Gable is leading the project awarded nearly $65,000 under the National Science Foundation's (NSF's) Rapid Response Research funding program, which is set up to review and fund projects with an urgent need to gather data during or right after emergency events and natural disasters. The research at UA is part of the NSF's effort to quickly start nonmedical, nonclinical care research that can be used immediately to explore how to model and understand the spread of COVID‐19, to inform and educate about the science of virus transmission and prevention and to encourage the development of processes and actions to address this global challenge. The spreading COVID‐19 in the United States creates a social psychological problem of a scale never encountered in modern times, the release stated. The findings will be published and the anonymous data from the app will be publicly available.


title: Telehealth in Uro-oncology Beyond the Pandemic: Toll or Lifesaver?

text: BACKGROUND: Telehealth services are rapidly embraced in uro-oncology due to the current coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To determine patients’ perspective on adoption of telehealth as a response to the pandemic and its sustainability in the future. DESIGN, SETTING, AND PARTICIPANTS: Following a COVID-19 outbreak, 101 patients with advanced genitourinary cancers are currently managed “virtually” for therapy administration at our tertiary care unit. They were surveyed about the current situation, and current and long-term employment of telehealth. INTERVENTION: Rapid implementation of virtual patient management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients’ perception of anxiety of COVID-19 and cancer, perspective on telehealth measures as a reaction to the current COVID-19 pandemic, and long-term acceptance were used as outcomes. Wilcoxon matched-pair signed rank test, chi-square test, and Mann-Whitney U test were performed. RESULTS AND LIMITATIONS: Of 101 patients, 92 answered the questionnaire, with 71 (77.2%) responding virtually by e-mail or phone call. Anxiety of cancer (6/10, interquartile range [IQR] 3–8) superseded that of COVID-19 (four/10, IQR 2–5.25, p < 0.001), and patients oppose temporary treatment interruption. Of the patients, 66.0% perceive their susceptibility to COVID-19 as equal to or lower than the general population and 52.2% believe that COVID-19 will not affect their therapy. In future, patients (62.6%) prefer to maintain in-person appointments as opposed to complete remote care, but accept remote care during the pandemic (eight/10, IQR 5–9). Beyond the crisis, maintaining telehealth has low preference rates (four/10, IQR 2–7), with high acceptance for external laboratory controls (60.9%) and online visit management (48.9%), but lower acceptance for remote treatment planning including staging discussions (44.6%) and for referral to secondary care oncologists (17.4%). CONCLUSIONS: Despite the pandemic, cancer remains the key concern and patients are not willing to compromise on their treatment. Rapid implementation of telehealth is tolerated well during the need of social distancing, with a clear “red line” concerning changes in existing patient-physician relationships. Balancing future implementation of telehealth while considering patients’ demand for personal relationships will ensure human dignity in uro-oncology. PATIENT SUMMARY: We queried patients with genitourinary cancers treated in an almost virtual setting following a local coronavirus outbreak. Acceptance of telehealth during the current situation is high; however, long-term implementation of the adapted services is less favored. We deduce that patient-physician relationship is crucial for cancer patients and needs to be balanced against measures for social distancing to forge the future management.


title: Viral–bacterial co-infections in the respiratory tract

text: Preceding or concurrent viral respiratory tract infection can predispose to secondary bacterial co-infection throughout the airway. The mechanisms by which viruses promote these superinfections are diverse and replete. Whereas we understand much as to how viruses damage the airway and dysregulate both innate and acquired immune responses which, in turn, supports bacterial growth, adherence and invasion into normally sterile sites within the respiratory tract, new information regarding these co-infections is being gained from recent advances in microbiome research and our enhanced appreciation of the contribution of bacterial biofilms, among others. The advanced understanding obtained by continued research efforts in all aspects of viral–bacterial co-infections of the respiratory tract will allow us to devise novel approaches for disease prevention as well as to develop more effective therapeutics.


title: Implementing fit testing for N95 filtering facepiece respirators: Practical information from a large cohort of hospital workers

text: Qualitative fit testing for N95 respirators was conducted on 1271 health care workers. All male participants were fitted with a respirator. Six females, all under age 40 years, were not successfully fitted. The first-choice respirator provided a successful fit in 95.1% of the men and 85.4% of the women. Gender and age in women were significant factors associated with successful fitting. These differences should be considered when implementing a respiratory protection program.


title: Isolation and characterization of porcine epidemic diarrhea virus associated with the 2014 disease outbreak in Mexico: case report

text: BACKGROUND: Interest in porcine epidemic diarrhea has grown since the 2013 outbreak in the United States caused major losses, with mortality rates up to 100 % in suckling piglets. In Mexico, an outbreak of porcine epidemic diarrhea, characterized by 100 % mortality in piglets, began in March 2014 in the State of Mexico. METHODS: The aim of this study was to confirm and identify porcine epidemic diarrhea virus (PEDV) in samples from piglets with suggestive clinical signs using virological, histological, and molecular techniques. Necropsy was performed on 13 piglets from two litters with initial and advanced clinical signs. Suggestive lesions of acute infection with PEDV were detected in histological sections of the small and large bowels; specifically, multiple virus particles with visible crown-shaped projections were observed using electron microscopy and negative staining. Viral isolation was performed in Vero cells with trypsin. Infection was monitored by observation of cytopathic effect, and titration was determined by TCID(50)/ml. The presence of the PEDV in cultures and clinical samples was confirmed by RT-PCR amplification and sequencing of a 651-bp segment of the S glycoprotein gene, as well as a 681-bp matrix protein gene. RESULTS: The nucleotide sequence analysis of the Mexican isolates showed marked homology to viruses that circulated in 2013 in Colorado, USA. CONCLUSIONS: In this paper we confirm the isolation and characterization of PEDV from animals with early and advanced clinical signs.


title: Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate 70

text: BACKGROUND: Hepatitis B virus (HBV) infection is a major health concern with more than two billion individuals currently infected worldwide. Because of the limited effectiveness of existing vaccines and drugs, development of novel antiviral strategies is urgently needed. Heat stress cognate 70 (Hsc70) is an ATP-binding protein of the heat stress protein 70 family. Hsc70 has been found to be required for HBV DNA replication. Here we report, for the first time, that combined siRNAs targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV expression and replication. METHODS: We constructed two plasmids (S1 and S2) expressing short hairpin RNAs (shRNAs) targeting surface open reading frame of HBV(HBVS) and one plasmid expressing shRNA targeting Hsc70 (siHsc70), and we used the EGFP-specific siRNA plasmid (siEGFP) as we had previously described. First, we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green fluorescent protein (EGFP) reporter system and flow cytometry in HEK293 and T98G cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV) in combination with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF-α induction were measured by quantitative real-time PCR and ELISA. RESULTS: Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%–90% reduction in EGFP signal relative to the control. This combinational RNAi effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting in up to a 3.36 log(10) reduction in HBV load in the HepG2.2.15 cell culture supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used separately, and this approach can enhance potency in suppressing ongoing viral gene expression and replication in HepG2.2.15 cells while forestalling escape by mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70 produced no cytotoxicity and induced no production of IFN-α, IFN-β and TNF-α in transfected cells. CONCLUSIONS: Our combinational RNAi was sequence-specific, effective against wild-type and mutant drug-resistant HBV strains, without triggering interferon response or producing any side effects. These findings indicate that combinational RNAi has tremendous promise for developing innovative therapy against viral infection.


title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine

text: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4(+) and CD8(+) T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.


title: Full-length genome analysis of two genetically distinct variants of porcine epidemic diarrhea virus in Thailand

text: Abstract Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007 and a pandemic variant containing an insertion and deletion in the spike gene was responsible for outbreaks. In 2014, there were further outbreaks of the disease occurring within four months of each other. In this study, the full-length genome sequences of two genetically distinct PEDV isolates from the outbreaks were characterized. The two PEDV isolates, CBR1/2014 and EAS1/2014, were 28,039 and 28,033 nucleotides in length and showed 96.2% and 93.6% similarities at nucleotide and amino acid levels respectively. In total, we have observed 1048 nucleotide substitutions throughout the genome. Compared to EAS1/2014, CBR1/2014 has 2 insertions of 4 (56GENQ59) and 1 (140N) amino acid positions 56–59 and 140, and 2 deletions of 2 (160DG161) and 1 (1199Y) amino acid positions 160–161 and 1199. The phylogenetic analysis based on full-length genome of CBR1/2014 isolate has grouped the virus with the pandemic variants. In contrast, EAS1/2014 isolate was grouped with CV777, LZC and SM98, a classical variant. Our findings demonstrated the emergence of EAS1/2014, a classical variant which is novel to Thailand and genetically distinct from the currently circulating endemic variants. This study warrants further investigations into molecular epidemiology and genetic evolution of the PEDV in Thailand.


10 Adenovirus Vaccines


Treating hypoxemic COVID-19 “ARDS” patients with almitrine: The earlier the better?


docid: duxyohen

title: Zinc: a new risk factor for pneumonia in the elderly?

text: Zinc may be a new risk factor for pneumonia in the elderly. In this special article, we reviewed the magnitude of the problem of pneumonia (its prevalence, morbidity and mortality) in the elderly, its etiology, and the dysregulation of the immune system associated with increasing age. In addition, we presented evidence from the literature, including work we did recently, that low zinc status (commonly reported in the elderly) impairs immune function, decreases resistance to pathogens, and is associated not only with increased incidence and duration of pneumonia, increased use and duration of antimicrobial treatment, but also with increased overall mortality in the elderly. Inadequate stores of zinc might therefore be a risk factor for pneumonia in the elderly. Randomized, double blind, controlled studies are needed to determine the efficacy of zinc supplementation as a potential low cost intervention to reduce morbidity and mortality due to pneumonia in this vulnerable population.


title: Timeliness of infectious disease reporting, the Netherlands, 2003 to 2017: law change reduced reporting delay, disease identification delay is next

text: BACKGROUND: Timely notification of infectious diseases is essential for effective disease control and needs regular evaluation. AIM: Our objective was to evaluate the effects that statutory adjustments in the Netherlands in 2008 and raising awareness during outbreaks had on notification timeliness. METHODS: In a retrospective analyses of routine surveillance data obtained between July 2003 and November 2017, delays between disease onset and laboratory confirmation (disease identification delay), between laboratory confirmation and notification to Municipal Health Services (notification delay) and between notification and reporting to the National Institute for Public Health and the Environment (reporting delay) were analysed for 28 notifiable diseases. Delays before (period 1) and after the law change (periods 2 and 3) were compared with legal timeframes. We studied the effect of outbreak awareness in 10 outbreaks and the effect of specific guidance messages on disease identification delay for two diseases. RESULTS: We included 144,066 notifications. Average notification delay decreased from 1.4 to 0.4 days across the three periods (six diseases; p < 0.05), reporting delay decreased mainly in period 2 (from 0.5 to 0.1 days, six diseases; p < 0.05). In 2016–2017, legal timeframes were met overall. Awareness resulted in decreased disease identification delay for three diseases: measles and rubella (outbreaks) and psittacosis (specific guidance messages). CONCLUSIONS: Legal adjustments decreased notification and reporting delays, increased awareness reduced identification delays. As disease identification delay dominates the notification chain, insight in patient, doctor and laboratory delay is necessary to further improve timeliness and monitor the impact of control measures during outbreaks.


title: Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus

text: Abstract A total of 281 clinical specimens (nasal swabs and nasopharyngeal aspirates) were tested with the Xpert® Flu/RSV XC. The results were compared to those obtained with the real-time retro transcriptase-polymerase chain reaction assays routinely used in our laboratory. The Xpert® Flu/RSV XC showed sensitivity/specificity of 97.8%/100% and 97.9%/100% for flu and respiratory syncytial virus, respectively.


title: An investigation of district spatial variations of childhood diarrhoea and fever morbidity in Malawi

text: Although diarrhoea and malaria are among the leading causes of child mortality and morbidity in Sub-Saharan Africa, few detailed studies have examined the patterns and determinants of these ailments in the most affected communities. In this paper, we investigate the spatial distribution of observed diarrhoea and fever prevalence in Malawi using individual data for 10,185 children from the 2000 Malawi Demographic and Health survey. We highlight inequalities in child health by mapping the residual district spatial effects using a geo-additive probit model that simultaneously controls for spatial dependence in the data and potential nonlinear effects of covariates. The residual spatial effects were modelled via a Bayesian approach. For both ailments, we were able to identify a distinct district pattern of childhood morbidity. In particular, the results suggest that children living in the capital city are less affected by fever, although this is not true for diarrhoea, where some urban agglomerations are associated with a higher childhood morbidity risk. The spatial patterns emphasize the role of remoteness as well as climatic, environmental, and geographic factors on morbidity. The fixed effects show that for diarrhoea, the risk of child morbidity appears to be lower among infants who are exclusively breastfed than among those who are mixed-fed. However, exclusive breastfeeding was not found to have a protective effect on fever. An important socio-economic factor for both diarrhoea and fever morbidity was parental education, especially maternal educational attainment. Diarrhoea and fever were both observed to show an interesting association with child's age. We were able to discern the continuous worsening of the child morbidity up to 8–12 months of age. This deterioration set in right after birth and continues, more or less linearly until 8–12 months, before beginning to decline thereafter. Independent of other factors, a separate spatial process produces district inequalities in child's health.


title: An Observational Cohort Study of Hydroxychloroquine and Azithromycin for COVID-19: (Can’t Get No) Satisfaction

text: It can be said that SARS-CoV-2 caught the world by surprise. In large part due to globalization, the virus quickly evolved from a serious regional concern to a worldwide pandemic, the likes of which are unprecedented in the last century. In a matter of weeks, COVID-19 became a leading cause of death, with a potential staggering death toll in 2020. Due to a heavy burden of illness, and in the absence of proven therapies, several experimental treatments have been and continue to be prescribed outside of clinical trial settings. Of the potential therapeutic options that showed early promise, few have generated as much controversy, or been subject to such politicization, as hydroxychloroquine. In this issue of the International Journal of Infectious Diseases, Arshad et. al have added more fuel to the fire.


title: Comparison of two broadly multiplexed PCR systems for viral detection in clinical respiratory tract specimens from immunocompromised children

text: Abstract Background The detection of viral respiratory tract infections has evolved greatly with the development of PCR based commercial systems capable of simultaneously detecting a wide variety of pathogens. Objectives Evaluate the relative performance of two commercial broad range systems for the detection of viral agents in clinical respiratory tract specimens from immunocompromised children. Study design A total of 176 patient samples were included in the analysis, representing only the first sample collected for each patient, and excluding failed reactions. Samples were de-identified and assayed in parallel using two different, broadly multiplexed PCR systems: ResPlex™ II Panel v2.0 (ResPlex), Qiagen, Hilden, Germany and FilmArray® Respiratory Panel (FilmArray), Idaho Technology Inc., Salt Lake City, UT. Method comparison was based upon pair-wise concordance of results according to patient age, viral target and number of targets detected. Results The two systems showed an overall concordance, by patient, of 83.8% (p =0.0001). FilmArray detected at least one target in 68.8% of samples, while ResPlex detected at least one target in 56.8%. ResPlex failed to detect 20.7% of FilmArray positives, and FilmArray failed to detect 4% of ResPlex positives. The relative performance of each system (including which system detected a higher number of positive samples) varied when stratified by target viral pathogen. Conclusions Broadly multiplexed PCR is an effective means of detecting large numbers of clinically relevant respiratory viral pathogens.


title: Prevalence of Cryptosporidium parvum in dairy calves and GP60 subtyping of diarrheic calves in central Argentina

text: Cryptosporidiosis of calves is caused by the enteroprotozoan Cryptosporidium spp. The disease results in intense diarrhea of calves associated with substantial economic losses in dairy farming worldwide. The aim of this study was to determine calf, herd, and within-herd Cryptosporidium prevalence and identify Cryptosporidium species and subtypes in calves with diarrhea in intensive dairy herds in central Argentina. A total of 1073 fecal samples were collected from 54 randomly selected dairy herds. Cryptosporidium-oocysts were isolated and concentrated from fecal samples using formol-ether and detected by light microscopy with the modified Ziehl-Neelsen technique. Overall prevalence of oocyst-excreting calves was found to be 25.5% (274/1073) (95% C.I. 22.9; 28.1%). Of the herds studied, 89% (48/54) included at least one infected calf, whereas within-herd prevalence ranged from the absence of infection to 57% (20/35). A highly significant association was found between the presence of diarrhea and C. parvum infection (χ(2) = 55.89, p < 0.001). For species determination, genomic DNA isolated from oocyst-positive fecal samples was subjected to PCR-RFLP of the 18S rRNA gene resulting exclusively in Cryptosporidium parvum identification. C. parvum isolates of calves displaying diarrhea and high rate of excretion of oocysts were subtyped by PCR amplification and direct sequencing of the 60 kDa glycoprotein (GP60) gene. Altogether five GP60 subtypes, designated IIaA18G1R1, IIaA20G1R1, IIaA21G1R1, IIaA22G1R1, and IIaA24G1R1 were identified. Interestingly, IIaA18G1R1 and IIaA20G1R1 were predominant in calves with diarrhea and high infection intensity. Notably, IIaA24G1R1 represents a novel, previously unrecognized C. parvum subtype. The subtype IIaA18G1R1, frequently found in this study, is strongly implicated in zoonotic transmission. These results suggest that calves might be an important source for human cryptosporidiosis in Argentina. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-019-06366-y) contains supplementary material, which is available to authorized users.