title: Ventricular tachycardia storm management in a COVID-19 patient: a case report

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with myocardial involvement. Among cardiovascular manifestations, cardiac arrhythmias seem to be fairly common, although no specifics are reported in the literature. An increased risk of malignant ventricular arrhythmias and electrical storm (ES) has to be considered. CASE SUMMARY: We describe a 68-year-old patient with a previous history of coronary artery disease and severe left ventricular systolic disfunction, who presented to our emergency department describing cough, dizziness, fever, and shortness of breath. She was diagnosed with COVID-19 pneumonia, confirmed after three nasopharyngeal swabs. Ventricular tachycardia (VT) storm with multiple implantable cardioverter defibrillator (ICD) shocks was the presenting manifestation of cardiac involvement during the COVID-19 clinical course. A substrate-based VT catheter ablation procedure was successfully accomplished using a remote navigation system. The patient recovered from COVID-19 and did not experience further ICD interventions. DISCUSSION: To date, COVID-19 pneumonia associated with a VT storm as the main manifestation of cardiac involvement has never been reported. This case highlights the role of COVID-19 in precipitating ventricular arrhythmias in patients with ischaemic cardiomyopathy who were previously stable.


Zika as still another argument for a new path to vaccine development


title: Viral Control of Mitochondrial Apoptosis

text: Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.


title: Role, function and challenges of multidisciplinary centres for rare diseases exemplified for neurofibromatosis type 1 syndrome

text: PURPOSE: Neurofibromatosis type 1 (NF1) syndrome is a common rare/orphan disease that manifests itself early in the paediatric age. It imposes a considerable burden upon patients as well as on caregivers. Decisions regarding optimal care often rely on several medical instances working together as a team. METHODS: The authors reviewed the literature and supplied a description of their own clinical work at the NF1 centres. RESULTS: The experience of a multidisciplinary teamwork of three NF centres was summarized in order to enhance awareness for possible multidisciplinary ways of delivery of health and health-related aspects of care to NF1 patients. Both population-focused research centres and family-focused centres were reviewed. CONCLUSIONS: Chronic rare diseases that start in the paediatric age mandate long-term follow-up most often by several disciplines. NF1 syndrome is an example of a multidisciplinary centre in order to enhance the quality of care.


docid: ybocrpyt

title: Induction of innate immune response following infectious bronchitis corona virus infection in the respiratory tract of chickens

text: Abstract Infectious bronchitis virus (IBV) replicates in the epithelial cells of trachea and lungs of chicken, however the mechanism of generation of innate immune response against IBV infection in these tissues has not been fully characterized. Our objective was to study innate responses induced early following IBV infection in chickens. Initiation of the transcription of selected innate immune genes such as TLR3, TLR7, MyD88, IL-1β and IFN-β, as well as recruitment of macrophages, were evident following an initial down regulation of some of the observed genes (TLR3, IL-1β, and IFN-γ) in trachea and lung. This initial down-regulation followed by the induction of innate immune response to IBV infection appears to be inadequate for the control of IBV genome accumulation and consequent histopathological changes in these tissues. Potential induction of innate immunity before infection occurs may be necessary to reduce the consequences since vaccine induced immunity is slow to develop.


title: Simulate_PCR for amplicon prediction and annotation from multiplex, degenerate primers and probes

text: BACKGROUND: Pairing up primers to amplify desired targets and avoid undesired cross reactions can be a combinatorial challenge. Effective prediction of specificity and inclusivity from multiplexed primers and TaqMan®/Luminex® probes is a critical step in PCR design. RESULTS: Code is described to identify all primer and probe combinations from a list of unpaired, unordered candidates that should produce a product. It predicts and extracts all amplicon sequences in a large sequence database from a list of primers and probes, allowing degenerate bases and user-specified levels of primer-target mismatch tolerance. Amplicons hit by TaqMan®/Luminex® probes are indicated, and products may be annotated with gene information from NCBI. Fragment length distributions are calculated to predict electrophoretic gel banding patterns. CONCLUSIONS: Simulate_PCR is the only freely available software that can be run from the command line for high throughput applications which can calculate all products from large lists of primers and probes compared to a large sequence database such as nt. It requires no prior knowledge of how primers should be paired. Degenerate bases are allowed and entire amplicon sequences are extracted and annotated with gene information. Examples are provided for sets of TaqMan®/Luminex® PCR signatures predicted to amplify all HIV-1 genomes, all Coronaviridae genomes, and a group of antibiotic resistance genes. The software is a command line perl script freely available as open source.


title: How to provide an effective primary health care in fighting against severe acute respiratory syndrome: The experiences of two cities

text: OBJECTIVES: This study was designed to compare the response and management of severe acute respiratory syndrome (SARS) by the family physicians of the Hong Kong and the Toronto health systems, and to provide evidence to improve health policy and practices in a newly emerging infectious disease. METHODS: A questionnaire was sent to family medicine tutors affiliated with either the Chinese University of Hong Kong or the University of Toronto in 2003. The survey questions covered training for SARS, the use of screening tools, an anxiety scale, clinical practices, and demographic data. RESULTS: 137 (74.8%) and 51 (34%) doctors from Hong Kong and Toronto replied to the questionnaire, respectively. Most (80-84.6%) had no training in infectious disease control and were not confident in dealing with SARS (68.1-73.5%). In Hong Kong, the screening tools provided by international agencies did not meet the local needs. In Toronto, lack of a centralized hospital admission policy and fully public laboratory probably resulted in appointment cancellation and dissatisfaction. There may be a need for deployment of personnel between institutions but loss of income was not a major concern. CONCLUSIONS: Sharing the “lessons learned” in different regions during a SARS outbreak will help prepare for the next epidemic.


title: Coronaviruses in wastewater processes: source, fate and potential risks

text: Abstract The last 17 years have seen three major outbreaks caused by coronaviruses, with the latest outbreak, COVID-19, declared a pandemic by the World Health Organization. The frequency of these outbreaks, their mortality and associated disruption to normal life calls for concerted efforts to understand their occurrence and fate in different environments. There is an increased interest in the occurrence of coronaviruses in wastewater from the perspective of wastewater-based epidemiology. However, there is no comprehensive review of the knowledge on coronavirus occurrence, fate and potential transmission in wastewater. This paper, provides a review of the literature on the occurrence of coronaviruses in wastewater treatment processes. We discuss the presence of viral RNA in feces as a result of gastrointestinal infections resulting in diarrhoea. We also review the literature on their presence, survival and potential removal in common wastewater treatment processes. The detection of infectious viral particles in feces of patients raises questions on the potential risks of infection for people exposed to untreated sewage/wastewater. We, therefore, discuss the potential risk of infection with coronaviruses for workers in wastewater treatment plants and the public that may be exposed through faulty plumbing or burst sewer networks. The disruption of life and mortalities warrants a much more focused research on the role of environments, such as wastewater and surface water, in disease transmission. The current wealth of knowledge on coronaviruses in wastewater based on the reviewed literature is scant and therefore calls for further studies.


title: Infection control and prevention practices implemented to reduce transmission risk of Middle East respiratory syndrome-coronavirus in a tertiary care institution in Saudi Arabia

text: BACKGROUND: Transmission of Middle East respiratory syndrome-coronavirus (MERS-CoV) among health care workers (HCWs) and patients has been documented with mortality rate approximating 36%. We propose advanced infection control measures (A-IC) used in conjunction with basic infection control measures (B-IC) help reduce pathogen transmission. B-IC include standard and transmission-based precautions. A-IC are initiatives implemented within our center to enhance effectiveness of B-IC. OBJECTIVE: Study effectiveness of combining B-IC and A-IC to prevent transmission of MERS-CoV to HCWs. METHODS: A retrospective observational study was undertaken. A-IC measures include administrative support with daily rounds; infection control risk assessment; timely screening, isolation, and specimen analysis; collaboration; epidemic planning; stockpiling; implementation of contingency plans; full personal protective equipment use for advanced airway management; use of a real-time electronic isolation flagging system; infection prevention and control team on-call protocols; pretransfer MERS-CoV testing; and education. RESULTS: A total of 874 real-time polymerase chain reaction MERS-CoV tests were performed during the period beginning July 1, 2013, and ending January 31, 2015. Six hundred ninety-four non-HCWs were tested, of these 16 tested positive for MERS-CoV and their infection was community acquired. Sixty-nine percent of the confirmed MERS-CoV-positive cases were men, with an average age of 56 years (range, 19-84 years). Of the total tested for MERS-CoV, 180 individuals were HCWs with zero positivity. CONCLUSIONS: Adhering to a combination of B-IC and A-IC reduces the risk of MERS-CoV transmission to HCWs.


title: Asthma associated with denatonium benzoate in a healthcare worker in Taiwan: A case report

text: RATIONALE: Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable. PATIENT CONCERNS: A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium). DIAGNOSES: Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma. INTERVENTIONS: This patient was treated with omalizumab (Xolair), corticosteroid, β(2) agonist, montelukast, and Symbicort turbuhaler. OUTCOMES: The patient showed quick responses after treatment with diphenhydramine (intramuscularly), fenoterol HBr (inhalation), and prednisolone (oral). Approximately 2 weeks later, she suffered from difficulty breathing and asthmatic symptoms again when she was exposed to polished wax and disinfectant. She was treated with omalizumab (Xolair), corticosteroid, β(2) agonist, montelukast, and Symbicort turbuhaler. The patient was in stable condition with improvement in symptoms during follow-up. LESSONS: There may be potentially important health risks when healthcare workers are exposed to denatonium benzoate. Individuals who have a history of allergy to disinfecting products (containing quaternary ammonium) should avoid exposure of denatonium benzoate. More advanced research is needed in the future.


docid: jildjowc

title: Binding characterization of determinants in porcine aminopeptidase N, the cellular receptor for transmissible gastroenteritis virus

text: Abstract Four truncated porcine aminopeptidase N (pAPN, a cellular receptor for porcine coronaviruses) proteins were expressed in prokaryotic cells. The recognizing of a specific serum against pAPN to these proteins was investigated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The binding ability of the proteins to transmissible gastroenteritis virus (TGEV), a porcine coronavirus, was analyzed by ELISA. The inhibitory effect of these proteins to cell infection by TGEV was analyzed using plaque assays. Our data indicate that three truncated pAPNs positively reacted with the specific antiserum and the major binding regions of pAPN were limited in regions 36aa–223aa, 349aa–591aa and 592–963aa. The proteins showed discrepant binding activity to either pAPN antibody or TGE virions. Moreover, the truncated proteins blocked the infection of cells by TGEV to different extent. The results suggest that the major antibody-binding domains of pAPN may associate with the receptor-binding determinants. The role of APN is discussed in the context of virus receptor usage.


title: One Health: The Hong Kong Experience with Avian Influenza

text: The occurrence of avian influenza A(H5N1) in Hong Kong in 1997 led to the development of a “One-Health” approach to deal with emerging infectious diseases that has been applied to other emergent diseases such as SARS and the pandemic H1N1 2009. Evaluation of poultry marketing and production systems and investigations at the animal-human interface, led to defining the routes of human exposure to avian influenza and factors that allowed virus to multiply and persist. Active and systematic surveillance of apparently healthy as well as diseased poultry and wild birds provided evidence of ongoing virus evolution in the wider region. Epidemiological studies, supplemented with molecular epidemiology, helped to elucidate the role of the poultry marketing system and live poultry markets in the persistence of avian influenza viruses and provided evidence for the impact of interventions designed to interrupt virus transmission. Enhanced bio-security, active surveillance together with targeted and evidence-based interventions in the poultry production, and marketing system together with poultry vaccination has prevented further human H5N1 disease and minimized outbreaks of poultry disease in Hong Kong. Similar strategies have led to the understanding of the emergence of SARS and provided options for preventing the re-emergence of this disease. Surveillance of influenza in swine has provided insights into the emergence of the 2009 pandemic, to the reverse zoonosis of the pandemic virus from humans to swine and to the emergence of novel reassortant viruses within swine. “One Health” strategies are not “cost-free” and require sensitive implementation to optimize food-safety and food security, while safeguarding the economics of animal husbandry and the environment and remaining sensitive to cultural practices.


title: The close genetic relationship of lineage D Betacoronavirus from Nigerian and Kenyan straw-colored fruit bats (Eidolon helvum) is consistent with the existence of a single epidemiological unit across sub-Saharan Africa

text: Straw-colored fruit bats (Eidolon helvum), which have been identified as natural hosts for several zoonotic pathogens, such as lyssaviruses, henipaviruses, and ebolavirus, are associated with human settlements in Nigeria where they are commonly consumed as a delicacy. However, information on the viruses harbored by these bats is scarce. In this study, coronavirus sequences were detected using a nested RT-PCR targeting 440 bp of the RNA-dependent RNA polymerase (RdRp) in six of 79 fecal samples collected from an urban colony of E. helvum in Ibadan, Nigeria. Phylogenetic analysis revealed that all six sequences were monophyletic and clustered in lineage D of Betacoronavirus. The extension of two fragments allowed us to classify our sequences within the RdRp Group Unit defined for Kenyan Betacoronavirus from the same host species. These findings are consistent with the previous suggestion on the existence of a single epidemiological unit of E. helvum across sub-Saharan Africa. This theory, which is supported by the genetic structure of continental E. helvum, could facilitate viral mixing between different colonies across the continent.


Deficiencies in Global Health Training for Cardiovascular Fellows


Please cite this paper as: Huijskens et al. (2012) Viral and bacterial aetiology of community‐acquired pneumonia in adults. Influenza and Other Respiratory Viruses 7(4), 567–573. Background Modern molecular techniques reveal new information on the role of respiratory viruses in community‐acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community‐acquired pneumonia who were admitted to the hospital. Methods Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community‐acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real‐time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. Results Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were positive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (≥2) were found in 16 patients. Conclusion In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.


title: Animal models for SARS and MERS coronaviruses

text: The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV.


title: Coronavirus JHM: nucleotide sequence of the mRNA that encodes nucleocapsid protein.

text: A DNA copy of the mRNA that encodes the nucleocapsid protein of Mouse Hepatitis Virus JHM has been cloned into pAT153. The DNA copy specifically inhibited the synthesis in vitro of the nucleocapsid protein. The cDNA was subcloned into M13 vectors and the entire sequence, 1767 bases including a 15 base terminal poly (A) tract, has been determined by chain-terminator sequencing. The sequence contained an open-reading frame that could encode a basic protein of mol.wt. 49700. From the predicted sequence it was apparent that the nucleocapsid protein has 5 basic regions, two of which are located near the middle of the sequence, a serine-rich region was also located, a feature which may be of functional importance as the nucleocapsid protein is phosphorylated at serine residues. The carboxy terminus of the nucleocapsid protein was found to be acidic. The 5' non-coding sequence contained a triple repeat of the pentamer AATCT, a structural feature which may play a significant role during the production of subgenomic viral mRNAs.


docid: xcwppaux

title: Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood

text: This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies.


title: Viral metagenomics of six bat species in close contact with humans in southern China

text: Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3570-3) contains supplementary material, which is available to authorized users.


title: Neonatal Foal Diarrhea

text: Diarrhea is a significant cause of morbidity and mortality in the neonatal foal. Numerous noninfectious and infectious agents are responsible for enterocolitis and enteritis. This article provides an overview of the differential diagnoses for neonatal diarrhea and general and specific guidelines for therapy.


title: Zoonoses

text: Zoonoses are the “diseases and infections that are naturally transmitted between vertebrate animals and man,” as defined in 1951 by the World Health Organization (WHO) Expert Committee on Zoonoses. The word zoonosis (plural zoonoses) is the combination of two Greek words (zoon, animals and noson, disease), and was coined at the end of the nineteenth century by Rudolph Virchow to designate human diseases caused by animals. Nevertheless, the term should also include vertebrate animal diseases caused by exposure to humans, such as measles in nonhuman primates, which is of major concern in any major primate center. The term ‘zoonosis’ is also considered to be shorter and more convenient than ‘anthropozoonosis’ (animals to humans) and ‘zooanthroponosis’ (humans to animals), which are based on the prevailing direction of transmission between humans and other vertebrates.


title: Immune response induced by spike protein from transmissible gastroenteritis coronavirus expressed in mouse mammary cells

text: Abstract The present study is undertaken to investigate the immune response that was induced by the recombinant spike (S) protein from swine-transmissible gastroenteritis virus (TGEV) expressed in mouse mammary cells. A mammary-specific expression vector pEBS containing the full-length cDNA of S gene was constructed and expressed in the mouse mammary cells (EMT6). The recombinant S protein from culture supernatant of transgenic EMT6 was harvested and immunized BALB/c mice. The results demonstrated recombinant S protein was expressed at high levels in mammary cells by Western blotting and enzyme-linked immunosorbent assay (ELISA) detection. The antibody titer in BALB/c mice following immunization with recombinant S protein was detectable after the first immunization. Maximum titers of antibody (8.86±0.19ng/ml of serum) were attained after the second immunization. In conclusion, the recombinant S protein expressed in mammary cells was able to elicit substantial immunological response against TGEV. This lays the basis for using mammary gland bioreactor generating edible vaccine.


title: Surgical telemedicine here to stay: More support from a randomized controlled trial on postoperative surgery visits

text: • Telemedicine and their studied elements. • Reference to large review articles including numerous surgical studies reviewing telemedicine. •Association of Telemedicine adoption and COVID-19.


title: A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital

text: Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks’ treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.


title: Gene transfer in higher animals: theoretical considerations and key concepts

text: Gene transfer technology provides the ability to genetically manipulate the cells of higher animals. Gene transfer permits both germline and somatic alterations. Such genetic manipulation is the basis for animal transgenesis goals and gene therapy attempts. Improvements in gene transfer are required in terms of transgene design to permit gene targeting, and in terms of transfection approaches to allow improved transgene uptake efficiencies.


title: Utility and risk of dermatologic medications during the COVID‐19 pandemic

text: In the era of staggering speed in development of the novel coronavirus (CoV) pandemic (COVID‐19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV2), we have reviewed the dermatologists’ tools at hand for their utility (and potential risks) in patients affected by COVID‐19. This review aims to shed light on the anti‐viral and pro‐viral potential of drugs routinely used in dermatology to modulate COVID‐19. The literature search included peer‐reviewed articles published in English language (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) from January 1990 to March 2020 and by reference lists of respective articles. Somewhat to our surprise, we have found that several of our drugs widely used in dermatology have antiviral potential. On the other hand, we also frequently use immunosuppressive drugs in our dermatologic patients that potentially pose them at increased risk for COVID‐19. This article is protected by copyright. All rights reserved.


title: Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays

text: Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis. Methods: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells. Results: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells. Conclusion: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.


Adapting mental health care after the COVID-19 outbreak: preliminary findings from a public general hospital in Madrid (Spain)


title: Identification of enterobacteria in viscera of pigs afflicted with porcine reproductive and respiratory syndrome and other viral co-infections

text: In order to investigate enterobacteria presence involved in the secondary infections in Porcine Reproductive and Respiratory Syndrome (PRRS) pigs with different viral co-infections, we identified enterobacteria for guiding clinical treatment. Twenty-one diseased pigs were diagnosed with the PRRS virus (PRRSV) and other 7 virus primers by PCR/RT-PCR in the lung and spleen samples. Enterobacteria were isolated using MacConkey agar from 5 visceral samples of PRRS pigs, and identified by 16S rDNA sequencing. PRRSV was positive in 100% of the lung samples and 81.0% of the spleen samples. Seven diseased pigs were diagnosed with only PRRSV infection (33.3%), 7 pigs with PRRSV and 1 or 2 other viruses (33.3%) and 7 pigs with PRRSV and more than 2 types of other viruses (33.3%). PRRSV was more inclined to co-infect pigs with porcine group A rotavirus (PARV) with the co-infection rate of 52.4% (11/21). Approximately 13 types of bacteria were successfully isolated from lung, spleen, liver, kidney and lymph node samples of different PRRS pigs. Enterobacteria were isolated in 100% of lung, liver and lymph samples from pigs infected with PRRSV alone. However, the isolation rates were significantly decreased in the more than 3 viruses co-infection group. Escherichia coli was the most prevalent bacterium, followed by Morganella, Proteus, Shigella, Salmonella, Klebsiella and Aeromonas. Most of the isolated enterobacteria were opportunistic pathogens. Therefore, timely combination with antimicrobial agents is necessary for effective treatment of PRRS-infected pigs.


title: Raman Spectroscopy Based Detection of RNA viruses in Saliva: a preliminary report

text: Several non‐invasive Raman spectroscopy‐based assays have been reported for rapid and sensitive detection of pathogens. We developed a novel statistical model for the detection of RNA viruses in saliva, based on an unbiased selection of a set of 65 Raman spectral features that mostly attribute to the RNA moieties, with a prediction accuracy of 91.6% (92.5 % sensitivity and 88.8 % specificity). Furthermore, to minimize variability and automate the downstream analysis of the Raman spectra, we developed a GUI based analytical tool ‘RNA Virus Detector (RVD)‘. This conceptual framework to detect RNA viruses in saliva could form the basis for field application of Raman Spectroscopy in managing viral outbreaks, such as the ongoing COVID‐19 pandemic. (http://www.actrec.gov.in/pi‐webpages/AmitDutt/RVD/RVD.html). This article is protected by copyright. All rights reserved.


title: Validation of the Provincial Transfer Authorization Centre database: a comprehensive database containing records of all inter-facility patient transfers in the province of Ontario

text: BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established as a part of the emergency response in Ontario, Canada to the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to inter-facility patient transfers were not collected in a systematic manner. Then, in an emergency setting, a comprehensive database with a complex data collection process was established. For the first time in Ontario, population-based data for patient movement between healthcare facilities for a population of twelve million are available. The PTAC database stores all patient transfer data in a large database. There are few population-based patient transfer databases and the PTAC database is believed to be the largest example to house this novel dataset. A patient transfer database has also never been validated. This paper presents the validation of the PTAC database. METHODS: A random sample of 100 patient inter-facility transfer records was compared to the corresponding institutional patient records from the sending healthcare facilities. Measures of agreement, including sensitivity, were calculated for the 12 common data variables. RESULTS: Of the 100 randomly selected patient transfer records, 95 (95%) of the corresponding institutional patient records were located. Data variables in the categories patient demographics, facility identification and timing of transfer and reason and urgency of transfer had strong agreement levels. The 10 most commonly used data variables had accuracy rates that ranged from 85.3% to 100% and error rates ranging from 0 to 12.6%. These same variables had sensitivity values ranging from 0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional patient records and the PTAC data for fields compared in this study supports the validity of the PTAC database. For the first time, a population-based patient transfer database has been established. Although it was created during an emergency situation and data collection is dependent on front-line medical workers, the PTAC data has achieved a high level of validity, perhaps even higher than many purpose built databases created during non-emergency settings.


docid: xbjeaidl

title: Covid-19 face masks: A potential source of microplastic fibers in the environment

text: [Figure: see text]


title: The impact of COVID-19 on neurosurgeons and the strategy for triaging non-emergent operations: a global neurosurgery study

text: OBJECT: The COVID-19 pandemic has disrupted all aspects of society globally. As healthcare resources had to be preserved for infected patients, and the risk of in-hospital procedures escalated for uninfected patients and staff, neurosurgeons around the world have had to postpone non-emergent procedures. Under these unprecedented conditions, the decision to defer cases became increasingly difficult as COVID-19 cases skyrocketed. METHODS: Data was collected by self-reporting surveys during two discrete periods: the principal survey accrued responses during 2 weeks at the peak of the global pandemic, and the supplemental survey accrued responses after that to detect changes in opinions and circumstances. Nine hypothetical surgical scenarios were used to query neurosurgeons’ opinion on the risk of postponement and the urgency to re-schedule the procedures. An acuity index was generated for each scenario, and this was used to rank the nine cases. RESULTS: There were 494 respondents to the principal survey from 60 countries. 258 (52.5%) reported that all elective cases and clinics have been shut down by their main hospital. A total of 226 respondents (46.1%) reported that their operative volume had dropped more than 50%. For the countries most affected by COVID-19, this proportion was 54.7%. There was a high degree of agreement among our respondents that fast-evolving neuro-oncological cases are non-emergent cases that nonetheless have the highest risk in postponement, and selected vascular cases may have high acuity as well. CONCLUSION: We report on the impact of COVID-19 on neurosurgeons around the world. From their ranking of the nine case scenarios, we deduced a strategic scheme that can serve as a guideline to triage non-emergent neurosurgical procedures during the pandemic. With it, hopefully, neurosurgeons can continue to serve their patients without endangering them either neurologically or risking their exposure to the deadly virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00701-020-04342-5) contains supplementary material, which is available to authorized users.


title: COL02-02: Intérêt de la recherche de virus respiratoires par PCR multiplex dans les pneumopathies communautaires de l’adulte vu aux urgences – protocole PACSCAN

text: Introduction – objectifs Le diagnostic des pneumopathies communautaires (PAC) de l’adulte vu aux urgences repose essentiellement sur la clinique et la radiologie. Le rôle exact des agents viraux dans ces pneumopathies est mal connu. Objectifs – Identifier les virus circulants chez les patients (pts) suspects de PAC vus aux urgences – étudier la corrélation entre la présence de ces agents infectieux et le diagnostic clinique de PAC ; Matériels et méthodes Un prélèvement nasal et pharyngé a été réalisé chez des pts adultes inclus dans le protocole PACSCAN (impact du scanner dans le diagnostic de PAC) pour suspicion de PAC dans quatre services d’urgences de CHU parisiens. Une PCR multiplex détectant 15 virus (Grippe A/B, H1N1, VRS A, B, Parinfluenzae (1 à 4), Adénovirus, 3 Coronavirus, Metapneumovirus, Rhinovirus), et 4 bactéries (Mycoplsma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Bordetella pertussis), a été réalisée en aveugle sur chaque prélèvement. Le diagnostic clinique de PAC a été validé par un comité d’experts indépendants. Résultats Parmi les 254 pts prélevés en novembre 2011-décembre 2012, 78 (31 %) pts avaient une PCR positive, avec un seul (75,96 %) ou plusieurs (3, 4 %) agent infectieux (bactéries ou virus). Les virus les plus fréquemment identifiés étaient les virus de la grippe (35 %) et les Rhinovirus (26 %). Les prélèvements de routine détectaient une bactérie chez 31/190 (16 %) pts. 18/78 (23 %) pts avec PCR positive avaient un score FINE IV ou V plus faible que chez les pts PCR négatives (39 %) (p=0.001). Contrairement aux virus Influenza, la proportion de Rhinovirus, était plus faible chez les pts ayant un diagnostic de PAC que chez ceux dont la PAC était exclue (p<0.01). Conclusion L’implication des virus respiratoires dans les PAC n’est pas négligeable, Une analyse conjuguée clinique, radiologique et virologique peut permettre


title: Antimicrobial, Antiviral and Immunomodulatory Activity Studies of Pelargonium sidoides (EPs(®) 7630) in the Context of Health Promotion

text: Pelargonium species contribute significantly to the health care of a large population in the Southern African region, as part of a long-standing medical system intimately linked to traditional healing practices. Most notably, extracts of the roots of P. sidoides have commonly been applied for the treatment of dysentery and diarrhoea but only occasionally for respiratory complaints. Clinical trials have shown that a modern aqueous-ethanolic formulation of P. sidoides extracts (EPs(®) 7630) is an efficacious treatment for disorders of the respiratory tract, for example bronchitis and sinusitis. It should be noted that EPs(®) 7630 is the most widely investigated extract and therefore is the focus of this review. In order to provide a rationale for its therapeutic activity extracts have been evaluated for antibacterial activity and for their effects on non-specific immune functions. Only moderate direct antibacterial capabilities against a spectrum of bacteria, including Mycobacteria strains, have been noted. In contrast, a large body of in vitro studies has provided convincing evidence for an anti-infective principle associated with activation of the non-specific immune system. Interestingly, significant inhibition of interaction between bacteria and host cells, a key to the pathogenesis of respiratory tract infections, has emerged from recent studies. In addition, antiviral effects have been demonstrated, including inhibition of the replication of respiratory viruses and the enzymes haemagglutinin and neuraminidase. Besides, an increase of cilliary beat frequency of respiratory cells may contribute to the beneficial effects of P. sidoides extracts. This example provides a compelling argument for continuing the exploration of Nature and traditional medical systems as a source of therapeutically useful herbal medicines.


title: In Case You Haven't Heard…

text: Among the misinformation spread on social media is the idea that cocaine can fight the coronavirus. It's not clear where this is coming from — Russia? The State Department has already blamed Russia for false personas. Garlic and masturbation have been added to the mythology. Whether this is disinformation or misinformation is unclear. But it is playing into everyone's fear. These “cures” are not only not cures; they're dangerous. Well, cocaine is at least.


title: Reorganization of Medical Oncology Departments during COVID-19 Pandemic: a Nationwide Italian Survey

text: Abstract The novel severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) pandemic is a global health problem, which started to affect China by the end of year 2019. In Europe, Italy has faced this novel disease entity (named COVID-19) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits, and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during pandemic.


title: New and emerging infectious diseases

text: New and emerging diseases present a constant challenge. Globalization of business, international adoption, immigration, and tourism have contributed to the rapid spread of diseases, such as severe acute respiratory syndrome (SARS). Infectious diseases that emerge in Africa or Asia may arrive on US shores within days. This article reviews the new and emerging pathogens important to dermatologists.


title: Anvillea garcinii extract inhibits the oxidative burst of primary human neutrophils

text: BACKGROUND: Anvillea garcinii Coss. & Durieu (Anv) plant is used as a traditional North African medicine against several diseases associated with inflammation. At inflammatory sites, reactive oxygen species (ROS) produced in excess by activated phagocyte NADPH oxidase (NOX2) can accentuate inflammatory responses. Thus, we investigated if Anv-water soluble polysaccharides could modulate primary human neutrophil oxidative burst in vitro. METHODS: Human neutrophils were isolated from fresh whole blood and O(2) (.-) generation was measured by cytochrome c reduction assays. Western blots were used to analyse the translocation of PKC, p47(phox) (a key component of NOX2 activity) to neutrophil plasma membrane. Also, myeloperoxidase (MPO) release in the extracellular medium was studied by western blots. Flow cytometric analysis was used to detect CD11b membrane expression. RESULTS: Water soluble polysaccharides from Anv dose-dependently inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLF)- and phorbol myristate acetate (PMA)-induced O(2) (.-) generation by human neutrophils. Moreover, Anv-polysaccharides strongly inhibited PMA-induced PKCβ and p47(phox) translocation to membranes and p47(phox) phosphorylation on Ser328, a main PKC target. In contrast, polysaccharides extract from Zygophyllum gaetulum plant, which is also used as a traditional North African medicine against inflammatory diseases, was ineffective on this PKCβ-p47phox pathway. Further, Anv inhibited important neutrophil degranulation markers corresponding to myeloperoxidase (MPO) release and CD11b membrane expression. CONCLUSION: The process of down-regulating NADPH oxidase by polysaccharides extracts from Anv provides new insights into the mechanism of Anv’s anti-inflammatory actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1411-7) contains supplementary material, which is available to authorized users.


title: “COVID-19 y estudios microbiológicos post mortem”

text: Resumen En este artículo se revisan los aspectos microbiológicos de la infección COVID-19 y se presentan las recomendaciones sobre los análisis que deben realizarse en casos forenses. En primer lugar, se analizan las características taxonómicas del virus, su relación con la familia coronaviridae y su estructura genética. Se presentan brevemente las características clínicas y patológicas de la infección COVID-19 así como las coinfecciones que pueden asociarse a este virus. En el diagnóstico de laboratorio se describe la PCR, técnica de elección en la fase aguda de la infección; los estudios antigénicos y los serológicos. Finalmente se detallan los principales objetivos para los estudios microbiológicos en fallecidos en relación a la pandemia COVID-19 y se describen los principales análisis microbiológicos post- mórtem a realizar en fallecidos en el ámbito forense. Los estudios microbiológicos deben estar dirigidos tanto a la detección del SARS-CoV-2 como de las coinfecciones, que también podrían contribuir a la causa de muerte. Abstract We review the microbiological aspects of COVID-19 infection and present the microbiological studies that should be performed in forensic cases. We describe the taxonomic characteristics of the virus, its relationship with the coronaviridae family and its genetic structure. We briefly present the clinical and pathological characteristics of COVID-19 infection, as well as the co-infections that could be associated with this virus. In the laboratory, PCR is a first-choice technique in the acute phase of the infection, together with antigen and serological studies. Finally, we describe the main objectives of microbiological studies in the deceased in relation to the COVID-19 pandemic, as well as the main post-mortem microbiological analysis to be carried out in the medico-legal context. The microbiological analysis should aim to detect both SARS-CoV-2 and coinfections, which may also contribute to the cause of death.


title: Analytical validation of the Sysmex XT‐2000iV for cell counts in canine and feline effusions and concordance with cytologic diagnosis

text: Background: The Sysmex XT‐2000iV is a hematology analyzer that combines laser and impedance technology. Its usefulness for determining cell counts in canine and feline intracavitary effusions has not yet been studied. Objectives: The objectives of this study were to evaluate the analytical performance of the Sysmex XT‐2000iV for cell counts in effusions from dogs and cats, and to assess correlation with an impedance counter and concordance with diagnoses based on cytologic findings. Methods: Effusions (43 pleural, 23 peritoneal, 6 pericardial) were analyzed from 32 dogs and 34 cats. Total nucleated cell count (TNCC), HCT, and RBC count were determined on the Sysmex and compared with those obtained on an impedance counter (Hemat 8, SEAC). Imprecision, linearity, and limit of detection were determined for the Sysmex. An algorithm was designed using quantitative and qualitative data from the Sysmex to classify the effusions and the results were compared with diagnoses based on cytologic findings. Results: Intra‐assay and interassay coefficients of variation on the Sysmex were variable. Linearity of TNCC was ≥0.993 for dogs and cats, with the exception of effusions from cats with feline infectious peritonitis, which had delta (Δ) TNC values >3.0. In comparison with the Hemat 8, a proportional error was found for TNCC on the Sysmex. Effusion classification based on the algorithm was concordant with that obtained by cytologic examination in 43/72 (60%) samples. Discordant results usually were due to the misclassification of cells with similar morphology (such as mesothelial and carcinoma cells) in Sysmex scattergrams. Conclusion: The Sysmex XT‐2000iV provides a precise and accurate TNCC and has moderate concordance with cytologic findings for classifying canine and feline effusions. Although microscopic examination of effusions is necessary to achieve an accurate diagnosis, the Sysmex can provide preliminary information that may be helpful to cytopathologists.


The Challenging and Amazing Field of Sports Cardiology


title: Virus-Like Particle-Induced Protection Against MRSA Pneumonia Is Dependent on IL-13 and Enhancement of Phagocyte Function

text: The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13–dependent mechanisms.


docid: fgahetfx

title: Paediatric emergency department visits fell by more than 70% during the COVID‐19 lockdown in Northern Italy

text: In February 2020 the COVID‐19 pandemic flared up across Italy and the first cluster appeared in Southern Lombardy, which is still the most affected area (1). Schools. sports facilities and parks were closed on 1 March, followed by a strict lockdown on 10 March after a significant increase in infections and deaths. The next day the World Health Organization declared COVID‐19 a pandemic. Many studies have now been published concerning the epidemiological and clinical characteristics of COVID‐19 patients, but data on children are still relatively scarce.


title: Rapid Communication: Subclinical bovine respiratory disease – loci and pathogens associated with lung lesions in feedlot cattle

text: Bovine respiratory disease (BRD) is an economically important disease of feedlot cattle that is caused by viral and bacterial pathogen members of the BRD complex. Many cases of subclinical BRD go untreated and are not detected until slaughter, when lung lesions are identified. The objectives of this study were to identify which BRD pathogens were associated with the presence of lung lesions at harvest and to identify genomic loci that were associated with susceptibility to lung lesions as defined by consolidation of the lung and/or the presence of fibrin tissue. Steers from a Colorado feedlot (n = 920) were tested for the presence of viral and bacterial pathogens using deep pharyngeal and mid-nasal swabs collected on entry into the study. Pathogen profiles were compared between cattle with or without lung consolidation (LC), fibrin tissue in the lung (FT), a combination of LC and FT in the same lung (lung lesions [LL]), and hyperinflated lungs (HIF) at harvest. Genotyping was conducted using the Illumina BovineHD BeadChip. Genomewide association analyses (GWAA) were conducted using EMMAX (efficient mixed-model association eXpedited), and pseudoheritabilities were estimated. The pathogen profile comparisons revealed that LC (P = 0.01, odds ratio [OR] = 3.37) and LL cattle (P = 0.04, OR = 4.58) were more likely to be infected with bovine herpes virus-1 and that HIF cattle were more likely to be infected with Mycoplasma spp. (P = 0.04, OR = 4.33). Pseudoheritability estimates were 0.25 for LC, 0.00 for FT, 0.28 for LL, and 0.13 for HIF. Because pseudoheritability for FT was estimated to be 0, GWAA results for FT were not reported. There were 4 QTL that were moderately associated (P < 1 × 10(−5)) with only LC, 2 that were associated with only LL, and 1 that was associated with LC and LL. Loci associated with HIF included 12 that were moderately associated and 3 that were strongly associated (uncorrected P < 5 × 10−7). A 24-kb region surrounding significant lead SNP was investigated to identify positional candidate genes. Many positional candidate genes underlying or flanking the detected QTL have been associated with signal transduction, cell adhesion, or gap junctions, which have functional relevance to the maintenance of lung health. The identification of pathogens and QTL associated with the presence of lung abnormalities in cattle exhibiting subclinical BRD allows the identification of loci that may not be detected through manifestation of clinical disease alone.


Virus etiology of SARI cases and protective role of influenza vaccination determined in sentinel surveillance system


title: Ethical Issues in Radiation Oncology During a Pandemic

text: Medicine in the United States has generally followed ethical principles espoused by Immanuel Kant where the individual patient takes priority in decision-making. With the advent of coronavirus disease 2019 as a major health event, radiation oncologists in some situations need to alter the manner in which they act with individual patients. The well-being of health care workers and society as a whole needs to be considered in management decisions. During the time of a pandemic, ethics principles may be based more on a utilitarian approach that emphasizes the common good. Thus, at times treatment decisions might result in delays in initiating therapy, modifying the radiation treatment course (such as to a short course rather than a long course of therapy), and the sequence of therapies, all to minimize viral exposure. It is important that altered therapy is based as much as possible on institutional or departmental decisions and, to the extent possible, not on a case-by-case basis. However, in all situations, we need to still respect the individual's autonomy and fully inform patients of our decisions and the reasons for those decisions.


docid: eyvaazfj

title: Refinement of long-term toxicity and carcinogenesis studies()

text: The chance that alternatives will completely replace animals for toxicology research in the foreseeable future is nil. Continual refinement of animal toxicity and carcinogenesis studies, however, can be an effective means of reducing the numbers of animals used and conserving time and resources without compromising scientific quality. We must continue to strive to find species and strains that can metabolize chemicals similar to humans, are small enough to be housed in large numbers, and have low prevalence of spontaneous lesions with sufficient life span to express the toxic and carcinogenic potential of chemicals. Adequate care of animals with control of variables such as light, temperature, diet, bedding, diseases, and genetic characters of laboratory animals will decrease the variability. Humane considerations and euthanasia of animals with large masses and other conditions interfering with eating and drinking, major injuries and ulcers related to husbandry and treatment, and diseases indicating pain and suffering will help not only to alleviate further pain and distress but also to facilitate collection of tissues without secondary complications for detection of chemical treatment-related lesions. Limiting the duration of studies to decrease the variability due to ageassociated changes will also refine long-term studies. Other considerations for refinement of carcinogenesis studies include selection of the most sensitive sex of one or more species for evaluation of selected chemicals in a class where toxic and carcinogenic potential of other representative chemicals are known. Genetically engineered animal models with known oncogenes may reduce the duration and increase the sensitivity of carcinogenesis studies with a reduction in the use of animals.


title: Hajj: infectious disease surveillance and control

text: Summary Religious festivals attract a large number of pilgrims from worldwide and are a potential risk for the transmission of infectious diseases between pilgrims, and to the indigenous population. The gathering of a large number of pilgrims could compromise the health system of the host country. The threat to global health security posed by infectious diseases with epidemic potential shows the importance of advanced planning of public health surveillance and response at these religious events. Saudi Arabia has extensive experience of providing health care at mass gatherings acquired through decades of managing millions of pilgrims at the Hajj. In this report, we describe the extensive public health planning, surveillance systems used to monitor public health risks, and health services provided and accessed during Hajj 2012 and Hajj 2013 that together attracted more than 5 million pilgrims from 184 countries. We also describe the recent establishment of the Global Center for Mass Gathering Medicine, a Saudi Government partnership with the WHO Collaborating Centre for Mass Gatherings Medicine, Gulf Co-operation Council states, UK universities, and public health institutions globally.


title: Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial

text: BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.


title: The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) infects host cells with its surface glycosylated spike-protein (S-protein). Here we expressed the SARS-CoV S-protein to investigate its interactions with innate immune mechanisms in the lung. The purified S-protein was detected as a 210kDa glycosylated protein. It was not secreted in the presence of tunicamycin and was detected as a 130kDa protein in the cell lysate. The purified S-protein bound to Vero but not 293T cells and was itself recognized by lung surfactant protein D (SP-D), a collectin found in the lung alveoli. The binding required Ca2+ and was inhibited by maltose. The serum collectin, mannan-binding lectin (MBL), exhibited no detectable binding to the purified S-protein. S-protein binds and activates macrophages but not dendritic cells (DCs). It suggests that SARS-CoV interacts with innate immune mechanisms in the lung through its S-protein and regulates pulmonary inflammation.


title: Nursing Students as Epidemiologists: A Simulation Approach

text: Abstract Simulation is commonly used in nursing education to teach clinical skills. Here, we describe the development processes, implementation, and evaluation of an epidemiology simulation used in a community and public health nursing undergraduate clinical course at the University of Pennsylvania. The simulation was designed to teach students the principles and concepts of outbreak investigation and was based on the 2003 Severe Acute Respiratory Syndrome outbreak in Toronto, Canada. The simulation places students in the role of a public health nurse in the outbreak investigation team, working in groups of five to seven students to complete analyses and make recommendations under time and information constraints. Since piloting in spring 2014, we have run the simulation three times (summer and fall 2014 and summer 2015). Student evaluations show high levels of engagement and interest and substantial increase in the skills and expertise required in an outbreak investigation. We share key lessons learned, including resources required for simulation development and delivery, revisions to the simulation format and content in response to student feedback, and transferability and sustainability of the simulation. Overall, simulation was a feasible and effective modality to teach epidemiology and should be considered in community and public health nursing courses.


title: Bronchiolitis and asthma: Possible common pathogenetic pathways

text: Abstract A discussion of possible mechanisms for virus-induced wheezing in normal and asthmatic children is presented. Presently attractive theories for immune injury in viral bronchiolitis include those which depend on pathology induced by types 1, 3, and 4 of Gell and Coombs. The continuum of viral bronchiolitis with virus-induced wheezing in young children who are labeled “asthmatic” argues for some common mechanism of bronchiolar obstruction.


title: One health approach in Nepal: Scope, opportunities and challenges

text: One Health (OH) is a collaborative effort to attain optimal health for people, animals and the environment. The concept of OH is still in its infancy in Nepal but is increasingly growing. The Government of Nepal (GoN) has taken some initiatives to tackle burgeoning problems such as antimicrobial resistance, highly pathogenic avian influenza and rabies using OH approach but there are several challenges at the level of implementation. Few non-governmental organizations support GoN to promote an OH approach. The major bottlenecks in implementing OH in Nepal include poor organizational structure to support OH, absence of a legal framework to implement OH, poor coordination among different governmental agencies, insufficient technical expertise, poor data sharing mechanism across sectors, limited budget and poor understanding at political level. We encourage GoN to address these gaps and prioritize the health problems where OH approach would give the best outcome. Institutional and legal frameworks need to be created to effectively implement an OH approach in Nepal. Increasing awareness among policy makers including political leadership and increasing regular government budget for OH activities would be helpful to promote OH in Nepal.


title: Recovery from COVID‐19 following hepatitis C, human immunodeficiency virus infection, and liver transplantation

text: Immunosuppression and frequent comorbidities in transplant recipients potentially increase the risk of fatal outcomes of pandemic coronavirus disease 2019 (COVID-19) [1]. A 1965 born male had suffered from haemophilia A. In the nineteen-seventies, he acquired hepatitis C virus (HCV) infection, probably via factor VIII supplementation, and in 1985 human immunodeficiency virus (HIV) infection. Interferon-based HCV therapy resulted in a sustained virological response. Antiviral treatment with emtricitabine/tenofovir alafenamide/rilpivirin for HIV is ongoing since 2016. HIV suppression with repeatedly negative PCR results has been achieved.


title: COVID-19 and spinal cord injury and disease: results of an international survey

text: STUDY DESIGN: An online survey. OBJECTIVES: To query the international spinal cord medicine community’s engagement with and response to the novel coronavirus (COVID-19) pandemic and to assess pandemic-specific information needs and patient concerns. SETTING: An international collaboration of authors and participants. METHODS: Two near-identical surveys (one English and one Spanish language) were distributed via the internet. Responses from those questions shared between the surveys were pooled then analyzed; four questions’ responses (those not shared) were analyzed separately. RESULTS: A total of 783 responses were submitted from six continents. Few participants (5.8%) had tested their outpatients with SCI/D for COVID-19; only 4.4% reported having a patient with SCI/D with the virus. Of respondents who worked at an inpatient facility, 53.3% reported that only individuals with symptoms were being screened and 29.9% said that no screening was occurring. Participants relayed several concerns offered by their patients with SCI/D, including vulnerability to infection (76.9%) and fragility of caretaker supply (42%), and those living in countries with guaranteed health care were more likely to report widespread availability of COVID-19 testing than were those living in countries without universal care, χ(2) (3, N = 625) = 46.259, p < 0.001. CONCLUSION: There is substantial variability in the rehabilitation medicine community in COVID-19 screening practices and availability of screening kits. People living with SCI/D are expressing legitimate and real concerns about their vulnerability to COVID-19. More and rapid work is needed to address these concerns and to standardize best-practice protocols throughout the rehabilitation community.


title: Prenatal maternal distress associates with a blunted cortisol response in rhinovirus-positive infants

text: Abstract Introduction Prenatal exposure to maternal psychological distress (PD) may have programming effects on the fetus/infant hypothalamic-pituitary-adrenal (HPA) axis and subsequently on the development of the fetus’ immune function. Therefore, our aim was to study whether prenatal exposure to PD is related to early infant HPA axis reactivity in the context of a subclinical rhinovirus infection that challenges infants HPA axis postnatally. Methods This study included 336 10-week-old infants from the nested case control Focus Cohort of the FinnBrain Birth Cohort Study. The outcome was infant HPA axis reactivity in a stress test. The acute stressor comprised of pediatric examination with venipuncture and nasal swabs for virus assessment. Saliva cortisol samples were collected at 5 time points: baseline, 0, 15, 25 and 35 min after the stressor. HPA axis reactivity was defined by the cumulative post-stressor cortisol concentration. Results HPA axis reactivity was blunted in the PD/rhinovirus + group compared to the average of control/rhinovirus+, PD/rhinovirus-, and control/rhinovirus- groups (difference: 14.7 ln [nmol/L] × min, 95% confidence interval 3.8–25.6, p = .008). HPA axis reactivity was significantly blunted only in boys with rhinovirus detected when separately tested for boys and girls (p = .04). Conclusion Our finding of PD-exposed rhinovirus-positive infants having blunted cortisol secretion gives rise to a hypothesis that maternal PD during pregnancy influences infant HPA axis functioning and the functioning of the immune system. Future studies are needed to test whether this suppression of the HPA axis that co-occurs with rhinovirus infection associates with later disease development (e.g., asthma).


title: Dose–response time modelling for highly pathogenic avian influenza A (H5N1) virus infection

text: Aims: To develop time‐dependent dose–response models for highly pathogenic avian influenza A (HPAI) of the H5N1 subtype virus. Methods and Results: A total of four candidate time‐dependent dose–response models were fitted to four survival data sets for animals (mice or ferrets) exposed to graded doses of HPAI H5N1 virus using the maximum‐likelihood estimation. A beta‐Poisson dose–response model with the N (50) parameter modified by an exponential‐inverse‐power time dependency or an exponential dose–response model with the k parameter modified by an exponential‐inverse time dependency provided a statistically adequate fit to the observed survival data. Conclusions: We have successfully developed the time‐dependent dose–response models to describe the mortality of animals exposed to an HPAI H5N1 virus. The developed model describes the mortality over time and represents observed experimental responses accurately. Significance and Impact of the Study: This is the first study describing time‐dependent dose–response models for HPAI H5N1 virus. The developed models will be a useful tool for estimating the mortality of HPAI H5N1 virus, which may depend on time postexposure, for the preparation of a future influenza pandemic caused by this lethal virus.


Trends in Ambulatory Electronic Consultations During the COVID-19 Pandemic


title: Estimation of the net reproductive number of COVID-19 in Iran

text: Background: Estimating the net reproductive number of COVID-19 virus can reveal the rate and severity of the disease transmission in the Iranian society to health researchers and practitioners. Also, it signifies the importance of the disease to the community. Thus, the aim of this study was to determine the net reproductive number of COVID-19 in Iran and its different provinces. Methods: This study was conducted on the data of COVID-19 patients in Iran from February 21 to March 8, 2020. To determine the net reproductive number of COVID-19 in Iran, the serial interval and β value were first determined using linear regression analysis. Then, the net reproductive number values were calculated for Iran and its different provinces. Results: The results of this study showed that the net reproductive number of COVID-19 in Iran was 1.31. Using the available data up to March 15, 2020, the highest net reproductive number was in Mazandaran, Yazd, Isfahan, Qazvin, and Zanjan provinces, with values of 2.07, 1.86, 1.84, and 1.76, respectively. The net reproductive number also showed an increasing trend in Kohgiluyeh and BoyerAhmad province. Conclusion: It seems that although the net reproductive number of the virus had a decreasing trend in the provinces, it is still high. Therefore, sanitary measures in these provinces should be pursued more seriously. On the other hand, social distancing is a topic that should be taken into consideration, that is, social gatherings and contacts should be avoided as much as possible and strategies and facilities for this action should be developed by the government and health policymakers.


title: Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome

text: Summary In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS.


title: NSFC spurs significant basic research progress of respiratory medicine in China

text: Over the years, research in respiratory medicine has progressed rapidly in China. This commentary narrates the role of the National Natural Science Foundation of China (NSFC) in supporting the basic research of respiratory medicine, summarizes the major progress of respiratory medicine in China, and addresses the main future research directions sponsored by the NSFC.


title: Analysis of Women’s Health Online News Articles Using Topic Modeling

text: OBJECTIVES: This research aimed to understand the popularity of topics in the field of women’s health through analysis of online news articles which were chronologically classified and examined to determine how women’s health and diseases had changed over time. METHODS: Women’s health and disease news articles were collated from a popular news website between 1993 to 2015 and preprocessed using gynecological medical terminology, Korean words and nouns (excluding general nouns not related to women’s healthcare topics). The resultant articles (N = 7,710) were analyzed using the Latent Dirichlet Allocation algorithm and major topics were extracted. Topic trends were analyzed by year and period for women’s health. RESULTS: It was observed that most of the women’s health articles were focused on “Healthcare”, and 9 other topics were identified that represented a relatively small proportion in 1993–2000. In 2001–2005, most of the articles were focused on “Medical Services” and “Dietary Supplements” with some specific topics that peaked people’s interest, as compared to those focused on “Healthcare” in the 1990s. It was also observed that differences in the proportion of each topic was small after 2011. CONCLUSION: Changes in topics related to women’s disease were not clearly distinguished in the 1990s but this changed from 2001where articles related to “women disease” appeared as articles on the topics of various diseases.


title: Risk of transmission of airborne infection during train commute based on mathematical model

text: OBJECTIVE: In metropolitan areas in Japan, train commute is very popular that trains are over-crowded with passengers during rush hour. The purpose of this study is to quantify public health risk related to the inhalation of airborne infectious agents in public vehicles during transportation based on a mathematical model. METHODS: The reproduction number for the influenza infection in a train (R(A)) was estimated using a model based on the Wells-Riley model. To estimate the influence of environmental parameters, the duration of exposure and the number of passengers were varied. If an infected person will not use a mask and all susceptible people will wear a mask, a reduction in the risk of transmission could be expected. RESULTS: The estimated probability distribution of R(A) had a median of 2.22, and the distribution was fitted to a log-normal distribution with a geometric mean of 2.22 and a geometric standard deviation of 1.53, under the condition that there are 150 passengers, and that 13 ventilation cycles per hour, as required by law, are made. If the exposure time is less than 30 min, the risk may be low. The exposure time can increase the risk linearly. The number of passengers also increases the risk. However, R(A) is fairly insensitive to the number of passengers. Surgical masks are somewhat effective, whereas High-Efficiency Particulate Air (HEPA) masks are quite effective. Doubling the rate of ventilation reduces R(A) to almost 1. CONCLUSIONS: Because it is not feasible for all passengers to wear a HEPA mask, and improvement in the ventilation seems to be an effective and feasible means of preventing influenza infection in public trains.


How reliable is clinical assessment in neonatal jaundice? Dear Sir


title: Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

text: Abstract An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.


title: A novel sub-epidemic modeling framework for short-term forecasting epidemic waves

text: BACKGROUND: Simple phenomenological growth models can be useful for estimating transmission parameters and forecasting epidemic trajectories. However, most existing phenomenological growth models only support single-peak outbreak dynamics whereas real epidemics often display more complex transmission trajectories. METHODS: We develop and apply a novel sub-epidemic modeling framework that supports a diversity of epidemic trajectories including stable incidence patterns with sustained or damped oscillations to better understand and forecast epidemic outbreaks. We describe how to forecast an epidemic based on the premise that the observed coarse-scale incidence can be decomposed into overlapping sub-epidemics at finer scales. We evaluate our modeling framework using three outbreak datasets: Severe Acute Respiratory Syndrome (SARS) in Singapore, plague in Madagascar, and the ongoing Ebola outbreak in the Democratic Republic of Congo (DRC) and four performance metrics. RESULTS: The sub-epidemic wave model outperforms simpler growth models in short-term forecasts based on performance metrics that account for the uncertainty of the predictions namely the mean interval score (MIS) and the coverage of the 95% prediction interval. For example, we demonstrate how the sub-epidemic wave model successfully captures the 2-peak pattern of the SARS outbreak in Singapore. Moreover, in short-term sequential forecasts, the sub-epidemic model was able to forecast the second surge in case incidence for this outbreak, which was not possible using the simple growth models. Furthermore, our findings support the view that the national incidence curve of the Ebola epidemic in DRC follows a stable incidence pattern with periodic behavior that can be decomposed into overlapping sub-epidemics. CONCLUSIONS: Our findings highlight how overlapping sub-epidemics can capture complex epidemic dynamics, including oscillatory behavior in the trajectory of the epidemic wave. This observation has significant implications for interpreting apparent noise in incidence data where the oscillations could be dismissed as a result of overdispersion, rather than an intrinsic part of the epidemic dynamics. Unless the oscillations are appropriately modeled, they could also give a false positive, or negative, impression of the impact from public health interventions. These preliminary results using sub-epidemic models can help guide future efforts to better understand the heterogenous spatial and social factors shaping sub-epidemic patterns for other infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1406-6) contains supplementary material, which is available to authorized users.


title: Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi, China

text: Outbreaks of ARD associated with HAdV have been reported in military populations in many countries. Here, we report an ARD outbreak caused by HAdV‐7 in a military training camp in Shaanxi Province, China, from February to March of 2012. Epidemic data and samples from the patients were collected, and viral nucleotides from samples and viral isolations were detected and sequenced. IgG and IgA antibodies against HAdV, and the neutralization antibodies against the viral strain isolated in this outbreak, were detected. Epidemiological study showed that all personnel affected were males with an average age of 19.1 years. Two peaks appeared on the epicurve and there was an 8‐day interval between peaks. Laboratory results of viral nucleotide detection carried out with clinical specimens were positive for HAdV (83.33%, 15/18). Further study through serum antibody assay, virus isolation and phylogenetic analysis showed that HAdV‐7 was the etiological agent responsible for the outbreak. IgA antibody began to appear on the 4th day after the onset and showed 100% positivity on the 8th day. The virus strain in the present outbreak was highly similar to the virus isolated in Hanzhong Shaanxi in 2009. We conclude that HAdV‐7 was the pathogen corresponding to the outbreak, and this is the first report of an ARD outbreak caused by HAdV‐7 in military persons in China. Vaccine development, as well as enhanced epidemiological and virological surveillance of HAdV infections in China should be emphasized.


title: Pex19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis

text: Peroxisomes are components of virtually all eukaryotic cells. While much is known about peroxisomal matrix protein import, our understanding of how peroxisomal membrane proteins (PMPs) are targeted and inserted into the peroxisome membrane is extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes. Furthermore, mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane. This hypothesis is supported by the observation that the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.


docid: qvazsptq

title: Engineering Insights for Multiplexed Real-Time Nucleic Acid Sequence-Based Amplification (NASBA): Implications for Design of Point-of-Care Diagnostics

text: BACKGROUND: Nucleic acid sequence-based amplification (NASBA) offers huge potential for low-cost, point-of-care (POC) diagnostic devices, but has been limited by high false-positive rates and the challenges of primer design. OBJECTIVE: We offer a systematic analysis of NASBA design with a view toward expanding its applicability. METHODS: We examine the parameters that effect dimer formations, and we provide a framework for designing NASBA primers that will reduce false-positive results and make NASBA suitable for more POC diagnostic applications. Then we compare three different oligonucleotide sets to examine (1) the inhibitory effect of dimer formations, (2) false positives with poorly designed primers, and (3) the effect of beacon target location during real-time NASBA. The required T7 promoter sequence adversely affects the reaction kinetics, although the common abridged sequence can improve kinetics without sacrificing accuracy. RESULTS: We demonstrate that poorly designed primers undergo real-time exponential amplification in the absence of target RNA, resulting in false positives with a time to half of the peak value (t (1/2)) of 50 min compared to 45 min for true positives. Redesigning the oligonucleotides to avoid inhibitory dimers eliminated false positives and reduced the true positive t (1/2) by 10 min. Finally, we confirm the efficacy of two molecular beacon design schemes and discuss their multiplexing utility in two clinical scenarios. CONCLUSION: This study provides a pathway for using NASBA in developing POC diagnostic assays. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40291-013-0029-4) contains supplementary material, which is available to authorized users.


Male genitalia injuries: Unspoken collateral damage from the COVID-19 pandemic


title: An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus

text: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 reported SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates. Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea. This tick-borne virus has infected more than 5,000 humans with a 6.4% to 20.9% fatality rate. Currently, there are no prophylactic or therapeutic measures against this virus. Historically, antibodies from patients who recovered from viral infection have been used to treat new patients. Until now, one recombinant monoclonal antibody was approved for the prophylaxis of respiratory syntial virus infection. We selected 10 antibodies from a patient who recovered from SFTS and found that one antibody potently inhibited SFTS viral infection in both test tube and animal studies. We determined the binding site of this antibody to SFTS virus, which allowed us to predict that this antibody could bind 247 out of 272 SFTS virus isolates reported up to now. We anticipate that this antibody could be developed into a therapeutic measure against SFTS.


docid: mrsmwxvo

title: Incidence and viral aetiologies of acute respiratory illnesses (ARIs) in the United States: a population-based study

text: We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42–63] and 35% in Marshfield (95% CI 28–42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.


title: An evolutionary vaccination game in the modified activity driven network by considering the closeness

text: Abstract In this paper, we explore an evolutionary vaccination game in the modified activity driven network by considering the closeness. We set a closeness parameter p which is used to describe the way of connection between two individuals. The simulation results show that the closeness p may have an active role in weakening both the spreading of epidemic and the vaccination. Besides, when vaccination is not allowed, the final recovered density increases with the value of the ratio of the infection rate to the recovery rate λ / μ . However, when vaccination is allowed the final density of recovered individual first increases and then decreases with the value of λ / μ . Two variables are designed to identify the relation between the individuals’ activities and their states. The results draw that both recovered and vaccinated frequency increase with the increase of the individuals’ activities. Meanwhile, the immune fee has less impact on the individuals’ vaccination than the closeness. While the λ / μ is in a certain range, with the increase of the value of λ / μ , the recovered frequency of the whole crowds reduces. Our results, therefore, reveal the fact that the best of intentions may lead to backfire.


docid: eqpxwwog

title: New biometric products flood out to tackle Covid-19

text: Contactless biometric systems aimed at combatting the Covid-19 virus are being launched at a significant rate – and adopted by high-profile users ranging from the United Nations to the Chinese police.


title: Atopie et infections

text: Summary There are obviously important and reciprocal relationships between atopy and infections. Atopy predisposes to infections of the target organ, i.e. the site of the allergic reaction. As allergic inflammation prepares the terrain for these infections, it is particularly important to fight against allergic inflammation by eliminating allergens and irritants from the atopic subject's environment. In some cases, topical anti-inflammatory drugs, such as cromoglycate or corticosteroids spray or ointment, must be used. Reciprocally, infections of the target organ accentuate atopic diseases by superimposing their specific inflammatory phenomena onto those of the allergic reaction, by amplifying this reaction and by creating hyperreactivity of the target organ. The possible role of Chlamydia pneumoniae infections in the pathogenesis of certain severe forms of chronic asthma could attribute a place to macrolides in the treatment or even the prophylaxis of asthma.


title: A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China

text: Abstract Background Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed. Methods We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020. Results Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients. Conclusions This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.