docid: bxqsqnaw

title: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort

text: BACKGROUND: Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. METHODS: Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’). A historical cohort of ‘classical’ KD served as a comparator. RESULTS: Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 11 cases (69%), while a further five cases had documented recent contact with a quantitative PCR-positive individual (31%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004). CONCLUSION: Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19. Trial registration number NCT02377245


title: Merit of an ursodeoxycholic acid clinical trial in COVID-19 patients

text: Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment”. Bear bile is rich in UDCA, comprising up to 40–50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration.


docid: tlxrvato

title: COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis

text: Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated D-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock who demonstrated immediate improvements in gas exchange and/or hemodynamics with systemic tPA.


title: Microbial contamination of drinking water and disease outcomes in developing regions

text: Drinking water is a major source of microbial pathogens in developing regions, although poor sanitation and food sources are integral to enteric pathogen exposure. Gastrointestinal disease outcomes are also more severe, due to under-nutrition and lack of intervention strategies in these regions. Poor water quality, sanitation and hygiene account for some 1.7 million deaths a year world-wide (3.1% of all deaths and 3.7% of all DALY’s), mainly through infectious diarrhoea. Nine out of 10 such deaths are in children and virtually all of the deaths are in developing countries. Major enteric pathogens in these children include: rotavirus, Campylobacter jejuni, enterotoxigenic Escherichia coli, Shigella spp. and Vibrio cholerae O1, and possibly enteropathogenic E. coli, Aeromonas spp. V. cholerae O139, enterotoxigenic Bacteroides fragilis, Clostridium difficile and Cryptosporidium parvum. All except the latter are easily control by chlorination of water, but recontamination of treated water is a huge problem. Emerging environmental pathogens, such as Helicobacter pylori and Burkholderia pseudomallei, may well be of significance in some regions. In adults, much less is understood of various sequellae such as myocarditis, diabetes, reactive arthritis and cancers some months–years after initial infections. So in addition to the traditional pathogens (helminths, Entamoeba histolytica, Giardia lamblia hepatitis A and E) various enteroviruses, C. jejuni and H. pylori are emerging issues in adults.


docid: mxfoouja

title: Factors influencing Dipylidium sp. infection in a free-ranging social carnivore, the spotted hyaena (Crocuta crocuta)()

text: We provide the first genetic sequence data for a Dipylidium species from a wild carnivore plus an analysis of the effects of ecological, demographic, physiological and behavioural factors on Dipylidium sp. infection prevalence in a social carnivore, the spotted hyaena (Crocuta crocuta), in the Serengeti National Park, Tanzania. Our sequence data from a mitochondrial gene fragment (1176 base pair long) had a similarity of between 99% and 89% to Dipylidium caninum. We determined infection prevalence in 146 faecal samples from 124 known animals in three social groups (termed clans) using molecular screening and Dipylidium proglottid presence. Our analysis revealed significantly higher infection prevalence in juveniles (55%) than adults (15.8%), indicating that predominantly juveniles maintained infection in clans. The likelihood of infection in juveniles significantly: (1) increased as the number of adults and older juveniles (>6 months) at communal dens increased, implying a positive relationship between this factor and the size of the intermediate host (probably a flea species) population at communal dens; (2) decreased as the number of younger juveniles (<6 months) increased, suggesting that the chance of susceptible juveniles ingesting infected fleas during self-grooming declined as the number of infected fleas per younger juvenile declined; and (3) decreased during periods of low prey abundance in clan territories when an increased reliance on long-distances foraging excursions reduces the number of clan members visiting communal dens, possibly resulting in a decline in flea populations at dens. Long-distance foraging also increases the intervals (in days) between nursing visits by lactating females to their offspring. Lengthy intervals between milk intake by infected juveniles may reduce adult Dipylidium fecundity and hence decrease infection prevalence in the den flea population. Our study provides useful insights into Dipylidium epidemiology in a social carnivore population subject to large fluctuations in prey abundance.


title: Interferons: Signaling, antiviral and viral evasion

text: Abstract Interferons (IFNs) were discovered as antiviral agents 50 years ago, and enormous progress has been made since then. Nowadays, IFNs (specifically type I IFNs), have been ascribed as the cytokines that bridge the innate and adaptive immunity soon after the recognition of pathogen-associated molecular patterns (PAMPs) by the infected host. Notably, a unifying mechanism for type I IFN production has been established upon innate immune detection. Thus, TLR 3, 4, 7 and 9 associate endosomal recognition of PAMPs to type I IFN responses, a mechanism that has been shown in plasmacytoid dendritic cells to be dependent on the PI3K/mTOR/S6K pathway. It is worth noting that pathogen recognition triggers a fine-tuned controlled program that not only includes the production of antiviral (IFN) and pro-inflammatory cytokines to initiate the antiviral response but also signals the cessation of the response through the induction of suppressors of cytokine signaling (SOCS). SOCS in turn is under tight regulation of the TAM receptors (protein tyrosine kinase receptors TYRO3, AXL and MER), and activation of which thereby protects the host from the threats of autoimmune diseases.


title: COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities

text: Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients.


title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

text: Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.


title: Membranous glomerulonephritis in the Iberian lynx (Lynx pardinus)

text: Abstract The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy (n =8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.


title: Emergence and re-emergence of viral diseases of the central nervous system

text: Neurologic disease is a major cause of disability in resource-poor countries and a substantial portion of this disease is due to infections of the CNS. A wide variety of emerging and re-emerging viruses contribute to this disease burden. New emerging infections are commonly due to RNA viruses that have expanded their geographic range, spread from animal reservoirs or acquired new neurovirulence properties. Mosquito-borne viruses with expanding ranges include West Nile virus, Japanese encephalitis virus and Chikungunya virus. Zoonotic viruses that have recently crossed into humans to cause neurologic disease include the bat henipaviruses Nipah and Hendra, as well as the primate-derived human immunodeficiency virus. Viruses adapt to new hosts, or to cause more severe disease, by changing their genomes through reassortment (e.g. influenza virus), mutation (essentially all RNA viruses) and recombination (e.g. vaccine strains of poliovirus). Viruses that appear to have recently become more neurovirulent include West Nile virus, enterovirus 71 and possibly Chikungunya virus. In addition to these newer challenges, rabies, polio and measles all remain important causes of neurologic disease despite good vaccines and global efforts toward control. Control of human rabies depends on elimination of rabies in domestic dogs through regular vaccination. Poliovirus eradication is challenged by the ability of the live attenuated vaccine strains to revert to virulence during the prolonged period of gastrointestinal replication. Measles elimination depends on delivery of two doses of live virus vaccine to a high enough proportion of the population to maintain herd immunity for this highly infectious virus.


title: Directions for Disaster Nursing Education in the United States

text: Because of their diverse education, experience, and practice settings, nurses are uniquely qualified to be first receivers, care givers, and leaders in any large-scale public health emergency. Many nurses, however, continue to feel inadequately prepared to function effectively in these types of situations. Great strides have been made since 2001, but much work remains to be accomplished. This article focuses on newer approaches used to teach nurses the principles of disaster preparedness. It also addresses the need to incorporate mass casualty care and disaster management skills into undergraduate curricula, continuing nurse education, and advanced degree programs for nurses in the United States.


title: A Fully Integrated Paper-Microfluidic Electrochemical Device for Simultaneous Analysis of Physiologic Blood Ions

text: A fully integrated paper microfluidic electrochemical device equipped with three different cation permeable films is developed to determine blood ions (Cl(−), Na(+), K(+), and Ca(2+)) at a time. These blood ions that are normally dissolved in the real human blood stream are essential for cell metabolisms and homeostasis in the human body. Abnormal concentration of blood ions causes many serious disorders. The optimized microfluidic device working without any external power source can directly and effectively separate human blood components, and subsequently detect a specific blood ion with minimized interference. The measured sensitivity to Cl(−), K(+), Na(+), and Ca(2+) are −47.71, 45.97, 51.06, and 19.46 in mV decade(−1), respectively. Potentiometric responses of the microfluidic devices to blood serum samples are in the normal ranges of each cation, and comparable with responses from the commercial blood ion analyzer Abbott i-Stat.


title: Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

text: We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing “trained” nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a “low-risk–high-reward” preventive measure in saving lives during this unprecedented COVID-19 pandemic.


title: Celastrol inhibits dengue virus replication via up-regulating type I interferon and downstream interferon-stimulated responses

text: Abstract Ethnopharmacological relevance and aim of the study Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported. This work aimed to investigate the anti-DENV effect and possible mechanism of celastrol in vitro and in vivo. Methods A four-serotype DENV infection system was performed to determine the anti-DENV effect of celastrol by detecting DENV RNA replication and protein synthesis. The precise anti-DENV replication mechanism of celastrol was clarified using specific RNA silencing and specific inhibitor. In addition, the therapeutic efficacy of celastrol was evaluated by monitoring survival rates and clinical scores in a DENV-infected Institute of Cancer Research (ICR) suckling mouse model. Results Celastrol inhibited DENV-1, -2, -3, and -4 RNA replication with EC50 values of 0.19 ± 0.09, 0.12 ± 0.11, 0.16 ± 0.14, and 0.17 ± 0.08 μM, respectively. This antiviral effect of celastrol was associated with celastrol-induced interferon-α (IFN-α) expression and was attenuated by a specific inhibitor of the JAK–STAT signaling pathway downstream of IFN-α or specific shRNA. Furthermore, celastrol protected ICR suckling mice against life-threatening DENV infection. Conclusion Celastrol represents a potential anti-DENV agent that induces IFN-α expression and stimulates a downstream antiviral response, making the therapy a promising drug or dietary supplement for the treatment of DENV-infected patients.


title: Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19

text: Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner's factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a “do not intubate” order.


title: Analysis of synonymous codon usage patterns in sixty-four different bivalve species

text: Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates.


title: Perspective: The one-health way

text: The health of animals, humans and the environment will be better served by breaking down barriers, says Laura H. Kahn.


title: Comparison of three commercial RT-PCR systems for the detection of respiratory viruses

text: Abstract Background Due to the insensitivity of rapid tests for respiratory viruses, nucleic acid amplification tests are quickly becoming the standard of care. Objectives and study design The performance of the FilmArray Respiratory Panel (RP) and Verigene RV+ (RV+) were compared in a retrospective analysis of 89 clinical specimens previously determined to be positive for the following viruses by our test of record, Prodesse (Pro): influenza A (29, FluA), influenza B (13, FluB), respiratory syncytial virus (12, RSV), human metapneumovirus (10, hMPV), parainfluenza (14, PIV), and adenovirus (10, AdV). Samples positive for influenza A, B or RSV were tested by both methods, while the remainder were tested by RP only. True positives were defined as positive by two or more assays. Results Limit of detection (LOD) analyses demonstrated Pro had the lowest LOD for all FluA strains tested, PIV1, PIV2 and AdV; RV+ had the lowest LOD for FluB; and RP had the lowest LOD for RSV, PIV3 and hMPV. Of the 55 samples tested by RV+, all 54 true positive samples were positive by RV+. Of the 89 samples tested by RP, 85 of the 88 true positive samples were positive by RP. From these results, the overall sensitivities for influenza A, B and RSV were 100% and 98% for RV+ and RP, respectively. The overall sensitivity of RP for all viruses was 97%. Conclusions In summary, these systems demonstrated excellent performance. Furthermore, each system has benefits which will ensure they will all have a niche in a clinical laboratory.


title: Part I. SARS-CoV-2 triggered ‘PANIC’ attack in severe COVID-19()

text: The COVID-19 pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constraining our freedom of movement. This respiratory tract infection is unprecedented in that it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the reaction is a productive and mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a virus capable of producing what can only be described as a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, that then leads to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the SARS-CoV-2 virus' ability to trigger what we now designate for the first time, as a ‘Prolific Activation of a Network-Immune-Inflammatory Crisis’, or ‘PANIC’ Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing ‘PANIC’; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.


title: X‐ray crystallographic determination of the structure of the influenza C virus haemagglutinin‐esterase‐fusion glycoprotein

text: The structure of the haemagglutinin‐esterase‐fusion (HEF) glycoprotein from influenza C virus has been determined to 3.2 Å resolution by X‐ray crystallography. A synthetic mercury‐containing esterase inhibitor and receptor analogue, 9‐acetamidosialic acid α‐thiomethylmercuryglycoside, was designed as the single isomorphous heavy‐atom derivative. The asymmetric unit of one crystal form (form I; P4(3)22, a = b = 155.4, c = 414.4 Å) contained an HEF trimer. Six mercury sites identifying the three haemagglutination and three esterase sites were located by difference Patterson map analysis of a 6.5 Å resolution derivative data set. These positions defined the molecular threefold‐symmetry axis of the HEF trimer. A molecular envelope was defined by averaging a 7.0 Å resolution electron‐density map, phased by single isomorphous replacement (SIR), about the non‐crystallographic threefold‐symmetry axis. Iterative non‐crystallographic symmetry averaging in real space, solvent flattening and histogram matching were used to extend the phases to 3.5 Å resolution. Molecular replacement of the model into a second crystal form (form II; P4(3)2(1)2, a = b = 217.4, c = 421.4 Å) containing two HEF trimers per asymmetric unit permitted iterative ninefold averaging of the electron density. The 3.5 Å electron‐density map allowed an unambiguous tracing of the polypeptide chain and identification of N‐linked carbohydrates. The model has been refined by least squares to 3.2 Å resolution (R (free) = 26.7%).


title: Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

text: Abstract The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is an essential component of the replication/transcription complex. It comprises various domains, the organization of which differs between CoV genera, due to duplication or absence of some domains. However, eight domains of Nsp3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called “hypervariable region”), a macrodomain (also named “X domain”), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro), the Nsp3 ectodomain (3Ecto, also called “zinc-finger domain”), as well as the domains Y1 and CoV-Y of unknown functions. In addition, the two transmembrane regions, TM1 and TM2, exist in all CoVs. The three-dimensional structures of domains in the N-terminal two thirds of Nsp3 have been investigated by X-ray crystallography and/or nuclear magnetic resonance (NMR) spectroscopy since the outbreaks of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003 as well as Middle-East Respiratory Syndrome coronavirus (MERS-CoV) in 2012. In this review, the structures and functions of these domains of Nsp3 are discussed in depth.


title: Molecular characterization of whole genome sequence of infectious bronchitis virus 624I genotype confirms the close relationship with Q1 genotype

text: Infectious Bronchitis virus (IBV) genotype Q1 was detected for the first time in China in 1996, and then spread worldwide. The first report of Q1 genotype in Italy occurred in 2011 and a deep molecular investigation of a Q1 isolated in Italy in 2013 has led to speculation regarding the origin of this genotype. Phylogenetic analysis of the S1 sequence of a Q1 Italian strain revealed a close relationship with sequences of the 624I strains circulating in Italy in the early 1990s and this led to the idea that 624I was an ancestor of the Q1 genotype. Despite the fact that most heterogeneity of IBVs occurs in the S1 gene, the sequence analysis of this gene alone was not sufficient to confirm or deny this hypothesis. In the present study, an Italian 624I (gammaCoV/AvCov/Ck/Italy/IP14425/96) was fully sequenced for the first time and compared to all available complete Q1 genome sequences. This analysis confirmed the genetic correlation between GammaCoV/AvCov/Ck/Italy/IP14425/96 and Q1 strains, suggesting a common origin between 624I and Q1 genotypes.


Phylogeny and expression of the tetraspanin CD9 in salmonid cell lines in response to interferon stimulation


title: Impact of Cerebrovascular and Cardiovascular Diseases on Mortality and Severity of COVID-19 – Systematic Review, Meta-analysis, and Meta-regression

text: Background We conducted this systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, cardiovascular disease, and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. Results A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with increased poor composite outcome (RR 2.04 [1.43, 2.91], p<0.001; I(2): 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92, 2.96], p<0.001; I(2): 0%) and was borderline significant for severe COVID-19 (RR 1.88 [1.00, 3.51], p=0.05; I(2): 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71, 2.91], p<0.001; I(2): 60%), and its mortality (RR 2.25 [1.53, 3.29], p<0.001; I(2): 33%) and severe COVID-19 (RR 2.25 [1.51, 3.36], p<0.001; I(2): 76%) subgroup. Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. The association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. Conclusion Cerebrovascular and cardiovascular diseases were associated with increased risk for poor outcome in COVID-19.


docid: vknxzzgm

title: Delayed‐Phase Thrombocytopenia in Patients of Coronavirus Disease 2019 (COVID‐19)

text: COVID‐19 can affect the hematopoietic system. Thrombocytopenia at admission was prevalent, while late‐phase or delayed‐phase thrombocytopenia (occurred 14 days after symptom onset) is obscure. This retrospective single‐center study screened 450 COVID‐19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25th to March 9th, 2020. COVID‐19 associated delayed‐phase thrombocytopenia occurred in 11.8% percent of enrolling patients. The delayed‐phase thrombocytopenia in COVID‐19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed‐phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed‐phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also presented bone marrow aspiration pathology of three patients with delayed‐phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune mediated platelet destruction might account for the delayed‐phase thrombocytopenia in a group of patients. Besides, clinicians need to pay attention to the delayed‐phase thrombocytopenia especially at 3‐4 weeks after symptom onset.


title: Internationally lost COVID-19 cases

text: Abstract Background With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO). While many countries have implemented flight restrictions to China, an increasing number of cases with or without travel background to China are confirmed daily. These developments support concerns on possible unidentified and unreported international COVID-19 cases, which could lead to new local disease epicenters. Methods We have analyzed all available data on the development of international COVID-19 cases from January 20th, 2020 until February 18th, 2020. COVID-19 cases with and without travel history to China were divided into cohorts according to the Healthcare Access and Quality Index (HAQ-Index) of each country. Chi-square and Post-hoc testing were performed. Results While COVID-19 cases with travel history to China seem to peak for each HAQ-cohort, the number of non-travel related COVID-19 cases seem to continuously increase in the HAQ-cohort of countries with higher medical standards. Further analyses demonstrate a significantly lower proportion of reported COVID-19 cases without travel history to China in countries with lower HAQ (HAQ I vs. HAQ II, posthoc p < 0.01). Conclusions Our data indicate that countries with lower HAQ-index may either underreport COVID-19 cases or are unable to adequately detect them. Although our data may be incomplete and must be interpreted with caution, inconsistencies in reporting COVID-19 cases is a serious problem which might sabotage efforts to contain the virus.


title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1

text: BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. METHODS AND FINDINGS: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). CONCLUSION: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission.


title: Sensitivity and specificity of the user-seal-check in determining the fit of N95 respirators

text: Summary N95 respirators are recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to prevent the inhalation of droplets which may transmit respiratory pathogens. The reliability of N95 respirators in preventing transmission depends on their fit to the wearer. Quantitative fit testing (QNFT) is the gold standard used to determine this fit objectively. The manufacturers of the respirators also recommend performing a self-reported user-seal-check to detect for leakage. This study aims to investigate the capability of the user-seal-check in determining the fit of N95 respirators by investigating the sensitivity and specificity of the user-seal-check compared with QNFT. A prospective and cross-sectional research design was used. A total of 204 local Chinese undergraduate nursing students were recruited to test two commonly used respirator models (3M 1860S and 3M 1862). The results of the user-seal-check were compared with the results of the gold standard QNFT using the Condensation Nucleus Counter Fit Tester System. The sensitivity and specificity of the user-seal-check results obtained with the respirators were calculated. The results indicated low sensitivity, accuracy and predictive value of the user-seal-check in determining the fit of the N95 respirators. The user-seal-check was not found to be reliable as a substitute for QNFT. The results also suggested that the user-seal-check may be unreliable for detecting gross leakage. We recommend that QNFT is used to determine the fit of N95 respirators.


title: Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial Cells and Their Effect on Antiviral Immunity

text: The scientific community has reported several cases of microbes that exhibit elevated rates of antibiotic resistance in different regions of the planet. Due to this emergence of antimicrobial resistant microorganisms, the use of antibiotics as promoters of livestock animals’ growth is being banned in most countries around the world. One of the challenges of agricultural immunology therefore is to find alternatives by modulating the immune system of animals in drug-independent safe food production systems. In this regard, in an effort to supplant antibiotics from bovine feeds, several alternatives were proposed including the use of immunomodulatory probiotics (immunobiotics). The purpose of this review is to provide an update of the status of the modulation of intestinal antiviral innate immunity of the bovine host by immunobiotics, and the beneficial impact of immunobiotics on viral infections, focused on intestinal epithelial cells (IECs). The results of our group, which demonstrate the capacity of immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered immune responses in bovine IECs and improve the resistance to viral infections, are highlighted. This review provides comprehensive information on the innate immune response of bovine IECs against virus, which can be further investigated for the development of strategies aimed to improve defenses in the bovine host.


title: Modulation of Stop Codon Read-Through Efficiency and Its Effect on the Replication of Murine Leukemia Virus

text: Translational readthrough—suppression of termination at a stop codon—is exploited in the replication cycles of several viruses and represents a potential target for antiviral intervention. In the gammaretroviruses, typified by Moloney murine leukemia virus (MuLV), gag and pol are in the same reading frame, separated by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-Pol fusion protein. Here, we investigated the effect on MuLV replication of modulating readthrough efficiency. We began by manipulating the readthrough signal in the context of an infectious viral clone to generate a series of MuLV variants in which readthrough was stimulated or reduced. In carefully controlled infectivity assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defect and that a 10-fold reduction essentially abolished replication. However, up to an ∼8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus. These high levels of readthrough were achieved using a two-plasmid system, with Gag and Gag-Pol expressed from separate infectious clones. We also modulated readthrough by silencing expression of eukaryotic release factors 1 and 3 (eRF1 and eRF3) or by introducing aminoglycosides into the cells. The data obtained indicate that gammaretroviruses tolerate a substantial excess of viral Gag-Pol synthesis but are very sensitive to a reduction in levels of this polyprotein. Thus, as is also the case for ribosomal frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the most beneficial. IMPORTANCE Many pathogenic RNA viruses and retroviruses use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase enzymes. These translational “recoding” processes are potential targets for antiviral intervention, but we have only a limited understanding of the consequences to virus replication of modulating the efficiency of recoding, particularly for those viruses employing readthrough. In this paper, we describe the first systematic analysis of the effect of increasing or decreasing readthrough efficiency on virus replication using the gammaretrovirus MuLV as a model system. We find unexpectedly that MuLV replication is only slightly inhibited by substantial increases in readthrough frequency, but as with other viruses that use recoding strategies, replication is quite sensitive to even modest reductions. These studies provide insights into both the readthrough process and MuLV replication and have implications for the selection of antivirals against gammaretroviruses.


docid: yzyixucr

title: Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan

text: Abstract Objective COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate current status of COVID-19 in Taiwan and analyze the source of infection. Methods National data regarding SARS-CoV-2 infection were obtained from Taiwan CDC at the end of April, 2020. These data were subjected for analysis of the current status and correlation between indigenous and imported COVID-19 cases. Phylogenetic tree was performed to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates. Results The initial case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most of cases were identified as imported (79.9%; 343/429) with majority transmitted from United States of America (22.1%) and United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%). Conclusion This study suggests that importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.


title: A system dynamics approach to understanding the One Health concept

text: There have been many terms used to describe the One Health concept, including movement, strategy, framework, agenda, approach, among others. However, the inter-relationships of the disciplines engaged in the One Health concept have not been well described. To identify and better elucidate the internal feedback mechanisms of One Health, we employed a system dynamics approach. First, a systematic literature review was conducted via searches in PubMed, Web of Knowledge, and ProQuest with the search terms: ‘One Health’ and (concept* or approach*). In addition, we used the HistCite(®) tool to add significant articles on One Health to the library. Then, of the 2368 articles identified, 19 were selected for evaluating the inter-relationships of disciplines engaged in One Health. Herein, we report a visually rich, theoretical model regarding interactions of various disciplines and complex problem descriptors engaged in One Health problem solving. This report provides a conceptual framework for future descriptions of the interdisciplinary engagements involved in One Health.


title: Severe Pneumonia Caused by Legionella pneumophila Differential Diagnosis and Therapeutic Considerations

text: Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L pneumophila pneumonia from other respiratory pathogens. L pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space.


title: Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014

text: BACKGROUND: We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh. METHODS: Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals. RESULTS: We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively. CONCLUSION: Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh.


e‐Mental Health Options in the COVID‐19 Pandemic and Beyond


title: 15 Governance, human rights and infectious disease: theoretical, empirical and practical perspectives

text: Publisher Summary This chapter explores the fundamental obligation of governments to protect health. This obligation extends not only to the provision of health care or to the control of infectious disease outbreaks, but also to the cessation of human rights violations that contribute to poor health or disease risk. The relationship between the health status of a population and the behavior of the government under which that population lives is important during war or civil crisis settings, and in the context of chronic health issues such as nutrition, famine, and child mortality. As measured by indicators such as accountability, stability, rule of law, respect for human rights, and the existence of an independent civil society, plays a significant role in health outcomes—a role independent of, and perhaps even superior to, host genetics, insect vectors, or individual behaviors. Famines stem not solely from bad weather or genetics, but also from the failure of governments to protect their populations from civil strife, or to equitably distribute food aid. Despite the widespread acceptance of these findings, the influence of governance on infectious disease spread has received far less attention. Both governance and health can be measured in many different ways, and one factor complicating efforts to measure the association between the two is the difficulty finding accurate, sensitive, and specific enough indicators for either variable. Broad measures of population health—such as life expectancy, and infant and maternal mortality—have been chosen by a number of authors, in part because these indicators capture multiple specific diseases and are broadly distributed across the population.


SARS-CoV-2 antibody screening in healthcare workers in a tertiary centre in North West England


title: Viral respiratory infections in the community: Epidemiology, agents, and interventions

text: Viral respiratory infections are a leading cause of acute morbidity in the community. The annual frequency of respiratory illness rises during the second year of life, falls during subsequent years, increases again during child-bearing years, then decreases with advancing age (although some increase may be seen in the elderly). In terms of restriction on activity and prompting of visits to physicians, the greatest number of illnesses are associated with rhinoviruses followed by influenza viruses. However, comparing rhinovirus and influenza, there is no doubt that influenza viruses produce more severe symptoms. In some years, when there is a major influenza outbreak, they may even be identified at greater frequency. Moreover, unlike with other viruses, severity of influenza infection is high at all ages, but especially in older individuals. Influenza vaccine, which has been available for half a century, has proved effective in preventing hospitalizations for pneumonia and influenza during outbreaks of influenza types A and B. The antiviral agents amantadine and rimantadine provide approximately equivalent, and significant, efficacy in protection against clinical illness resulting from influenza type A only. However, the potential for side effects is more marked with amantadine. Some studies have shown that the rate of treatment withdrawal is no greater with rimantadine than with placebo. As we enter the next century, we may well see improvements in influenza vaccines, as well as the advent of antiviral agents that are effective against both type A and type B influenza.


title: The Role of the Intestinal Microbiota in the Pathogenesis of Necrotizing Enterocolitis

text: Development of necrotizing enterocolitis (NEC) requires a susceptible host, typically a premature infant or an infant with congenital heart disease, enteral feedings and bacterial colonization. Although there is little doubt that microbes are critically involved in the pathogenesis of NEC, the identity of specific causative pathogens remains elusive. Unlike established normal adult gut microbiota, which is quite complex, uniform, and stable, early postnatal bacterial populations are simple, diverse, and fluid. These properties complicate studies aimed at elucidating characteristics of the gut microbiome that may play a role in the pathogenesis of NEC. A broad variety of bacterial, viral, and fungal species have been implicated in both clinical and experimental NEC. Frequently, however, the same species have also been found in physiologically matched healthy individuals. Clustered outbreaks of NEC, in which the same strain of a suspected pathogen is detected in several patients suggest, but do not prove, a causative relationship between the specific pathogen and the disease. Studies in Cronobacter sakazakii, the best characterized NEC pathogen, have demonstrated that virulence is not a property of a bacterial species as a whole, but rather a characteristic of certain strains, which may explain why the same species can be pathogenic or non-pathogenic. The fact that a given microbe may be innocuous in a full-term, yet pathogenic in a pre-term infant has led to the idea of opportunistic pathogens in NEC. Progress in understanding the infectious nature of NEC may require identifying specific pathogenic strains and unambiguously establishing their virulence in animal models.


title: Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies

text: The present work is an investigation to test hydroxychloroquine as an inhibitor for the COVID-19 main protease. Molecular docking studies revealed a high docking score and interaction energies and decent level of docking within the cavity in protease moiety. Molecular dynamics simulations also lead to the evaluation of conformational energies, average H-bonding distance, RMSD plots etc. Large RMSD fluctuations for the first 2 ns seem to provide the conformational and rotational changes associated with the drug molecule when it comes into the vicinity on the protease matrix. Snapshots of structural changes with respect to time vividly indicates that drug molecule has a profound impact on the binding sites as well as overall geometry of the protease moiety. On the whole, hydroxyxhloroquine confers good inhibitory response to COVID-19 main protease. We hope the present study should help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus.


The American College of Surgeons Responds to COVID-19


Preliminary recommendations for lung surgery during COVID‐19 epidemic period


title: Saffold virus infection associated with human myocarditis

text: Abstract Background Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been isolated from different anatomical compartments, including the myocardium, but, until now, it has not been possible to demonstrate the accompanying histopathological signs of inflammation. Objectives The aim of the study was to examine if saffold virus is capable of causing invasive infection in the human myocardium. Study design Using real-time PCR, we retrospectively examined formalin-fixed paraffin embedded cardiac tissue specimens from 150 deceased individuals diagnosed with myocarditis at autopsy. The results were compared with histological findings. Results and conclusions Saffold virus was detected in the myocardium, lung tissue and blood of one child and was accompanied by histopathological inflammation in the heart and lungs, which was supportive of a viral infection. These findings suggest that cardioviruses may be associated with myocarditis in humans.


title: European SMEs amidst the COVID-19 crisis: assessing impact and policy responses

text: We consider how the COVID-19 pandemic has challenged European small- and medium-sized enterprises (SMEs) in the manufacturing sector, and draw suggests policy implications. The sudden onslaught of the pandemic has acted as an economic shock, and we consider how it is likely to affect different types of manufacturing SMEs. We distinguish between immediate effects, a result of the almost-simultaneous lockdowns across Europe and its major trading partners, and longer-term implications for both SMEs and the global value chains where they are inserted. In the shorter run, most SMEs have faced logistical challenges in addition to demand disruptions, although the severity has differed across firms and industries. We argue that in the longer-term, there will be different challenges and opportunities depending on the type of SME. Policy interventions will also need to be sensitive to the different types of SMEs, rather than adopting a one-size-fits-all approach. The policy mix will need to shift from its initial focus on the survival of European SMEs in the short term, towards a more structural and longer-term approach based on promoting their renewal and growth through innovation, internationalization and networking.


title: Cryptosporidium-associated diarrhoea in neonatal calves in Algeria

text: Abstract Neonatal calf diarrhoea triggered by the enteric protozoan parasite Cryptosporidium is a leading cause of morbidity and mortality in calves aged 1-month-old or younger globally. Infected cattle in general and calves in particular have also been demonstrated as major contributors of zoonotic C. parvum oocysts in the environment and have been linked to a number of waterborne outbreaks of human cryptosporidiosis. Little is known on the occurrence, geographical distribution, and molecular diversity of Cryptosporidium infections affecting bovine populations in Algeria. In this study faecal specimens were randomly collected from 460 cattle aged between two days and 18 months on 10 farms located in the provinces of Aïn Defla, Blida, Sétif, and Tizi Ouzou between the autumn of 2015 and the spring of 2016. Faecal samples were microscopically examined using the modified Ziehl-Neelsen acid-fast technique as screening method. Microscopy-positive samples were confirmed by a commercial coproantigen enzyme-linked immunosorbent assay (Bio-X Diagnostics). The identification of Cryptosporidium species and sub-genotypes in confirmed samples was conducted by PCR and sequence analyses of the small subunit ribosomal RNA (ssu rRNA) and the 60 kDa glycoprotein (gp60) genes of the parasite. Overall, 52.2% (240/460) of the investigated cattle tested positive to Cryptosporidium by microscopy. The infection was widespread in all 10 farms surveyed, but was significantly more prevalent in those from Blida in the central part of the country. Bovine cryptosporidiosis affected cattle of all age groups but with different outcomes. Pre-weaned (up to one month old) calves typically presented with diarrhoea, whereas older animals mostly harboured sub-clinical infections. The commercial ELISA used only detected 15.8% (38/240) of the samples that previously tested positive by microscopy, demonstrating a poor performance in field epidemiological surveys. Sequence analysis of the 29 isolates generated at the ssu rRNA loci confirmed the presence of four Cryptosporidium species including C. parvum (72.4%), C. bovis (13.8%), C. andersoni, (3.4%), and C. ryanae (3.4%). Two additional isolates (7.0%) could only be identified at the genus level. Eight out of the 21 isolates assigned to C. parvum were identified as sub-genotype IIaA16G2R1 at the gp60 locus. C. parvum was almost exclusively found infecting pre-weaned calves, whereas C. ryanae and C. andersoni were only detected in asymptomatic animals. Bovine cryptosporidiosis is highly endemic in the surveyed area and represents a veterinary public health concern that should be adequately tackled by Algerian veterinary health authorities and policy makers.


title: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity

text: The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.


title: Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19

text: Abstract Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.


title: Orbitofrontal involvement in a neuroCOVID‐19 patient

text: Neurological manifestations of COVID‐19 such as encephalitis and seizures have been increasingly reported, but our understanding of COVID‐related brain injury is still limited. Herein we describe prefrontal involvement in a COVID‐19 patient who presented prior anosmia, raising the question of a potential trans‐olfactory‐bulb brain invasion.


title: Diverse roles of host RNA-binding proteins in RNA virus replication

text: Plus-strand (+)RNA viruses co-opt host RNA-binding proteins (RBPs) to perform many functions during viral replication. A few host RBPs have been identified that affect the recruitment of viral (+)RNAs for replication. Other subverted host RBPs help the assembly of the membrane-bound replicase complexes, regulate the activity of the replicase and control minus- or plus-strand RNA synthesis. Host RBPs also affect the stability of viral RNAs, which have to escape cellular RNA degradation pathways. While many host RBPs seem to have specialized functions, others participate in multiple events during infection. Several conserved RBPs, such as eEF1A, hnRNP proteins and the Lsm 1–7 complex, are co-opted by evolutionarily diverse (+)RNA viruses, underscoring some common themes in virus-host interactions. On the other hand, viruses also hijack unique RBPs, suggesting that (+)RNA viruses could utilize different RBPs to perform similar functions. Moreover, different (+) RNA viruses have adapted distinctive strategies for co-opting unique RBPs. Altogether, a deeper understanding of the functions of the host RBPs subverted for viral replication will help development of novel antiviral strategies and give new insights into host RNA biology.


Some unanswered questions about vaccination


title: 10 Biodiversity and Health Scenarios

text: Abstract: In “An Essay on the Principle of Population” (1798), Thomas Malthus established one of the first scenarios that linked natural constraints (agricultural production) with demography and economic growth. This essay was an essential contribution not only to the development of economic theories but also to ecological and evolutionary theories with the concept of a limiting capacity within a given environment. The Malthusian view of human demography is at the core of the book by Ehrlich and Ehrlich “The Population Bomb”, which called for active control of births in order to avoid famine, resource depletion and corporate collapse.


title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

text: BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention.


title: Local delivery of siRNA-loaded calcium phosphate nanoparticles abates pulmonary inflammation

text: Abstract The local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach to dampen inflammation during pulmonary diseases. For the local therapeutic treatment of pulmonary inflammation, we produced multi-shell nanoparticles consisting of a calcium phosphate core, coated with siRNAs directed against pro-inflammatory mediators, encapsulated into poly(lactic-co-glycolic acid), and coated with a final outer layer of polyethylenimine. Nasal instillation of nanoparticles loaded with a mixture of siRNAs directed against different cytokines to mice suffering from TH1 cell-mediated lung inflammation, or of siRNA directed against NS-1 in an influenza infection model led to a significant reduction of target gene expression which was accompanied by distinct amelioration of lung inflammation in both models. Thus, this study provides strong evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of inflammatory disorders of the lung.


COVID-19, type 1 diabetes, and technology: why paediatric patients are leading the way


Guest Editorial: SARS – future considerations for nurses


title: Right Ventricular Clot in Transit in COVID-19: Implications for the Pulmonary Embolism Response Team

text: Abstract Severe acute respiratory syndrome coronavirus 2 is associated with a prothrombotic state in infected patients. After presenting a case of right ventricular thrombus in a COVID-19 patient, we discuss the unique challenges in the workup and treatment of COVID-19 patients highlighting our COVID-19 modified pulmonary embolism response team (PERT) algorithm.


title: Avian coronavirus infectious bronchitis virus susceptibility to botanical oleoresins and essential oils in vitro and in vivo

text: Abstract Anti-coronaviral activity of a mixture of oleoresins and essential oils from botanicals, designated QR448(a), was examined in vitro and in vivo. Treatment of avian infectious bronchitis virus (IBV) with QR448(a) reduced the virus titer as measured in two laboratory host systems, Vero E6 cells and embryonating eggs. The effect of QR448(a) on IBV in chickens was also investigated. Administering QR448(a) to chickens at a 1:20 dilution by spray, 2h before challenge with IBV was determined to be the most effective treatment. Treatment decreased the severity of clinical signs and lesions in the birds, and lowered the amount of viral RNA in the trachea. Treatment with QR448(a) protected chickens for up to 4 days post-treatment from clinical signs of disease (but not from infection) and decreased transmission of IBV over a 14-day period. Anti-IBV activity of QR448(a) was greater prior to virus attachment and entry indicating that the effect is virucidal. In addition, QR448(a) had activity against both Massachusetts and Arkansas type IB viruses, indicating that it can be expected to be effective against IBV regardless of serotype. To our knowledge, this is the first report on the in vivo use of a virucidal mixture of compounds effective against the coronavirus IBV.


Wresting SARS from Uncertainty


title: DANGER IN DANGER: INTERPERSONAL VIOLENCE DURING COVID-19 QUARANTINE

text: Abstract Background Intimate partner violence (IPV) is defined as physical or sexual violence, emotional abuse and stalking. It is typically experienced by women but can also be experienced by men. During quarantine due to the COVID-19, home risks to become a very dangerous place for victims of domestic violence. Method Very recent studies focusing on abusive situations during COVID emergence were identified in PubMed/Medline, Scopus, Embase. Results During the COVID-19 outbreak people have encountered an invisible and dark enemy and an experience of impotence. Due to the feelings of frustration and agitation, aggression arises with possible transgenerational transmission of trauma and violence. Conclusions Especially during quarantine and COVID emergence around the world there is a need of programs aimed to prevent acts of domestic violence and to achieve accurate assessment of multiple domains of abuse (psychological, physical, sexual) provided by trained multidisciplinary staffs (including psychiatrists, psychologists, social and legal services).


title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China

text: BACKGROUND: The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small–medium cities and rural areas. OBJECTIVES: To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. METHODS: Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 2025 children enrolled in the study, 971 (48·0%) were positive for at least one viral pathogen, in which 890 (91·7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35·8%), respiratory syncytial virus (RSV; 30·5%) and human rhinovirus (HRV; 21·5%). Co-infections were found in 302 cases (31·1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. CONCLUSIONS: This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong.


title: Animal modeling in bone research—Should we follow the White Rabbit?

text: Animal models are live subjects applied to translational research. They provide insights into human diseases and enhance biomedical knowledge. Livestock production has favored the pace of human social development over millennia. Today's society is more aware of animal welfare than past generations. The general public has marked objections to animal research and many species are falling into disuse. The search for an ideal methodology to replace animal use is on, but animal modeling still holds great importance to human health. Bone research, in particular, has unmet requirements that in vitro technologies cannot yet fully address. In that sense, standardizing novel models remains necessary and rabbits are gaining in popularity as potential bone models. Our aim here is to provide a broad overview of animal modeling and its ethical implications, followed by a narrower focus on bone research and the role rabbits are playing in the current scenario.


title: Estimating the serial interval of the novel coronavirus disease (COVID‐19) based on the public surveillance data in Shenzhen, China from January 19 to February 22, 2020

text: BACKGROUNDS: The novel coronavirus disease (COVID‐19) poses serious threat to global public health and economics. Serial interval (SI), time between the symptom onsets of a primary case and a second case, is a key epidemiological parameter. We estimated SI of COVID‐19 in Shenzhen, China based on 27 records of transmission chains. METHODS: We adopted three parametric models: Weibull, Lognormal and Gamma distributions and an interval censored likelihood framework. The three models were compared using the corrected Akaike information criterion (AICc). We also fitted the epidemic curve of COVID‐19 to the exponential growth to estimate the reproduction number. FINDINGS: Using a Weibull distribution, we estimated mean SI at 5.9 days (95%CI: 3.9−9.6) and a standard deviation (SD) at 4.8 days (95%CI: 3.1−10.1). Using a logistic growth model, we estimated the basic reproduction number in Shenzhen at 2.6 (95%CI: 2.4−2.8). CONCLUSION: The SI of COVID‐19 is relative shorter than that of SARS and MERS, other two beta coronavirus diseases, which suggests the iteration of the transmission was rapid. It is crucial to isolate close contacts promptly to control the spread of COVID‐19 effectively.


title: Purification and biophysical properties of human coronavirus 229E

text: Abstract Coronavirus 229E was grown to high titers in diploid fibroblast cells under medium containing twice the normal concentrations of amino acids and vitamins. Growth curves showed maximum virus production at multiplicities of infection of 0.1 and 1; maximum titers of intracellular virus occurred at 22–24 hr and of extracellular virus at 26 hr postadsorption. Tube infectivity titers ranged from 109.0–109.5 TCID50/ml and plaque titers from 1010.2–1010.9 y PFU/ml at the time of peak virus production, when no cytopathology was evident. Virus titer dropped rapidly between 26 and 56 hr, coincident with increasing cytopathology. A single precipitin band was observed in immunodiffusion and immunoelectrophoresis between concentrated virus preparations and antiserum to purified 229E. Neuraminidase and hemagglutinin assays were negative. Virus was purified by two procedures: adsorption to and elution from human “0” erythrocytes and CaHPO4 gel followed by equilibrium sucrose gradient centrifugation, and PEG precipitation followed by equilibrium glycerol/tartrate gradients and rate zonal sucrose or glycerol/tartrate gradients. Final lots of purified virus containing <0.02% of the crude tissue culture proteins had absorption maxima at 256 nm and minima at 241.2 nm and a mean extinction coefficient of E 1cm 1% = 54.3 at 256 nm. The fully corrected sedimentation coefficient for the intact virion was S 20,v 0 = 381 S. PAGE by different techniques revealed seven polypeptides of mean apparent molecular weights between 16,900 and 196,100. Six contained carbohydrate and one contained lipid. Electropherograms of 3H- and 14C-labeled virus were identical to those of stained gels. Two glycoproteins constituting 25% of the virion protein were identified by bromelin digestion as the spike proteins. The density in sucrose and in potassium tartrate was 1.18 g/ml for the virion and 1.15 g/ml for the “despiked” particle.


Acute febrile respiratory infection symptoms in Australian Hajjis at risk of exposure to Middle East respiratory syndrome coronavirus


title: Infectious bronchitis virus in different avian physiological systems—A field study in Brazilian poultry flocks

text: Abstract Avian infectious bronchitis is a highly contagious viral disease with economic effects on poultry agribusiness. The disease presents multi-systemic clinical signs (respiratory, renal, enteric, and reproductive) and is caused by one coronavirus (infectious bronchitis virus, IBV). Infectious bronchitis virus is classified into different serotypes and genotypes (vaccine strains and field variants). This study aimed to evaluate the occurrence of IBV in commercial poultry flocks from 3 important producing regions in Brazil and to determine the tropism of the main circulating genotypes to 3 different avian physiological systems (respiratory, digestive, urinary/reproductive). Clinical samples with suggestive signs of IBV infection were collected from 432 different poultry commercial flocks (198 from broilers and 234 from breeders). The total number of biological samples consisted of organ pools from the 3 above physiological systems obtained of farms from 3 important producing regions: midwest, northeast, and south. Infectious bronchitis virus was detected by reverse-transcription, real-time PCR of the 5′ untranslated region. The results showed 179 IBV-positive flocks (41.4% of the flocks), with 107 (24.8%) from broilers and 72 (16.8%) from breeders. There were similar frequencies of IBV-positive flocks in farms from different regions of the country, most often in broilers (average 54%) compared with breeders (average 30.8%). reverse-transcription was more frequently detected in the digestive system of breeders (40%), and in the digestive (43.5%) and respiratory (37.7%) systems of broilers. Infectious bronchitis virus genotyping was performed by a reverse-transcription nested PCR and sequencing of the S1 gene from a selection of 79 IBV-positive flocks (45 from broilers and 34 from breeders). The majority of the flocks were infected with Brazilian variant genotype than with Massachusetts vaccine genotype. These results demonstrate the predominance of the Brazilian variant (mainly in the enteric tract) in commercial poultry flocks from 3 important producing regions in Brazil.


title: Identification of novel bovine group A rotavirus G15P[14] strain from epizootic diarrhea of adult cows by de novo sequencing using a next-generation sequencer

text: Abstract There are few reports describing diarrhea of adult cattle caused by group A rotaviruses. Here, we report the identification of a novel bovine group A rotavirus from diarrhea of adult cows. A group A rotavirus was detected from an epizootic outbreak of diarrhea in adult cows with a decrease in milk production in Japan in 2013. The comprehensive genomic analyses from fecal samples by viral metagenomics using a next-generation sequencer revealed that it had an unreported genotype combination G15P[14]. The genome constellation of this strain, namely, RVA/Cow-wt/JPN/Tottori-SG/2013/G15P[14] was G15-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3 representing VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Each gene segment of Tottori-SG was most closely related to Japanese bovine group A rotaviruses suggesting that Tottori-SG might have derived from multiple reassortment events from group A rotavirus strains circulating among Japanese cattle. No other diarrhea pathogen of adult cattle was detected by routine diagnosis and metagenomics. Viral metagenomics, using a next-generation sequencer, is useful to characterize group A rotaviruses from fecal samples and offers unbiased comprehensive investigations of pathogen.


title: Potential Benefits of Combination of Nigella sativa and Zn Supplements to Treat COVID-19

text: An effective vaccine to prevent the SARS-CoV-2 causing COVID-19 is yet to be approved. Further there is no drug that is specific to treat COVID-19. A number of antiviral drugs such as Ribavirin, Remdesivir, Lopinavir/ritonavir, Azithromycin and Doxycycline have been recommended or are being used to treat COVID-19 patients. In addition to these drugs, rationale and evidence have been presented to use chloroquine to treat COVID-19, arguably with certain precautions and criticism. In line with the proposed use of chloroquine, Nigella sativa (black seed) could be considered as a natural substitute that contains a number of bioactive components such as thymoquinone, dithymoquinone, thymohydroquinone, and nigellimine. Further benefits to use N. sativa could be augmented by Zn supplement. Notably, Zn has been proven to improve innate and adaptive immunity in the course of any infection, be it by pathogenic virus or bacteria. The effectiveness of the Zn salt supplement could also be enhanced with N. sativa as its major bioactive component might work as ionophore to allow Zn2+ to enter pneumocytes - the target cell for SARSCoV-2. Given those benefits, this review paper describes how N. sativa in combination with Zn could be useful as a complement to COVID-19 treatment.


title: Metalloproteinases in biology and pathology of the nervous system

text: Matrix metalloproteinases (MMPs) have been implicated in several diseases of the nervous system. Here we review the evidence that supports this idea and discuss the possible mechanisms of MMP action. We then consider some of the beneficial functions of MMPs during neural development and speculate on their roles in repair after brain injury. We also introduce a family of proteins known as ADAMs (a disintegrin and metalloproteinase), as some of the properties previously ascribed to MMPs are possibly the result of ADAM activity.


COVID-19: Compounding the health-related harms of human trafficking


title: Post-mortem surveillance of bovine tuberculosis in Ireland: herd-level variation in the probability of herds disclosed with lesions at routine slaughter to have skin test reactors at follow-up test

text: Post-mortem surveillance in Ireland discloses skin-test negative cattle with presumptive evidence of infection of Mycobacterium bovis (lesions at routine slaughter (LRS)), the causative agent of bovine tuberculosis (bTB). Laboratory confirmation of lesions has impacts on trade restrictions for herds, therefore if laboratory capacity was diminished, how herds are treated would require an informed risk policy. Here we report the proportion of herds with subsequent evidence of within-herd transmission, based on skin-test results. We assess how herd-size, herd-type, and bTB-history affect the probability of additional reactors at follow-up test using univariable and multivariable random-effects models. The study represents a rapid response to developing an evidential base for policy demands during an extraordinary event, the COVID-19 epidemic in Ireland. A dataset from 2005 to 2019 of breakdowns were collated. Overall, 20,116 breakdowns were initiated by LRS cases. During the index tests of these breakdowns, 3931 revealed ≥1 skin-test reactor animals (19.54%; ≥1 standard reactors: 3827; 19.02%). Increasing herd-size was associated with reactor disclosure on follow-up. For small herds (<33 animals), 11.74% of follow-up tests disclosed ≥1 reactor; 24.63% of follow-up tests from very large herds (>137) disclosed ≥1 reactors. Beef (13.87%) and “other” (13%) herd production types had lower proportion of index tests with reactors in comparison with dairy (28.27%) or suckler (20.48%) herds. Historic breakdown size during the previous 3-years was associated reactor disclosure risk on follow-up. Our results are useful for rapid tailored policy development aimed at identifying higher risk herds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11259-020-09777-w) contains supplementary material, which is available to authorized users.


title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification

text: Abstract Rapid detection of SARS-CoV-2 is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel “2019 Novel Coronavirus Detection Kit (nCoV-DK)” halves detection time by eliminating the steps of RNA extraction and purification. We evaluated concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 (74.6%) and 55/71 (77.5%) by the direct PCR and nCoV-DK, respectively, with overall concordance rate of 94.4%: 95.2% in nasopharyngeal swab, 95.5% in saliva, and 85.7% in sputum. The nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error.


title: Gastrointestinal Endoscopy Infection Control Strategy during COVID‐19 Pandemic: experience from a tertiary medical center in China

text: OBJECTIVES: COVID‐19 has spread globally and become a pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) not only infects the gastrointestinal (GI) tract and causes GI symptoms, but also increases nosocomial transmission risk during endoscopic procedures for aerosol generation. We hereby share our infection control strategies aiming to minimize COVID‐19 transmission in the endoscopy center. METHODS: We established our infection control strategies based on the guidance of Chinese Society of Digestive Endoscopy and inputs from hospital infection control experts: admission control through the procedure and patient triage, environmental control to reduce possible virus exposure, proper usage of personal protective equipment (PPE), and scope disinfection and room decontamination. All endoscopic procedures accomplished during COVID‐19 outbreak and progress of stepwise resumption of elective endoscopy procedures were retrospectively reviewed. RESULTS: Only urgent or semi‐urgent procedures were performed during COVID‐19 outbreak. After no local new‐onset COVID‐19 case in Beijing for four weeks, we reopened the endoscopy center for elective procedures and monitored the outbreak continuously while maintaining a sustainable endoscopy service. CONCLUSIONS: It is imperative that all endoscopy centers should establish standard infection control strategies in order to fight COVID‐19 pandemic based on national guidance and academic society guidelines and tailored them to individual resources. These measures and setup can also be reserved for future pandemics.


title: Senate approves coronavirus relief bill

text: The U.S. Senate approved an estimated $2 trillion stimulus package to battle the harmful effects of the COVID‐19 pandemic, though concerns with the unemployment provisions remain, according to the National Conference of State Legislature. A few highlights of what's included in the package.


title: COVID-19: A tale of two pandemics across the Asia Pacific region

text: The widely diverse impacts of SAR-CoV-2 infection resulting in the COVID-19 pandemic cannot be held in more stark relief when contrasting the devastating impact upon China, Italy, Great Britain, America and Brazil with the considerably milder course in the geographically isolated countries of Australia and New Zealand and the densely populated Vietnam. Children in the Asia-Pacific region, as with children all over the world to date, have fared better than older adults. Other countries in the Asia-Pacific region, including Indonesia and India have struggled to deal with the pandemic because of a lack of health infrastructure, inability to provide sufficient testing and isolation and widespread poverty. This article will provide a snapshot of the impact of COVID-19 upon countries in the Asia-Pacific region in the six months since the first case of the novel zoonotic coronavirus infection appeared in China.


title: Association of New Coronavirus Disease with Fragility Hip and Lower Limb Fractures in Elderly Patients

text: The novel coronavirus-induced infection (COVID-19) was declared a pandemic by the World Health Organization on March 11, 2020 Iran is one of the countries with a high incidence of COVID-19 infection Data on three patients with fragility hip fracture and COVID-19 infection were collected from one hospital located in Badrud, Isfahan, Iran, from March 1, 2010, to March 30, 2020 All patients were elderly and had fracture induced by fall from standing height All patients (n=3) were admitted with fragility hip fracture due to low energy trauma The most common symptoms were weakness and fatigue Positive C-reactive protein (CRP) and Leukopenia were the most common abnormal laboratory evaluations According to the results, two patients underwent surgical treatment, and one patient had negative reverse transcription-CRP;however, all of them underwent medical treatment for COVID-19 infection There is a possible relationship between COVID-19 infection and fragility hip fracture in elderly patients It could be induced by fatigue and weakness due to COVID-19 disease COVOID-19 infection should be considered in elderly patients with fragility hip fracture during the coronavirus pandemic


title: ”For this one, let me take the risk”: why surgical staff continued to perform caesarean sections during the 2014–2016 Ebola epidemic in Sierra Leone

text: INTRODUCTION: Routine health service provision decreased during the 2014–2016 Ebola virus disease (EVD) outbreak in Sierra Leone, while caesarean section (CS) rates at public hospitals did not. It is unknown what made staff provide CS despite the risks of contracting EVD. This study explores Sierra Leonean health worker perspectives of why they continued to provide CS. METHODS: This qualitative study documents the experiences of 15 CS providers who worked during the EVD outbreak. We interviewed surgical and non-surgical CS providers who worked at public hospitals that either increased or decreased CS volumes during the outbreak. Hospitals in all four administrative areas of Sierra Leone were included. Semistructured interviews averaged 97 min and healthcare experience 21 years. Transcripts were analysed by modified framework analysis in the NVivo V.11.4.1 software. RESULTS: We identified two themes that may explain why providers performed CS despite EVD risks: (1) clinical adaptability and (2) overcoming the moral dilemmas. CS providers reported being overworked and exposed to infection hazards. However, they developed clinical workarounds to the lack of surgical materials, protective equipment and standard operating procedures until the broader international response introduced formal personal protective equipment and infection prevention and control practices. CS providers reported that dutifulness and sense of responsibility for one’s community increased during EVD, which helped them justify taking the risk of being infected. Although most surgical activities were reduced to minimise staff exposure to EVD, staff at public hospitals tended to prioritise performing CS surgery for women with acute obstetric complications. CONCLUSION: This study found that CS surgery during EVD in Sierra Leone may be explained by remarkable decisions by individual CS providers at public hospitals. They adapted practically to material limitations exacerbated by the outbreak and overcame the moral dilemmas of performing CS despite the risk of being infected with EVD.


title: Forecasting smog-related health hazard based on social media and physical sensor

text: Abstract Smog disasters are becoming more and more frequent and may cause severe consequences on the environment and public health, especially in urban areas. Social media as a real-time urban data source has become an increasingly effective channel to observe people׳s reactions on smog-related health hazard. It can be used to capture possible smog-related public health disasters in its early stage. We then propose a predictive analytic approach that utilizes both social media and physical sensor data to forecast the next day smog-related health hazard. First, we model smog-related health hazards and smog severity through mining raw microblogging text and network information diffusion data. Second, we developed an artificial neural network (ANN)-based model to forecast smog-related health hazard with the current health hazard and smog severity observations. We evaluate the performance of the approach with other alternative machine learning methods. To the best of our knowledge, we are the first to integrate social media and physical sensor data for smog-related health hazard forecasting. The empirical findings can help researchers to better understand the non-linear relationships between the current smog observations and the next day health hazard. In addition, this forecasting approach can provide decision support for smog-related health hazard management through functions like early warning.