title: Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5–13 Years

text: We detected human metapneumovirus (HMPV) in 54 (5%) of 1055 children aged 5 to 13 years with acute respiratory illness (ARI) identified by outpatient and emergency department surveillance between November and May 2003–2009. Its clinical features were similar to those of HMPV-negative ARI, except a diagnosis of pneumonia was more likely (13% vs 4%, respectively; P = .005) and a diagnosis of pharyngitis (7% vs 24%, respectively; P = .005) was less likely in patients with HMPV- positive ARI than those with HMPV-negative ARI.


title: Structural and Functional Insights into Small, Glutamine-Rich, Tetratricopeptide Repeat Protein Alpha

text: The small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA) is an emerging player in the quality control of secretory and membrane proteins mislocalized to the cytosol, with established roles in tail-anchored (TA) membrane protein biogenesis. SGTA consists of three structural domains with individual functions, an N-terminal dimerization domain that assists protein sorting pathways, a central tetratricopeptide repeat (TPR) domain that mediates interactions with heat-shock proteins, proteasomal, and hormonal receptors, and viral proteins, and a C-terminal glutamine rich region that binds hydrophobic substrates. SGTA has been linked to viral lifecycles and hormone receptor signaling, with implications in the pathogenesis of various disease states. Thus far, a range of biophysical techniques have been employed to characterize SGTA structure in some detail, and to investigate its interactions with binding partners in different biological contexts. A complete description of SGTA structure, together with further investigation into its function as a co-chaperone involved quality control, could provide us with useful insights into its role in maintaining cellular proteostasis, and broaden our understanding of mechanisms underlying associated pathologies. This review describes how some structural features of SGTA have been elucidated, and what this has uncovered about its cellular functions. A brief background on the structure and function of SGTA is given, highlighting its importance to biomedicine and related fields. The current level of knowledge and what remains to be understood about the structure and function of SGTA is summarized, discussing the potential direction of future research.


title: Systemic resilience to cross‐border infectious disease threat events in Europe

text: Recurrent health emergencies threaten global health security. International Health Regulations (IHR) aim to prevent, detect and respond to such threats, through increase in national public health core capacities, but whether IHR core capacity implementation is necessary and sufficient has been contested. With a longitudinal study we relate changes in national IHR core capacities to changes in cross‐border infectious disease threat events (IDTE) between 2010 and 2016, collected through epidemic intelligence at the European Centre for Disease Prevention and Control (ECDC). By combining all IHR core capacities into one composite measure we found that a 10% increase in the mean of this composite IHR core capacity to be associated with a 19% decrease (p = 0.017) in the incidence of cross‐border IDTE in the EU. With respect to specific IHR core capacities, an individual increase in national legislation, policy & financing; coordination and communication with relevant sectors; surveillance; response; preparedness; risk communication; human resource capacity; or laboratory capacity was associated with a significant decrease in cross‐border IDTE incidence. In contrast, our analysis showed that IHR core capacities relating to point‐of‐entry, zoonotic events or food safety were not associated with IDTE in the EU. Due to high internal correlations between core capacities, we conducted a principal component analysis which confirmed a 20% decrease in risk of IDTE for every 10% increase in the core capacity score (95% CI: 0.73, 0.88). Globally (EU excluded), a 10% increase in the mean of all IHR core capacities combined was associated with a 14% decrease (p = 0.077) in cross‐border IDTE incidence. We provide quantitative evidence that improvements in IHR core capacities at country‐level are associated with fewer cross‐border IDTE in the EU, which may also hold true for other parts of the world.


title: The Emerging Role of Convalescent Plasma in the Treatment of COVID-19

text: Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID-19). Plasma from patients that have overcome COVID-19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID-19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non-randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion-related acute lung injury and antibody-dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.


Air pollution, racial disparities and COVID-19 mortality


docid: lqoyxbln

title: International Survey of Trials of Convalescent Plasma to Treat COVID-19 Infection

text: Abstract The collection and clinical use of COVID-19 convalescent plasma (CCP) as a therapy for COVID-19 infection is under development and early use in many centers worldwide. We conducted an international survey of centers undertaking studies of CCP to provide understanding of the common themes and differences between them. 64 studies in 22. countries were identified from clinical trial registries and personal contacts of the authors. 20 of the 64 centers (31%) from 12 of 22 countries (55%) responded to the survey. Of the 20 studies, 11 were randomized controlled trials (RCTs) and 9 were case series. Only 4 of the RCTs plan to recruit 400 patients or more, and only 3 RCTs were blinded. The majority of studies will study the effect of CCP on sick patients requiring hospitalization and those requiring critical care, and none is examining the role of CCP in non-infected at-risk individuals. A wide variety of primary and secondary outcomes are being used. The donor eligibility criteria among the studies are very similar, and the use of plasmapheresis for the collection of CCP is almost universal. The planned dose of CCP ranges from as little as 200mL to well over 1 liter, but is 400-800 mL or 4 mL/kg or greater in all the RCTs. There is considerable variability in donor antibody testing with no consistency regarding the cut-off for antibody titer for acceptance as CCP or the use of pathogen-inactivation. Our survey provides an understanding of the similarities and differences among the studies of CCP, and that by virtue of their design some studies may be more informative than others.


title: Preparation of Recombinant Alphaviruses for Functional Studies of ADP-Ribosylation

text: Recently we characterized the mono(ADP-ribosyl) hydrolase (MAR hydrolase) activity of the macrodomain of nonstructural protein 3 (nsP3(MD)) of chikungunya virus. Using recombinant viruses with targeted mutations in the macrodomain, we demonstrated that hydrolase function is important for viral replication in cultured neuronal cells and for neurovirulence in mice. Here, we describe the general cell culture and animal model infection protocols for alphaviruses and the technical details for biochemical characterization of the MAR hydrolase activity of nsP3(MD) mutants and the preparation of recombinant viruses incorporating those mutations through site-directed mutagenesis of an infectious cDNA virus clone.


docid: vpspaxmx

title: Comparative Pancreatic Pathology

text: Abstract Spontaneous pathologies of the pancreas are important causes of morbidity and mortality in some veterinary species and rare in others. As in human beings, the pancreas of most domestic and exotic animals is a composite organ with both endocrine and exocrine functions. The similarities between structure and function of porcine, canine, and human pancreata are such that the pig and dog serve as valuable models in basic and translational studies, most recently for efforts aimed at modeling pancreatitis and diabetes, developing functional and sustainable replacement of endocrine functions, and in imaging and manipulation studies. This article will provide a brief review of spontaneous veterinary diseases and their underlying mechanisms and the morphological features that reflect these alterations. Several species- or breed-specific conditions and the effects of selected systemic diseases on the pancreas are also discussed. The contributions to our knowledge of pancreatic physiology and pathology by small mammal (rodent) and engineered animal models and the in-depth mechanisms homologous to those in the human pancreas are covered in other sections of this article.


title: Stand Together and Deliver: Challenges and Opportunities for Rheumatology Education During the COVID‐19 Pandemic

text: In a matter of weeks, the COVID19 crisis has totally upended clinical medicine and the practice of rheumatology. Our old ways of seeing patients in person, precepting fellows in clinic or on the consult service, and leading in-person interactive teaching rounds are gone for now and possibly for good. But how can we replace these critical teaching and training elements? Despite the mounting challenges of managing an exploding population of coronavirus infected patients and caregivers, we must find innovative ways to foster our trainees' professional development.


title: Development of a pseudovirus based assay for measuring neutralizing antibodies against coxsackievirus B5

text: Abstract Coxsackievirus B5 (CV-B5), an important Coxsackie B virus from genus Enteroviruse within the family Picornaviridae, has also been isolated from Hand, Foot, and Mouth Disease (HFMD) patients, and often associated with neurological manifestations. In this study, we found out that Coxsackievirus B3 (CV-B3) replicon RNA could be encapsidated with CV-B5 capsid to assemble infectious CV-B5 pseudovirus. We then utilized this single round infection system of CV-B5 to develop a neutralizing antibody quantification assay. This pseudovirus neutralization assay showed superiority in biosafety, sensibility, quantitativity, efficiency and high throughput, and would facilitate the epidemiological studies and vaccine development of CV-B5.


Low dose radiation therapy for COVID-19 pneumonia: a double-edged sword


title: SWOT analysis and revelation in traditional Chinese medicine internationalization

text: Traditional Chinese medicine (TCM) is currently the best-preserved and most influential traditional medical system with the largest number of users worldwide. In recent years, the trend of TCM adoption has increased greatly, but the process of TCM internationalization has suffered from a series of setbacks for both internal and external reasons. Thus, the process of TCM internationalization faces formidable challenges, although it also has favourable opportunities. Using SWOT analysis, this paper investigates the strengths, weaknesses, opportunities and threats for TCM. These findings can serve as references for TCM enterprises with global ambitions.


Challenges with using names to link digital biodiversity information


title: Differential Diagnosis of Common Acute Toxicologic Versus Nontoxicologic Illness

text: This article provides a display table laying out the differential diagnosis of common acute toxicologic versus nontoxicologic illnesses in small animals. Major clinical abnormalities are listed, along with common toxicologic rule outs and nontoxicologic rule outs. Further readings are also provided.


docid: knvabdsg

title: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion


title: Validation and application of normalization factors for gene expression studies in rubella virus‐infected cell lines with quantitative real‐time PCR

text: Reference genes are generally employed in real‐time quantitative PCR (RT‐qPCR) experiments to normalize variability between different samples. The aim of this study was to identify and validate appropriate reference genes as internal controls for RT‐qPCR experiments in rubella virus (RV)‐infected Vero and MCF‐7 cell lines using SYBR green fluorescence. The software programs geNorm and NormFinder and the ΔΔC(t) calculation were used to determine the expression stability and thus reliability of nine suitable reference genes. HPRT1 and HUEL, and HUEL and TBP were identified to be most suitable for RT‐qPCR analysis of RV‐infected Vero and MCF‐7 cells, respectively. These genes were used as normalizers for transcriptional activity of selected cellular genes. The results confirm previously published microarray and Northern blot data, particularly on the transcriptional activity of the cyclin‐dependent kinase inhibitor p21 and the nuclear body protein SP100. Furthermore, the mRNA level of the mitochondrial protein p32 is increased in RV‐infected cells. The effect on cellular gene transcription by RV‐infection seems to be cell line‐specific, but genes of central importance for viral life cycle appear to be altered to a similar degree. This study does not only provide an accurate and flexible tool for the quantitative analysis of gene expression patterns in RV‐infected cell lines. It also indicates, that the suitability of a reference gene as normalizer of RT‐qPCR data and the host‐cell response to RV‐infection are strictly cell‐line specific. J. Cell. Biochem. 110: 118–128, 2010. © 2010 Wiley‐Liss, Inc.


title: Non‐immediate hypersensitivity reactions to beta‐lactam antibiotics in children – our 10‐year experience in allergy work‐up

text: BACKGROUND: Non‐immediate reactions to beta‐lactam antibiotics (BL) occur more than one hour after drug administration, and the most common manifestations are maculopapular exanthemas and delayed‐appearing urticaria and/or angioedema. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions (DHR), if a drug is taken at the same time. The most of children are labeled as ‘drug allergic’ after considering only the clinical history. OBJECTIVE: To diagnose/detect a hypersensitivity or an infection which mimic DHR in children with non‐immediate reactions to BL METHODS: A prospective survey was conducted in a group of 1026 children with histories of non‐immediate reactions to BL by performing patch tests, skin tests, and in case of negative results, drug provocation tests (DPTs). In 300 children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. RESULTS: Urticaria and maculopapular exanthemas were the most reported non‐immediate reactions. Only 76 (7.4%) of 1026 children had confirmed non‐immediate hypersensitivity reactions to BL. Fifty‐seven children had positive delayed‐reading intradermal tests (18 of these with a positive patch test). Nineteen children had positive DPT. Sixty‐six of 300 children had positive tests for viruses or Mycoplasma pneumoniae and 2 of them had a positive allergy work‐up. CONCLUSIONS: A diagnostic work‐up should be performed in all children with non‐immediate reactions to BL, to remove a false label of hypersensitivity. Even though only 57 (5.5%) of 1026 children displayed positive responses to delayed‐reading intradermal tests to BL, such tests appear to be useful in order to reduce the risk for positive DPTs.


title: Role of China in the Quest to Define and Control Severe Acute Respiratory Syndrome

text: China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may then be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome. There must be support for systematically addressing these fundamental questions in China and rapidly disseminating results.


title: Inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using amotosalen and ultraviolet A light

text: BACKGROUND: The INTERCEPT Blood System pathogen reduction technology (PRT), which uses amotosalen and ultraviolet A light treatment (amotosalen/UV‐PRT), inactivates pathogens in plasma and platelet components (PCs). This review summarizes data describing the inactivation efficacy of amotosalen/UVA‐PRT for a broad spectrum of viruses and parasites. METHODS: Twenty‐five enveloped viruses, six nonenveloped viruses (NEVs), and four parasites species were evaluated for sensitivity to amotosalen/UVA‐PRT. Pathogens were spiked into plasma and PC at high titers. Samples were collected before and after PRT and assessed for infectivity with cell cultures or animal models. Log reduction factors (LRFs) were defined as the difference in infectious titers before and after amotosalen/UV‐PRT. RESULTS: LRFs of ≥4.0 log were reported for 19 pathogens in plasma (range, ≥4.0 to ≥7.6), 28 pathogens in PC in platelet additive solution (PC‐PAS; ≥4.1‐≥7.8), and 14 pathogens in PC in 100% plasma (PC‐100%; (≥4.3‐>8.4). Twenty‐five enveloped viruses and two NEVs were sensitive to amotosalen/UV‐PRT; LRF ranged from >2.9 to ≥7.6 in plasma, 2.4 or greater to greater than 6.9 in PC‐PAS and >3.5 to >6.5 in PC‐100%. Infectious titers for four parasites were reduced by >4.0 log in all PC and plasma (≥4.9 to >8.4). CONCLUSION: Amotosalen/UVA‐PRT demonstrated effective infectious titer reduction for a broad spectrum of viruses and parasites. This confirms the capacity of this system to reduce the risk of viral and parasitic transfusion‐transmitted infections by plasma and PCs in various geographies.


title: Corona virus versus existence of human on the earth: A computational and biophysical approach

text: SARS-CoV-2 has a positive sense RNA genome of 29.9 kb in size, showing high sequence similarity to the BAT-CoV, SARS-CoV, MERS-CoV. SARS-CoV-2 is composed of 14 open reading frames (ORFs), which encodes for a total of 27 proteins divided into structural and non-structural proteins (NSPs). The fundamental structural protein-encoding genes are a spike protein (S) gene, envelope protein (E) gene, a membrane protein (M) gene, and a nucleocapsid protein (N) gene. They make about 33% of the entire genome and are vital for the viral life cycle. Rest 67% is distributed among different NSPs (such as M(pro), helicase, and RNA-dependent RNA polymerase) encoding genes across the ORFs, which are involved in virus-cell receptor interactions during viral entry. Researchers are trying to formulate vaccines, therapeutic antibodies or protein-targeted antiviral drugs to control the spread. This review proceeds stepwise through the COVID-19 outbreak, structural and genomic organization, entry mechanism, pathogenesis, and finally highlighting the essential proteins involved at each step that might be potential targets for drug discovery. Currently, approved treatment modalities consist of only supportive care and oxygen supplementation. This review is established on the current knowledge that has expanded on structural motifs and topology of proteins and their functions.


SDF − a game changer?


title: Force of infection of Middle East respiratory syndrome in dromedary camels in Kenya

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease transmitted from dromedary camels to people, which can result in outbreaks with human-to-human transmission. Because it is a subclinical infection in camels, epidemiological measures other than prevalence are challenging to assess. This study estimated the force of infection (FOI) of MERS-CoV in camel populations from age-stratified serological data. A cross-sectional study of MERS-CoV was conducted in Kenya from July 2016 to July 2017. Seroprevalence was stratified into four age groups: <1, 1–2, 2–3 and >3 years old. Age-independent and age-dependent linear and quadratic generalised linear models were used to estimate FOI in pastoral and ranching camel herds. Models were compared based on computed AIC values. Among pastoral herds, the age-dependent quadratic FOI was the best fit model, while the age-independent FOI was the best fit for the ranching herd data. FOI provides an indirect estimate of infection risk, which is especially valuable where direct estimates of incidence and other measures of infection are challenging to obtain. The FOIs estimated in this study provide important insight about MERS-CoV dynamics in the reservoir species, and contribute to our understanding of the zoonotic risks of this important public health threat.


title: Airway gene transfer using cationic emulsion as a mucosal gene carrier

text: BACKGROUND: Delivery of genes to airway mucosa would be a very valuable method for gene therapy and vaccination. However, there have been few reports on suitable gene delivery systems for administration. In this study, we use a cationic emulsion system, which is physically stable and facilitates the transfer of genes in the presence of up to 90% serum, as a mucosal gene carrier. METHODS AND RESULTS: Cationic lipid emulsion was formulated with squalene and 1,2‐dioleoyl‐sn‐glycero‐3‐trimethylammoniumpropane (DOTAP) as major components. Emulsions formed stable complexes with DNA and protected and transferred DNA to target cells against DNase I digestion in the presence of mucosal destabilizers such as heparin sulfate (a polysaccharide of the glycosaminoglycan family in mucosa) and Newfectan (a natural lung extract of bovine) in an in vitro system. In contrast, commercial liposomes and counter liposomes, made with an identical lipid composition of emulsions, failed. After in vivo intranasal instillation, the cationic emulsion showed at least 200 times better transfection activity than the liposomal carriers in both nasal tissue and lung. CONCLUSIONS: These findings show that cationic emulsions can mediate gene transfection into airway epithelium, making it a good choice for transferring therapeutic genes and for genetic vaccination against an pathogenic infection via an airway route. Copyright © 2005 John Wiley & Sons, Ltd.


title: ¿Porqué es menos "intensa" la epidemia de Covid-19 en África?

text: Resumen La mayoría de la bibliografía mundial sobre la pandemia Covid-19 se ha focalizado en los países del continente asiático, europeo o americano. En África parece que la incidencia es menor. En este artículo se hipotetiza sobre alguna de las posibles causas que han dado lugar a estas diferencias. La pirámide poblacional, la temperatura ambiente, la vulnerabilidad/resistencia de los habitantes del continente o factores sociopolíticos son subrayados. En caso de que la pandemia se extendiera en el continente africano, posiblemente la falta de recursos sanitarios haría que las consecuencias fueran desastrosas y de una magnitud dantesca. Abstract Most of the international bibliography published on Covid-19 pandemics is focused in the Asian, European or American continents. It seems that incidence is lower in Africa. In this article we hypothetize on several of the possible causes sustaining these differences. Population pyramid, climate, african population own vulnerability/resistance or sociopolitical factors are underlined. In the case the pandemics will spread in Africa, the lack of basic healthcare resources will perhaps make the consequences disastrous and of a dantesque magnitude.


title: RNA methyltransferases involved in 5′ cap biosynthesis

text: In eukaryotes and viruses that infect them, the 5′ end of mRNA molecules, and also many other functionally important RNAs, are modified to form a so-called cap structure that is important for interactions of these RNAs with many nuclear and cytoplasmic proteins. The RNA cap has multiple roles in gene expression, including enhancement of RNA stability, splicing, nucleocytoplasmic transport, and translation initiation. Apart from guanosine addition to the 5′ end in the most typical cap structure common to transcripts produced by RNA polymerase II (in particular mRNA), essentially all cap modifications are due to methylation. The complexity of the cap structure and its formation can range from just a single methylation of the unprocessed 5′ end of the primary transcript, as in mammalian U6 and 7SK, mouse B2, and plant U3 RNAs, to an elaborate m(7)Gpppm(6,6)AmpAmpCmpm(3)Um structure at the 5′ end of processed RNA in trypanosomes, which are formed by as many as 8 methylation reactions. While all enzymes responsible for methylation of the cap structure characterized to date were found to belong to the same evolutionarily related and structurally similar Rossmann Fold Methyltransferase superfamily, that uses the same methyl group donor, S-adenosylmethionine; the enzymes also exhibit interesting differences that are responsible for their distinct functions. This review focuses on the evolutionary classification of enzymes responsible for cap methylation in RNA, with a focus on the sequence relationships and structural similarities and dissimilarities that provide the basis for understanding the mechanism of biosynthesis of different caps in cellular and viral RNAs. Particular attention is paid to the similarities and differences between methyltransferases from human cells and from human pathogens that may be helpful in the development of antiviral and antiparasitic drugs.


docid: wfftfkam

title: COVID‐19 is milder in children possibly due to cross immunity

text: It has been unclear why the new severe acute respiratory syndrome coronavirus (sars‐CoV‐2) hits a small minority hard, while the vast majority of children appear to be protected and develop mild or no disease (1,2). The editorial by Brodin suggests some possible mechanisms why it is so (1). I would like to emphasize the significance of cross immunity due to previous exposure to seasonal coronavirus; it may be a plausible explanation for why children appear to be protected (2,3).


docid: kqithgfo

title: E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns

text: DNA microarrays may be used to identify microbial species present in environmental and clinical samples. However, automated tools for reliable species identification based on observed microarray hybridization patterns are lacking. We present an algorithm, E-Predict, for microarray-based species identification. E-Predict compares observed hybridization patterns with theoretical energy profiles representing different species. We demonstrate the application of the algorithm to viral detection in a set of clinical samples and discuss its relevance to other metagenomic applications.


title: Angiotensin‐converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor

text: Angiotensin‐converting enzyme 2 (ACE2) is thought to act in an opposing manner to its homologue, angiotensin‐converting enzyme (ACE), by inactivating the vasoconstrictor peptide angiotensin II and generating the vasodilatory fragment, angiotensin(1–7). Both ACE and ACE2 are membrane‐bound ectoenzymes and may circulate in plasma as a consequence of a proteolytic shedding event. In this study, we show that ACE2 circulates in human plasma, but its activity is suppressed by the presence of an endogenous inhibitor. Partial purification of this inhibitor indicated that the inhibitor is small, hydrophilic and cationic, but not a divalent metal cation. These observations led us to develop a method for removal of the inhibitor, thus allowing detection of plasma ACE2 levels using a sensitive quenched fluorescent substrate‐based assay. Using this technique, ACE2 activity measured in plasma from healthy volunteers (n= 18) ranged from 1.31 to 8.69 pmol substrate cleaved min(−1) ml(−1) (mean ±s.e.m., 4.44 ± 0.56 pmol min(−1) ml(−1)). Future studies of patients with cardiovascular, renal and liver disease will determine whether plasma ACE2 is elevated in parallel with increased tissue levels observed in these conditions.


title: MERS-CoV: Understanding the Latest Human Coronavirus Threat

text: Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012, a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure; (ii) clinical features; (iii) diagnosis of infection; and (iv) treatment and vaccine development.


title: The Complex Role of STAT3 in Viral Infections

text: Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed.


The characterisation of the virion RNA of avian Infectious Bronchitis Virus


Letter to the Editor: How Did We Solve the Risk of Cross-Infection after Testing by the Walk-Through System Pointed Out by Many Authors?


title: Masks and closed-loop ventilators prevent environmental contamination by COVID-19 patients in negative-pressure environments

text: Abstract Herein, we report that nosocomial infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be mitigated by using surgical masks and closed looped ventilation for both non-critical and critical patients. These preventive measures resulted in no viral contamination of surfaces in negative pressure environments.


title: Collection and review of updated scientific epidemiological data on porcine epidemic diarrhoea

text: Porcine epidemic diarrhoea (PED) is a non‐zoonotic viral disease of pigs caused by a coronavirus and characterised by watery diarrhoea and weight loss. PED is not notifiable to the EU or World Organisation for Animal Health listed but it is notifiable at the national level in Finland, France, Ireland and Sweden. PED case reports from seven countries and PED surveillance and monitoring activities in thirteen countries were reported. This information was combined with an extensive literature review to provide an update on global PED occurrence, circulating strains and impact in 2014–2015. PED confirmed cases have been reported in North America, South America, Asia and Europe. PED virus (PEDV) sequences originating from EU pig herds indicate that the strains currently in circulation share nearly 100% sequence identity and have greater than 99% sequence identity with the reference INDEL (insertion/deletion) strain USA/OH851/2014. In 2014–2015, greater genetic variability has been reported in strains circulating in Asia compared with EU Member States and a non‐INDEL strain has been detected in the Ukraine in 2014. Data on impact confirms that mortality is higher in suckling piglets and diarrhoea is observed in all age groups. The reported impact is in agreement with that reported in EFSA AHAW Panel (2014) indicating that the impact of recently reported PED outbreaks in Asia and the USA seems to be more severe than that described in EU countries, although the impact of different PEDV strains is difficult to compare between one country and another, as impact is dependent not only on pathogenicity but also on factors such as biosecurity, herd size, farm management, sanitary status or herd immune status.


title: The Involvement of Natural Killer Cells in the Pathogenesis of Severe Acute Respiratory Syndrome

text: By using peripheral blood samples from 221 cases of severe acute respiratory syndrome (SARS), 34 of Mycoplasma pneumoniae infection, and 44 healthy adults, we measured the total number of natural killer (NK) and CD158b+ NK cells (CD158b+ NK) using flow cytometric analysis and calculated the percentage of CD158b+ NK cells. The total number of NK and CD158b+ NK cells and the percentage of CD158b+ NK cells were significantly lower in patients with SARS than in those with M pneumoniae infection (P < .05 for all) and healthy subjects (P < .01, P < .01, P < .05, respectively); in 72 patients with severe SARS than in 149 with mild SARS (P < .05 for all); and in 174 cases of SARS with anti-SARS coronavirus–specific IgG and/or IgM antibodies than in 47 without antibodies (P < .05, P < .01, P < .01, respectively). There were no significant differences for the 3 values among patients with SARS without anti-SARS coronavirus antibody, patients with M pneumoniae infection, and healthy subjects. The number of NK cells and the expression of CD158b on the surface of NK cells changed in patients with SARS and correlated with disease severity and the presence of anti-SARS coronavirus–specific antibodies; SARS differed from M pneumoniae infection in pathogenesis involving NK cells. Monitoring the total number of NK and CD158b+ NK cells and the percentage of CD158b+ NK cells might aid in differentiating SARS from M pneumoniae infection.


title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

text: Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future.


title: Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria

text: BACKGROUND: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. METHODS: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8(+) T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. RESULTS: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8(+) T cells or CS protein-specific CD8(+) T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. CONCLUSIONS: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-015-0626-2) contains supplementary material, which is available to authorized users.


docid: abcaoqye

title: Covid-19: UK trade talks with EU must not hinder cooperation in tackling threat, BMA warns


title: Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2

text: Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1β, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-β1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1β) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.


title: Provision of dental hospital services during the COVID-19 epidemic

text: Data sources Information about health services provision of public tertiary dental hospitals in China mainland was retrieved through a web search engine. Data analysis The status of non-emergency dental services, emergency dental services and online professional consultation was recorded and analysed. If telehealth was provided, the charge,means of access, service time and service content were investigated. The geographical distribution of hospitals was recorded and classified . Results A total of 48 dental hospitals were included in the study. All 48 dental hospitals suspended general non-emergency dental treatment. They provided emergency dental services only.


title: Protein microarrays: high-throughput tools for proteomics

text: Protein microarrays are versatile tools for parallel, miniaturized screening of binding events involving large numbers of immobilized proteins in a time- and cost-effective manner. They are increasingly applied for high-throughput protein analyses in many research areas, such as protein interactions, expression profiling and target discovery. While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. This article reviews recent developments in the generation of protein microarrays and their applications in proteomics and diagnostics.


title: Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients

text: Abstract The nucleocapsid (N) protein is a structural component of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and can induce antibody responses in SARS patients during infection. However, it is not known whether SARS-CoV N protein can induce a long persistence of memory T-cell response in human. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of overlapping peptides that cover the entire N protein sequence. The N-specific IFN-γ+CD4+ T cells were mainly composed of CD45RA−CCR7+CD62L− cells, whereas IFN-γ+CD8+ memory T cells were mostly contained within CD45RA+CCR7−CD62L− cell population. Epitope mapping study indicated that a cluster of overlapping peptides located in the C-terminal region (amino acids [aa] 331 to 362) of N protein contained at least two different T-cell epitopes. The results indicated that human memory T-cell responses specific for SARS-CoV N protein could persist for 2 years in the absence of antigen, which would be a valuable for the design of effective vaccines against SARS-CoV and for basic studies of human T-cell memory.


title: Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro

text: BACKGROUND: Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). METHODS: Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC(50)) and the selectivity index (SI) were calculated for the extracts and fractions. RESULTS: The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC(50) values of 165.7 ± 3.85 and 126.1 ± 2.80 μg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). CONCLUSIONS: Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2.


Criterios de triaje para reanimación cardiopulmonar y soporte vital avanzado durante la epidemia COVID-19


title: Participation of the IL-10RB Related Cytokines, IL-22 and IFN-λ in Defense of the Airway Mucosal Barrier

text: The airway epithelial barrier is a major barrier protecting against clinically significant infections of the lung. Its integrity is often compromised due to mechanical, chemical, or infectious causes. Opportunistic bacterial pathogens are poised to cause parenchymal infection and become difficult to eradicate due to adaptive metabolic changes, biofilm formation, and the acquisition of antimicrobial resistance and fitness genes. Enhancing mucosal defenses by modulating the cytokines that regulate barrier functions, such as interleukin-22 (IL-22) and interferon-λ (IFN-λ), members of the IL-10 family of cytokines, is an attractive approach to prevent these infections that are associated with high morbidity and mortality. These cytokines both signal through the cognate receptor IL-10RB, have related protein structures and common downstream signaling suggesting shared roles in host respiratory defense. They are typically co-expressed in multiple models of infections, but with differing kinetics. IL-22 has an important role in the producing antimicrobial peptides, upregulating expression of junctional proteins in the airway epithelium and working in concert with other inflammatory cytokines such as IL-17. Conversely, IFN-λ, a potent antiviral in influenza infection with pro-inflammatory properties, appears to decrease junctional integrity allowing for bacterial and immune cell translocation. The effects of these cytokines are pleotropic, with pathogen and tissue specific consequences. Understanding how these cytokines work in the mucosal defenses of the respiratory system may suggest potential targets to prevent invasive infections of the damaged lung.


title: Microbiologic yield of bronchoalveolar lavage specimens from stem cell transplant recipients

text: PURPOSE: Stem cell transplant (SCT) recipients commonly undergo bronchoalveolar lavage (BAL) collection as an infectious pulmonary work‐up. Previous studies report the utility and overall diagnostic yield of fiberoptic bronchoscopy with BAL in this vulnerable population, though none focused purely on microbiologic yield or made comparisons with less invasive means of pathogen detection. We sought to determine and elaborate on the microbiologic yield of BAL in SCT recipients, assess a correlation between BAL studies and less invasive means of pathogen detection, and assess the utility of repeating a BAL within 30 days. METHODS: Between January 1, 2009, and July 31, 2013, we reviewed medical records of 125 SCT recipients who underwent 179 BALs. In addition to demographic information and details pertaining to their SCT, a comprehensive review of their microbiologic data was performed and recorded. RESULTS: Our study showed an overall BAL microbiologic yield of 40%, despite 92% of patients receiving broad‐spectrum antimicrobial therapy at the time of the BAL procedure. CONCLUSIONS: Although an initial BAL sample in this population provides crucial microbiologic information, repeating the procedure within 30 days may have minimal additional microbiologic yield. BAL continues to be an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work‐up.


High prevalence of COVID-19-associated diabetic ketoacidosis in UK secondary care


docid: qmbrswje

title: Civet Cats, Fried Grasshoppers, and David Beckham's Pajamas: Unruly Bodies after SARS

text: This article discusses the viscerality of consumption; in particular, consumption‐as‐eating and consumption‐as‐spending as a set of heterogeneous, contestatory discourses and practices of identity production and subject formation. To do so, I bring together two intersecting events: the Chinese government's ban on wild animal markets during the Severe Acute Respiratory Syndrome (SARS) outbreak, and Chinese and European media frenzy over the visit to China by the Spanish football club Real Madrid in the wake of the epidemic. In discussing these events, I pay specific attention to unruly bodies—both human and nonhuman—as consumables and those who consume them. In examining translocal encounters of these unruly bodies, I suggest that, in post‐SARS China, discourses and practices of consumption produce emergent socialities that at once refigure racialized Orientalist tropes and conjure up discrepant neoliberal imaginaries of lifestyle and consumer choice.


title: Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital

text: OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.


docid: xudxudrc

title: Southeast Asia Strategic Multilateral Dialogue on Biosecurity

text: A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.


title: Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore

text: We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS.


title: Factors associated with the duration of hospitalisation among COVID-19 patients in Vietnam: A survival analysis

text: BACKGROUND: The median duration of hospital stays due to COVID-19 has been reported in several studies on China as 10−13 days. Global studies have indicated that the length of hospitalisation depends on different factors, such as the time elapsed from exposure to symptom onset, and from symptom onset to hospital admission, as well as specificities of the country under study. The goal of this paper is to identify factors associated with the median duration of hospital stays of COVID-19 patients during the second COVID-19 wave that hit Vietnam from 5 March to 8 April 2020. METHOD: We used retrospective data on 133 hospitalised patients with COVID-19 recorded over at least two weeks during the study period. The Cox proportional-hazards regression model was applied to determine the potential risk factors associated with length of hospital stay. RESULTS: There were 65 (48.9%) females, 98 (73.7%) patients 48 years old or younger, 15 (11.3%) persons with comorbidities, 21 (16.0%) severely ill patients and 5 (3.8%) individuals with life-threatening conditions. Eighty-two (61.7%) patients were discharged after testing negative for the SARS-CoV-2 virus, 51 were still in the hospital at the end of the study period and none died. The median duration of stay in a hospital was 21 (IQR: 16–34) days. The multivariable Cox regression model showed that age, residence and sources of contamination were significantly associated with longer duration of hospitalisation. CONCLUSION: A close look at how long COVID-19 patients stayed in the hospital could provide an overview of their treatment process in Vietnam, and support the country's National Steering Committee on COVID-19 Prevention and Control in the efficient allocation of resources over the next stages of the COVID-19 prevention period.


title: A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study

text: Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1–97.9%), specificity 94.3% (95% CI 90.7–98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-3261-3) contains supplementary material, which is available to authorized users.


title: Parasites, Pests, and Pets in a Global World: New Perspectives and Challenges

text: Abstract Taking into account that most of the known living organisms are parasites and that they exert a strong influence on the functioning of ecosystems, we can consider parasitism as a successful strategy for life. Because of the harm that parasites can inflict on man and domesticated animals, which can be expressed as economic loss, many parasites become pests. In natural ecosystems, parasites contribute to the prevention of continuous exponential growth of populations and, therefore, they also need to be conserved. The exotic pet trade may result in translocation of exotic species together with their microparasites and macroparasites, potentiating a risk of transmission of exotic diseases to native fauna and to humans. Within this context we need to increase our knowledge of parasites and parasitic diseases of wildlife. Prevention seems to be the choice for managing parasite exposure. This may be achieved through educational programs that refocused on discouraging people to import exotic pets, together with stronger legislative measures to control wildlife trade.


docid: jqjssnzu

title: A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult

text: Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO(2)/FiO(2) indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.


title: Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve

text: STUDY QUESTION: Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? SUMMARY ANSWER: A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. WHAT IS KNOWN ALREADY: In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) <1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1–90 days after presentation (immediate) or 91–180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH <0.5 and for patients >40 years old with an AMH <1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE: The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH <0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65–1.51) and in patients >40 years old with an AMH <1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77–1.91). LIMITATIONS, REASONS FOR CAUTION: There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS: A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. STUDY FUNDING/COMPETING INTEREST(S): No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.


COVID-19 places Iran’s nomadic pastoralists at a crossroads


title: 4 What is a medical theory?

text: Publisher Summary An account of the nature of medical theories illuminates many aspects of the development and application of medical knowledge. It contributes to the understanding of medical explanation, both at the general level of the causes of diseases and at the individual level of the diagnoses of particular cases of a disease. The syntactic, model-theoretic, paradigm, and third-world accounts fail to capture the complexity of medical theories and explanations. Explanations of a disease do not always need to go down to the deep biochemical level displayed. Depending on the problem and audience at hand, a medical explanation may operate at a superficial level—for example, when physicians tell their patients how they got sick. The most important task in medical research after determining the cause of a disease is developing a treatment for it. While drug discovery used to be largely a matter of serendipity or exhaustive search, current pharmaceutical research is based on a deep understanding of the molecular bases of a disease. Once investigators identify the way defective pathways lead to various diseases, they can search selectively for drugs that correct the defects. Psychology and the other fields of cognitive science have contributed to the powerful theories of mental representation and processing—for example, the theories of concepts, rules, images, and neural networks.


title: Identification of a Novel Coronavirus from Guinea Fowl Using Metagenomics

text: While classical virology techniques such as virus culture, electron microscopy, or classical PCR had been unsuccessful in identifying the causative agent responsible for the fulminating disease of guinea fowl, we identified a novel avian gammacoronavirus associated with the disease using metagenomics. Next-generation sequencing is an unbiased approach that allows the sequencing of virtually all the genetic material present in a given sample.


title: Feline coronavirus with and without spike gene mutations detected by real-time RT-PCRs in cats with feline infectious peritonitis

text: OBJECTIVES: Feline infectious peritonitis (FIP) emerges when feline coronaviruses (FCoVs) mutate within their host to a highly virulent biotype and the immune response is not able to control the infection. FCoV spike (S) gene mutations are considered to contribute to the change in virulence by enabling FCoV infection of and replication in macrophages. This study investigated the presence of FCoV with and without S gene mutations in cats with FIP using two different real-time RT-PCRs on different samples obtained under clinical conditions. METHODS: Fine-needle aspirates (FNAs) and incisional biopsies (IBs) of popliteal and mesenteric lymph nodes, liver, spleen, omentum and kidneys (each n = 20), EDTA blood (n = 13), buffy coat smears (n = 13), serum (n = 11), effusion (n = 14), cerebrospinal fluid (n = 16), aqueous humour (n = 20) and peritoneal lavage (n = 6) were obtained from 20 cats with FIP diagnosed by immunohistochemistry. Samples were examined by RT-PCR targeting the FCoV 7b gene, detecting all FCoV, and S gene mutation RT-PCR targeting mutations in nucleotides 23531 and 23537. The prevalence of FCoV detected in each sample type was calculated. RESULTS: In 20/20 cats, FCoV with S gene mutations was present in at least one sample, but there was variation in which sample was positive. FCoV with mutations in the S gene were most frequently found in effusion (64%, 95% confidence interval [CI] 39–89), followed by spleen, omentum and kidney IBs (50%, 95% CI 28–72), mesenteric lymph node IBs and FNAs (45%, 95% CI 23–67), and FNAs of spleen and liver and liver IBs (40%, 95% CI 19–62). CONCLUSIONS AND RELEVANCE: In these 20 cats with FIP, FCoVs with S gene mutations were found in every cat in at least one tissue or fluid sample. This highlights the association between mutated S gene and systemic FCoV spread. Examining a combination of different samples increased the probability of finding FCoV with the mutated S gene.


title: The curative effects of shortwave diathermy on treating Novel coronavirus (COVID-19) pneumonia: A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: To evaluate the therapeutic effects of ultra-short-wave diathermy (SWD) on COVID-19 pneumonia. The hypothesis is that SWD may minimise pneumonic inflammation and shorten the duration of the time to positive-to-negative conversion of COVID-19 nucleic acid test. TRIAL DESIGN: This is a single centre, 2-arm (1:1 ratio), evaluator blinded, parallel group design superiority randomised, controlled clinical trial. PARTICIPANTS: The inclusion criteria were: (1) Age 18-65 years, (2) COVID-19 nucleic acid test is positive, (3) Lung CT showed multiple patchy ground glass shadows or other typical manifestations of both lungs. The exclusion criteria were: (1) Patients who need ICU management, (2) Positive tests for other pathogens such as Tuberculosis, Mycoplasma, (3) Patients with respiratory failure or requiring mechanical ventilation, (4) Patients with metal implants or pacemakers, (5) Those with shock (6) Those that have bleeding tendency or active bleeding in the lungs, (7) Patients with multiple organ failure who need ICU monitoring and treatment, (8) Cancer patients and those with severe underlying diseases, (9) Pregnant or lactating women, (10) Patients with severe cognitive impairment who cannot follow the instructions to complete the treatment, (11) Those without signed informed consent and (12) Those with other contraindications to short wave. This study will be conducted in Tongji Hospital, Caidian, Wuhan, People’s Republic of China. INTERVENTION AND COMPARATOR: The experimental group will be given the nationally recommended standard medical treatment + ultra-short-wave diathermy treatment. Ultra-short-wave therapy treatment will be performed through application of ultra-short-wave therapy machine electrodes on the anterior and posterior parts of the trunk for 10 minutes, twice a day for 12 consecutive days. The comparator will be the control, not receiving ultra-short-wave therapy, and will be given only the nationally recommended standard medical treatment. MAIN OUTCOMES: The primary outcome measures will be time to positive-to-negative conversion of COVID-19 nucleic acid test by pharyngeal swab, in days assessed at 7(th), 14(th) ,21(st) and 28(th) days. The secondary outcome measures include nucleic acid test rate and recovery from symptoms, Vital signs assessment, Computed Tomography, Complete blood count, serum analysis and SIRS scale scores. Blinded evaluation will be at baseline (the day of starting ultra-short-wave diathermy) and after 28 days following the interventions. RANDOMISATION: A Randomization plan will be generated online on www.randomization.com using permuted blocks method, by a statistician who will not be part of the study. Small blocks of various sizes will be used. Patients will be randomized (1:1) between the experimental and control groups BLINDING (MASKING): This will be an evaluator blinded study. Due to the nature of the intervention, blinding of patients and healthcare workers is not possible. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 410 patients will be randomised in 1:1 ratio to two groups: experimental group (n=205) and control group (n=205). TRIAL STATUS: Protocol version 1 was approved on 02/12/2020. Recruitment for this trial began on 02/18/2020 and will be ongoing till the required sample size is reached. The analysis deadline is August 2020. TRIAL REGISTRATION: This randomised controlled trial has been prospectively registered with the Chinese Clinical Trials (ChiCTR2000029972) on 17 February 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.” The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


title: SAMHSA provides ongoing support for MH, SUD community amid COVID‐19 pandemic

text: Observing that suicide is the 10th‐leading cause of death in this country and noting the accompanying stressors now evident as a result of the pandemic, the Substance Abuse and Mental Health Services Administration (SAMHSA) announced last week an emergency $40 million grant program to prevent suicide.


title: The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

text: A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th(,) 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).


title: Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy

text: [Image: see text] A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (∼82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M(pro)) or 3-chymotrypsin-like cysteine protease (3CL(pro)), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M(pro) is highly conserved among various CoVs, and a mutation in M(pro) is often lethal to the virus. Thus, drugs targeting the M(pro) enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M(pro) represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV M(pro) on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.


title: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations

text: The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virion’s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious.


title: Kinase inhibitor roscovitine as a PB2 cap-binding inhibitor against influenza a virus replication

text: Abstract In this study, we examined the impact of roscovitine, a cyclin-dependent kinase inhibitor (CDKI) that has entered phase I and II clinical trials, on influenza A viruses (IAVs) and its antiviral mechanism. The results illustrated that roscovitine inhibited multiple subtypes of influenza strains dose-dependently, including A/WSN/1933(H1N1), A/Aichi/2/68 (H3N2) and A/FM1/47 (H1N1) with IC50 value of 3.35 ± 0.39, 7.01 ± 1.84 and 5.99 ± 1.89 μM, respectively. Moreover, roscovitine suppressed the gene transcription and genome replication steps in the viral life cycle. Further mechanistic studies indicated that roscovitine reduced viral polymerase activity and bound specifically to the viral PB2cap protein by fluorescence polarization assay (FP) and surface plasmon resonance (SPR). Therefore, we believed roscovitine, as a PB2cap inhibitor, was a prospective antiviral agent to be developed as therapeutic treatment against influenza A virus infection.


title: Policy and Science for Global Health Security: Shaping the Course of International Health

text: The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.


title: Tissue Processing: Role of Secondary Sterilization Techniques

text: Secondary sterilization of musculoskeletal allografts may use chemicals, radiation, or combinations of these. No sterilization techniques have been definitively proven to be more effective than others, and their biomechanical and biological effects on allograft tissue remain largely unknown. The current risk of an allograft infection appears to be much less than the risk of infection surrounding the surgical procedure itself. With appropriate donor screening, improved donor testing—including nucleic acid testing (NAT), and adherence to AATB standards—the risk of disease transmission or infections can be eliminated or substantially decreased.


The prevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG antibodies in intensive care unit (ICU) healthcare personnel (HCP) and its implications—a single-center, prospective, pilot study


docid: qzrhihoz

title: Epidemiology-based Task Assignment Algorithm for Distributed Systems

text: Abstract Objective Design task assignment algorithms based on the patterns of disease spread among the population. Scope Epidemiology studies spatiotemporal patterns of illness in populations and the factors affecting it. An epidemic emerges out of the population activities and environment. Task assignment is a common activity in many realms where sub-tasks are created, delegated, and collectively carried out to achieve the original task. Due to its complexity and context, task assignment can be a challenging activity that can result in limited outcomes. This research studies task assignment as an epidemic assigned to a distributed system. We have developed computational models to understand the outbreak of aerosol-borne diseases by using the agent-based modelling approach. Experiments are carried out to observe the patterns of emergence during the spread of disease among the individuals and get insights of their mechanisms. These mechanisms are used to design algorithms for task assignment on distributed systems. Results Understanding the emergent behaviour of diseases can provide the platform for the development of distributed algorithms that can be helpful in overcoming some of the challenges of task assignment in a distributed system.


title: Molecular mechanisms and epidemiology of COVID-19 from an allergist’s perspective

text: The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold higher receptor-binding capacity compared with previous pandemic coronaviruses. In addition, because asymptomatic persons infected with SARS-CoV-2 have high viral loads in their nasal secretions, they can silently and efficiently spread the disease. PCR-based tests have emerged as the criterion standard for the diagnosis of infection. Caution must be exercised in interpreting antibody-based tests because they have not yet been validated, and may give a false sense of security of being “immune” to SARS-CoV-2. We discuss how the development of some symptoms in allergic rhinitis can serve as clues for new-onset COVID-19. There are mixed reports that asthma is a risk factor for severe COVID-19, possibly due to differences in asthma endotypes. The rapid spread of COVID-19 has focused the efforts of scientists on repurposing existing Food and Drug Administration–approved drugs that inhibit viral entry, endocytosis, genome assembly, translation, and replication. Numerous clinical trials have been launched to identify effective treatments for COVID-19. Initial data from a placebo-controlled study suggest faster time to recovery in patients on remdesivir; it is now being evaluated in additional controlled studies. As discussed in this review, till effective vaccines and treatments emerge, it is important to understand the scientific rationale of pandemic-mitigation strategies such as wearing facemasks and social distancing, and implement them.


title: First autochthonous case of clinical Hepatozoon felis infection in a domestic cat in Central Europe

text: Abstract Three different Hepatozoon (Apicomplexa, Hepatozoidae) species have been described infecting domestic cats in Europe (i.e. H. felis, H. canis and H. silvestris), however, reports on clinical hepatozoonosis are uncommon and treatment protocols are not clearly defined. A six-year-old male European short-hair cat from Austria presented poor general condition, lethargy, anorexia, icterus, a painful abdomen, fever, ruffled hair and a tick infestation, and it had never left Austria. Laboratory tests revealed leukopenia, thrombocytopenia and increased serum levels of symmetric dimethylarginine (SDMA) and bilirubin. In May Grünwald-Giemsa-stained blood smears, structures resembling Hepatozoon gamonts were observed inside neutrophil granulocytes. A PCR targeting a fragment of the 18S rRNA gene of Hepatozoon spp. and DNA sequencing allowed the diagnosis of H. felis-DNA in blood samples. The cat was treated with imidocarb dipropionate (6 mg/kg body weight, repeated after 14 days) and doxycycline monohydrate (5 mg/kg body weight twice a day, p.o., for four weeks) and recovered completely. A broad haematological and biochemical laboratory control after six months showed all evaluated parameters under normal ranges. Coinfection with other feline pathogens (i.e. feline leukaemia virus, feline immunodeficiency virus, feline Coronavirus, Leishmania and Dirofilaria immitis) could not be detected. This study reveals the presence of H. felis in Austria and provides more evidence on the geographical distribution and pathogenicity of this parasite for domestic cats. To the authors' knowledge, this is the first autochthonous case of feline hepatozoonosis in Central Europe.


docid: ilykhpgs

title: Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity

text: BACKGROUND & AIMS: The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function. METHODS: We characterized a series of cyclosporine (CsA) derivatives for their anti-HBV activity and NTCP binding specificity using HepG2 cells overexpressing NTCP and primary human hepatocytes. The four most potent derivatives were tested for their capacity to prevent HBV entry, but maintain NTCP transporter function. Their antiviral activity against different HBV genotypes was analysed. RESULTS: We identified several CsA derivatives that inhibited HBV infection with a sub-micromolar IC(50). Among them, SCY446 and SCY450 showed low activity against calcineurin (CN) and cyclophilins (CyPs), two major CsA cellular targets. This suggested that instead, these compounds interacted directly with NTCP to inhibit viral attachment to host cells, and have no immunosuppressive function. Importantly, we found that SCY450 and SCY995 did not impair the NTCP-dependent uptake of bile acids, and inhibited multiple HBV genotypes including a clinically relevant nucleoside analog-resistant HBV isolate. CONCLUSIONS: This is the first example of small molecule selective inhibition of HBV entry with no decrease in NTCP transporter activity. It suggests that the anti-HBV activity can be functionally separated from bile acid transport. These broadly active anti-HBV molecules are potential candidates for developing new drugs with fewer adverse effects. LAY SUMMARY: In this study, we identified new compounds that selectively inhibited hepatitis B virus (HBV) entry, and did not impair bile acid uptake. Our evidence offers a new strategy for developing anti-HBV drugs with fewer side effects.


The consequences of the COVID‐19 pandemic for self‐care in patients supported with a Left Ventricular Assist Device


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title: The Response in Air Quality to the Reduction of Chinese Economic Activities during the COVID‐19 Outbreak

text: During the COVID‐19 outbreak that took place in early 2020, the economic activities in China were drastically reduced and accompanied by a strong reduction in the emission of primary air pollutants. On the basis of measurements made at the monitoring stations operated by the China National Environmental Monitoring Center, we quantify the reduction in surface PM(2.5), NO(2), CO and SO(2) concentrations in northern China during the lockdown, which started on 23 January 2020. We find that, on the average, the levels of surface PM(2.5) and NO(2) have decreased by approximately 35 and 60 percent, respectively, between the period 1‐22 January 2020 and the period 23 January‐29 February 2020. At the same time, the mean ozone concentration has increased by a factor 1.5–2. In urban area of Wuhan, where drastic measures were adopted to limit the spread of the coronavirus, similar changes in the concentrations of PM(2.5), NO(2) and ozone are found.


Violence against women, children, and adolescents during the COVID-19 pandemic: overview, contributing factors, and mitigating measures.


title: Current Situation and Perspectives of Clinical Study in Integrative Medicine in China

text: Integrative medicine is not only an innovative China model in clinical practice, but also the bridge for TCM toward the world. In the past thirty years, great achievements have been made in integrative medicine researches, especially in clinical practice. The clinical achievements mainly include the following three: innovating methodology of disease-syndrome combination, excavating the classical theory in traditional Chinese medicine (TCM), preventing and curing refractory diseases. The development ideas and strategies of integrative medicine for future mainly include (a) standing on frontier field of international medicine and improving the capability of preventing and curing refractory diseases; (b) moving prevention and control strategy forward and improving the curative effect of common and frequent disease; (c) excavating the classical theory of TCM and broadening the treatment system of modern medicine; (d) improving the innovation level of new high effective drugs on the basis of classical prescriptions and herbs in TCM; (e) rerecognizing the theory of formula corresponding to syndrome in TCM and enhancing the level of clinical research evidence based on evidence-based medicine. Integrative medicine will do obtain greater achievements in creating new medicine and pharmacology and make more tremendous contributions for the great rejuvenation of the Chinese nation and human health care.


title: Psychological impact of healthcare workers in China during COVID-19 pneumonia epidemic: a multi-center cross-sectional survey investigation

text: BACKGROUND: : Since the outbreak of 2019 new coronavirus (COVID-19) pneumonia, healthcare workers (HCW) have suffered psychological stress. The present study is to examine the prevalence of stress, anxiety and depression of HCW in China during the COVID-19 epidemic, and to determine the risk factors predicting psychological morbidities that can be used as psychological intervention targets. METHODS: : A cross-sectional survey was conducted to investigate the psychological levels of HCW in multiple centers in China. The prevalence of stress, anxiety and depression were determined by using Perceived Stress Scale (PSS-14) and Hospital Anxiety / Depression scale (HAD). Psychology related factors were evaluated and correlation between job title and contact history was analyzed. RESULTS: : We received 958 of effective responses, 73.6% of which were from Wuhan and 67.2% were female participants. 55.1% of respondents had psychological stress that is higher than that of HCW during SARS. 54.2% and 58% of participants had symptoms of anxiety and depression. Stress levels of HCW were different in job titles and years of work experience. Anxiety and depression levels were different between different gender, job titles, degrees of protective measures and levels of contact history. Gender, intermediate title, protective measures and contact history were the independent risk factors for anxiety. Protective measures and contact history were the independent risk factors for depression. CONCLUSIONS: : The COVID-19 epidemic has induced stress levels for HCW, and high percentages of HCW have anxiety and depression. The situation of HCW is worrying and intervention service is urgent.


title: Unpacking the black box: How to promote citizen engagement through government social media during the COVID-19 crisis

text: Abstract During times of public crises, governments must act swiftly to communicate crisis information effectively and efficiently to members of the public; failure to do so will inevitably lead citizens to become fearful, uncertain and anxious in the prevailing conditions. This pioneering study systematically investigates how Chinese central government agencies used social media to promote citizen engagement during the COVID-19 crisis. Using data scraped from ‘Healthy China’, an official Sina Weibo account of the National Health Commission of China, we examine how citizen engagement relates to a series of theoretically relevant factors, including media richness, dialogic loop, content type and emotional valence. Results show that media richness negatively predicts citizen engagement through government social media, but dialogic loop facilitates engagement. Information relating to the latest news about the crisis and the government's handling of the event positively affects citizen engagement through government social media. Importantly, all relationships were contingent upon the emotional valence of each Weibo post.


title: Orthopedic healthcare in the time of COVID-19: Experience of the orthopedic surgery department at Mustapha Bacha Hospital, Algeria

text: In response to the global health emergency, which has been raised to its highest level as a consequence of the coronavirus disease 2019 (COVID-19), urgent and aggressive actions were taken by health institutions across the world to stop the spread of the disease while ensuring continuity of vital care. This article outlines the urgent measures put in place by the orthopedic surgery department at Mustapha Bacha Hospital in response to the COVID-19 pandemic.


docid: jxxcvbna

title: The Potential Impacts of Pandemic Policing on Police Legitimacy: Planning Past the COVID-19 Crisis

text: One of the biggest challenges facing modern policing in recent years has been the lack of police legitimacy. The tipping point of this phenomenon is often attributed to the Rodney King incident in Los Angeles in 1991, where Los Angeles Police Department (LAPD) officers were videoed assaulting a lone black male. They were arrested and charged but eventually all were acquitted, thereby etching deep distrust between communities and police. Now the Rodney King example is an extreme and criminal act by police but it was the beginning of communities and media focusing on what the police were doing and how they were doing it. This lack of legitimacy coupled with what is referred to as the militarization of policing have lasting consequences and impacts on police–community relations and how interactions between police and community shape society today. In the wake of pandemic policing due to COVID-19, there are tales of two eventualities for police legitimacy that will be explored in this article: (1) The police response to the pandemic results in further militarization and draws deeper divides between police and communities or (2) the police response is compassionate and build on procedurally just operations resulting in the rebuilding of police legitimacy post-pandemic.