title: Host-adapted Cryptosporidium and Enterocytozoon bieneusi genotypes in straw-colored fruit bats in Nigeria

text: Few data are available on the distribution and human infective potential of Cryptosporidium and Enterocytozoon bieneusi genotypes in bats. In this preliminary study, we collected 109 fecal specimens during April–July 2011 from a colony of straw-colored fruit bats (Eidolon helvum) in an urban park (Agodi Gardens) of Ibadan, Nigeria, and analyzed for Cryptosporidium spp., Giardia duodenalis and E. bieneusi using PCR targeting the small subunit rRNA gene, triosephosphate isomerase gene, and ribosomal internal transcribed spacer, respectively. Genotypes of these enteric parasites were determined by DNA sequencing of the PCR products. Altogether, 6 (5.5%), 0 and 16 (14.7%) specimens were positive for Cryptosporidium spp., G. duodenalis, and E. bieneusi, respectively. DNA sequence analysis of the PCR products indicated the presence of two novel Cryptosporidium genotypes named as bat genotype XIV (in 5 specimens) and bat genotype XV (in 1 specimen) and one known E. bieneusi genotype (Type IV in 1 specimen) and two novel E. bieneusi genotypes (Bat1 in 13 specimens and Bat2 in 2 specimens). In phylogenetic analysis of DNA sequences, the two novel Cryptosporidium genotypes were genetically related to Bat genotype II previously identified in fruit bats in China and Philippines, whereas the two novel E. bieneusi genotypes were genetically related to Group 5, which contains several known genotypes from primates. With the exception of Type IV, none of the Cryptosporidium and E. bieneusi genotypes found in bats in this study are known human pathogens. Thus, straw-colored fruit bats in Nigeria are mainly infected with host-adapted Cryptosporidium and E. bieneusi genotypes.


title: Transmissibility of MERS-CoV Infection in Closed Setting, Riyadh, Saudi Arabia, 2015

text: To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015–January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%–32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.


title: A critical review on serine protease: Key immune manipulator and pathology mediator

text: Proteolytic activity is fundamental to survival, so it is not surprising that all living organisms have proteases, especially seine protease. This enzyme in its numerous isoforms and homologues, constitutes the quintessential offence and defence factors, in the form of surface proteins, secreted molecules, gut digestive enzymes, venom in specialised glands or plant latex, among other manifestations. Occurring as trypsin, chymotrypsin, elastase, collagenase, thrombin, subtilisin etc., it mediates a diverse array of functions, including pathological roles as inflammatory, coagulatory to haemorrhagic. This review emphasizes that despite the superficial differences in mechanisms, most health issues, be they infectious, allergic, metabolic, or neural have a common conduit. This enzyme, in its various glycosylated forms leads to signal misinterpretations, wreaking havoc. However, organisms are endowed with serine protease inhibitors which might restrain this ubiquitous yet deleterious enzyme. Hence, serine proteases-driven pathogenesis and antagonising role of inhibitors is the focal point of this critical review.


COVID-19 and migrant workers: lack of data and need for specific management


docid: vwhbvezp

title: Porcine Deltacoronavirus Infection and Transmission in Poultry, United States

text: Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in leopard cats in China. In 2009, porcine deltacoronavirus (PDCoV) was detected in fecal samples from pigs in Asia, but its etiologic role was not identified until 2014, when it caused major diarrhea outbreaks in swine in the United States. Studies have shown that PDCoV uses a conserved region of the aminopeptidase N protein to infect cell lines derived from multiple species, including humans, pigs, and chickens. Because PDCoV is a potential zoonotic pathogen, investigations of its prevalence in humans and its contribution to human disease continue. We report experimental PDCoV infection and subsequent transmission among poultry. In PDCoV-inoculated chicks and turkey poults, we observed diarrhea, persistent viral RNA titers from cloacal and tracheal samples, PDCoV-specific serum IgY antibody responses, and antigen-positive cells from intestines.


title: Acute pulmonary embolism in COVID-19 related hypercoagulability

text: Since December 2019, a novel Coronavirus (SARS-CoV-2) was confirmed as the etiologic agent of a worldwide outbreak of a pneumonia that can result in severe respiratory failure. This clinical entity seems to be associated with a marked hypercoagulable state that causes both arterial and venous thromboembolic complications. Therefore, an adequate anti-thrombotic prophylaxis is recommended in hospitalized COVID-19 patients. Although rapidly worsening respiratory symptoms in a patient with SARS-CoV-2 respiratory infection may correlate with worsening pneumonia itself, it may also mask a pulmonary embolism. We report the case of a 50-year-old man affected by SARS-CoV-2 pneumonia, who developed acute pulmonary embolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02160-1) contains supplementary material, which is available to authorized users.


title: Arthritis suppression by NADPH activation operates through an interferon-β pathway

text: BACKGROUND: A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, neutrophil cytosolic factor 1 (NCF1), has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA). We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. RESULTS: Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-γ regulated the pathway associated with arthritis development, whereas IFN-β regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA) rat, (with an Ncf-1(DA )allele that allows only low oxidative burst), and the arthritis-protected DA.Ncf-1(E3 )rat (with an Ncf1(E3 )allele that allows a stronger oxidative burst). CONCLUSION: Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that enhances oxidative burst and protects against arthritis is operating through an IFN-β-associated pathway, whereas the arthritis-driving allele operates through an IFN-γ-associated pathway. Treatment of arthritis-susceptible rats with an NADPH oxidase-activating substance, phytol, protects against arthritis. Interestingly, the treatment led to a restoration of the oxidative-burst effect and induction of a strikingly similar IFN-β-dependent pathway, as seen with the disease-protective Ncf1 polymorphism.


title: Characterization of a recombinant canine coronavirus with a distinct receptor-binding (S1) domain

text: Abstract Canine alphacoronaviruses (CCoV) exist in two serotypes, type I and II, both of which can cause severe gastroenteritis. Here, we characterize a canine alphacoronavirus, designated CCoV-A76, first isolated in 1976. Serological studies show that CCoV-A76 is distinct from other CCoVs, such as the prototype CCoV-1-71. Efficient replication of CCoV-A76 is restricted to canine cell lines, in contrast to the prototypical type II strain CCoV-1-71 that more efficiently replicates in feline cells. CCoV-A76 can use canine aminopeptidase N (cAPN) receptor for infection of cells, but was unable to use feline APN (fAPN). In contrast, CCoV-1-71 can utilize both. Genomic analysis shows that CCoV-A76 possesses a distinct spike, which is the result of a recombination between type I and type II CCoV, that occurred between the N- and C-terminal domains (NTD and C-domain) of the S1 subunit. These data suggest that CCoV-A76 represents a recombinant coronavirus form, with distinct host cell tropism.


Nursing Activities Score is increased in COVID-19 patients : comments


Web surveys in the time of COVID-19


title: Treatment and vaccines for severe acute respiratory syndrome

text: Summary The causative agent of severe acute respiratory syndrome (SARS), which affected over 8000 individuals worldwide and was responsible for over 700 deaths in the 2002–2003 outbreak, is a coronavirus that was unknown before the outbreak. Although many different treatments were used during the outbreak, none were implemented in a controlled fashion. Thus, the optimal treatment for SARS is unknown. Since the outbreak, much work has been done testing new agents against SARS using in-vitro methods and animal models. In addition, global research efforts have focused on the development of vaccines against SARS. Efforts should be made to evaluate the most promising treatments and vaccines in controlled clinical trials, should another SARS outbreak occur.


title: The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

text: Abstract This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. As with the first paper, rather than providing a chronological account, we have chosen to examine particular examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics. The first review covered the more common, and in most cases, single modifications to the sugar and base moieties of the nucleoside scaffold. This paper focuses on more recent developments, especially nucleoside analogues that contain more than one modification to the nucleoside scaffold. We hope that these two articles will provide an informative historical perspective of some of the successfully designed analogues, as well as many candidate compounds that encountered obstacles.


title: Improvement of different vaccine delivery systems for cancer therapy

text: Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.


title: Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome Patients Quarantined in Hospital: A Retrospective Chart Analysis

text: OBJECTIVE: Little is known about the psychiatric complications or risk factors for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS) patients quarantined in hospital. METHODS: A retrospective chart review was performed of all the patients admitted to the acute MERS inpatient unit at the NMC during the 2015 outbreak. RESULTS: 30 (75%) were confirmed to be MERS-CoV positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%) exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis and medication during their hospital stay. Suspected MERS patients did not exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or confirmed MERS patients (age 41.15±18.64, male 37.0%) completed psychological assessments. A multiple linear regression analysis revealed that the Korean National Health and Nutrition Examination Survey-Short form and the Impact of Event Scale-Revised scores were significantly positively correlated with Patient Health Questionnaire-9 scores. CONCLUSION: Our findings indicate that the acute treatment of MERS-CoV infections in quarantine had a significant impact on the patients’ mental health. Furthermore, assessment of the risk factors for depression may identify vulnerable patients who require psychiatric care and attention during hospital quarantine.


2019 Novel coronavirus and awareness


title: Design of a set of probes with high potential for influenza virus epidemiological surveillance

text: An Influenza Probe Set (IPS) consisting in 1,249 9-mer probes for genomic fingerprinting of closely and distantly related Influenza Virus strains was designed and tested in silico. The IPS was derived from alignments of Influenza genomes. The RNA segments of 5,133 influenza strains having diverse degree of relatedness were concatenated and aligned. After alignment, 9-mer sites having high Shannon entropy were searched. Additional criteria such as: G+C content between 35 to 65%, absence of dimer or trimer consecutive repeats, a minimum of 2 differences between 9mers and selecting only sequences with Tm values between 34.5 and 36.5oC were applied for selecting probes with high sequential entropy. Virtual Hybridization was used to predict Genomic Fingerprints to assess the capability of the IPS to discriminate between influenza and related strains. Distance scores between pairs of Influenza Genomic Fingerprints were calculated, and used for estimating Taxonomic Trees. Visual examination of both Genomic Fingerprints and Taxonomic Trees suggest that the IPS is able to discriminate between distant and closely related Influenza strains. It is proposed that the IPS can be used to investigate, by virtual or experimental hybridization, any new, and potentially virulent, strain.


title: Reversible Unfolding of the Severe Acute Respiratory Syndrome Coronavirus Main Protease in Guanidinium Chloride

text: Chemical denaturant sensitivity of the dimeric main protease from severe acute respiratory syndrome (SARS) coronavirus to guanidinium chloride was examined in terms of fluorescence spectroscopy, circular dichroism, analytical ultracentrifuge, and enzyme activity change. The dimeric enzyme dissociated at guanidinium chloride concentration of <0.4 M, at which the enzymatic activity loss showed close correlation with the subunit dissociation. Further increase in guanidinium chloride induced a reversible biphasic unfolding of the enzyme. The unfolding of the C-terminal domain-truncated enzyme, on the other hand, followed a monophasic unfolding curve. Different mutants of the full-length protease (W31 and W207/W218), with tryptophanyl residue(s) mutated to phenylalanine at the C-terminal or N-terminal domain, respectively, were constructed. Unfolding curves of these mutants were monophasic but corresponded to the first and second phases of the protease, respectively. The unfolding intermediate of the protease thus represented a folded C-terminal domain but an unfolded N-terminal domain, which is enzymatically inactive due to loss of regulatory properties. The various enzyme forms were characterized in terms of hydrophobicity and size-and-shape distributions. We provide direct evidence for the functional role of C-terminal domain in stabilization of the catalytic N-terminal domain of SARS coronavirus main protease.


Keeping up with the fast-moving world of crisis management


title: Phylogeny and biogeography of western Indian Ocean Rousettus (Chiroptera: Pteropodidae)

text: We examined patterns of genetic variation in Rousettus madagascariensis from Madagascar and R. obliviosus from the Comoros (Grande Comore, Anjouan, and Mohéli). Genetic distances among individuals on the basis of 1,130 base pairs of the mitochondrial cytochrome b (Cytb) locus were estimated from specimens collected from 17 sites on Madagascar, 3 sites on Grande Comore, 3 sites on Anjouan, and 2 sites on Mohéli. We observed little variation in Madagascar and nearshore island samples (maximum 1.1%) and interisland Comoros samples (maximum 1.8%). In contrast, pairwise distances between different sampled sites on Madagascar and the Comoros varied from 8.5% to 13.2%. For 131 Malagasy animals, 69 unique haplotypes were recovered with 86 variable sites, and for 44 Comorian individuals, 17 unique haplotypes were found with 30 variable sites. No haplotype was shared between Madagascar and the Comoros, adding to previous morphological evidence that these 2 populations should be considered separate species. Cytb data showed that Rousettus populations of Madagascar (including nearshore islands) and the Comoros are respectively monophyletic and display no geographic structure in haplotype diversity, and that R. madagascariensis and R. obliviosus are strongly supported as sister to each other relative to other Rousettus species. Genotypic data from 6 microsatellite loci confirm lack of geographic structure in either of the 2 species. In pairwise tests of population differentiation, the only significant values were between samples from the Comoro Islands and Madagascar (including nearshore islands). Estimates of current and historical demographic parameters support population expansion in both the Comoros and Madagascar. These data suggest a more recent and rapid demographic expansion in Madagascar in comparison with greater population stability on the Comoros. On the basis of available evidence, open-water crossings approaching 300 km seem rarely traversed by Rousettus, and, if successful, can result in genetic isolation and subsequent differentiation.


docid: wwiopinv

title: Chapter 25 Preclinical Toxicology of Vaccines 1

text: Immunity to targeted infectious diseases may be conferred or enhanced by vaccines, which are manufactured from recombinant forms as well as inactivated or attenuated organisms. These vaccines have to meet requirements for safety, quality and efficacy. In addition to antigenic components, various adjuvants may be included in vaccines to evoke an effective immune response. To ensure the safety of new vaccines, preclinical toxicology studies are conducted prior to the initiation of, and concurrently with, clinical studies. There are five different types of preclinical toxicology study in the evaluation of vaccine safety: single and/or repeat dose, reproductive and developmental, mutagenicity, carcinogenicity, and safety pharmacology. If any adverse effects are observed in the course of these studies, they should be fully evaluated and a final safety decision made accordingly. Successful preclinical toxicology studies depend on multiple factors including: using the appropriate study designs, using the right animal model, and evoking an effective immune response. Additional in vivo and in vitro assays that establish the identity, purity, safety, and potency of the vaccine play a significant role in assessing critical characteristics of vaccine safety.


title: Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

text: Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The first(t) of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects.


title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

text: Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.


Effectiveness of a ‘fast lung ultrasound teaching program’ for gynecologists/obstetricians dealing with pregnant women with suspicion of COVID‐19 infection


title: Genotype and phenotype of COVID-19: Their roles in pathogenesis

text: Abstract COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3′-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.


docid: kwytbqoy

title: Hospitalización por Insuficiencia Cardíaca durante la pandemia de COVID-19


title: The moonlighting enzyme CD13: old and new functions to target

text: Aminopeptidase N (CD13) is a widely expressed ectoenzyme with functions that do not always depend on its enzymatic activity: an aspect that has been overlooked. Numerous CD13-targeting tools have been developed in the last few years. Several of them are already undergoing clinical trials, and there are promising reports on the effectiveness of others in animal models of disease. However, their efficacy might be obscured by their effects on unrecognized functions of CD13, resulting in unexpected complications. The purpose of this review is (i) to discuss the various functions ascribed to CD13 and the possible mechanisms behind them and (ii) to consider some of the questions that need to be answered to achieve a better understanding of the biological relevance of these functions, a more precise interpretation of the results obtained after their manipulation and a more rational design of CD13-targeting agents.


title: Investigating the dynamics of COVID-19 pandemic in India under lockdown

text: In this paper, we investigate the ongoing dynamics of COVID-19 in India after its emergence in Wuhan, China in December 2019. We discuss the effect of nationwide lockdown implemented in India on March 25, 2020 to prevent the spread of COVID-19. Susceptible-Exposed-Infectious-Recovered (SEIR) model is used to forecast active COVID-19 cases in India considering the effect of nationwide lockdown and possible inflation in the active cases after its removal on May 3, 2020. Our model predicts that with the ongoing lockdown, the peak of active infected cases around 43,000 will occur in the mid of May, 2020. We also predict a 7 to 21% increase in the peak value of active infected cases for a variety of hypothetical scenarios reflecting a relative relaxation in the control strategies implemented by the government in the post-lockdown period. For India, it is an important decision to come up with a non-pharmaceutical control strategy such as nationwide lockdown for 40 days to prolong the higher phases of COVID-19 and to avoid severe load on its public health-care system. As the ongoing COVID-19 outbreak remains a global threat, it is a challenge for all the countries to come up with effective public health and administrative strategies to battle against COVID-19 and sustain their economies.


title: Viral Pneumonias Other Than Cytomegalovirus in Transplant Recipients

text: Community-acquired respiratory viruses (CARVs) are frequent causes of upper and lower respiratory tract infections in tranplant recipients. In most series, respiratory syncytial virus and parainfluenza are the most common CARVs, followed by influenza and adenovirus. Significant morbidity and mortality are associated with these infections, particularly when they progress to pneumonia or when they are associated with bacterial or fungal coinfections. Outcomes are also poor with adenovirus, frequently reflecting disseminated infection. Efforts to prevent morbidity and mortality from CARV infection should focus on prevention, because treatment options are limited with inconclusive data to support their efficacy.


title: Analysis of protein expression by mammalian cell lines stably expressing lactate dehydrogenase-elevating virus ORF 5 and ORF 6 proteins

text: Abstract Lactate dehydrogenase-elevating virus (LDV) has a strict species-specificity. Because only a subset of mouse primary macrophages have been identified that can support LDV replication in vitro, the precise molecular mechanism of viral entry and replication remains unclear. To analyze the LDV envelope proteins, which probably mediate viral attachment to the host cell, we developed a mammalian system for stable co-expression of LDV open reading frame (ORF) 5- and ORF 6-encoded proteins (ORF 5 and ORF 6 proteins), which correspond to envelope VP-3 and M/VP-2, respectively, and compared these expressed proteins to the native ones. Western blotting analysis combined with N-glycanase digestion revealed that ORF 5 and ORF 6 proteins were similar in size to native VP-3 and M/VP-2, and that ORF 5 protein was N-glycosylated, like the native VP-3. Immunofluorescence microscopy revealed that both ORF 5 and ORF 6 proteins were distributed throughout the cytoplasm and were colocalized in most cells. Moreover, ORF 5 protein was localized both in the perinuclear region and the Golgi complex and transported to the cell surface. This mammalian expression system in which the exogenously expressed proteins closely resemble the native proteins will provide the experimental basis for further studies of the interactions between LDV envelope proteins and host cells.


Disease eradication is possible and ethical


title: Federated or cached searches: Providing expected performance from multiple invasive species databases

text: Invasive species are a universal global problem, but the information to identify them, manage them, and prevent invasions is stored around the globe in a variety of formats. The Global Invasive Species Information Network is a consortium of organizations working toward providing seamless access to these disparate databases via the Internet. A distributed network of databases can be created using the Internet and a standard web service protocol. There are two options to provide this integration. First, federated searches are being proposed to allow users to search “deep” web documents such as databases for invasive species. A second method is to create a cache of data from the databases for searching. We compare these two methods, and show that federated searches will not provide the performance and flexibility required from users and a central cache of the datum are required to improve performance.


title: Genome and Bioinformatic Analysis of a HAdV-B14p1 Virus Isolated from a Baby with Pneumonia in Beijing, China

text: The genome of HAdV-B14p1 strain BJ430, isolated from a six-month-old baby diagnosed with bronchial pneumonia at the Beijing Children’s Hospital in December 2010, was sequenced, analyzed, and compared with reference adenovirus genome sequences archived in GenBank. This genome is 34,762 bp in length, remarkably presenting 99.9% identity with the genome from HAdV14p1 strain 303600, which was isolated in the USA (2006). Even more remarkable, it is 99.7% identical with the HAdV-B14p (prototype “de Wit” strain) genome, isolated from The Netherlands in 1955. The patient and its parents presumably had no or limited contact with persons from the USA and Ireland, both of which reported outbreaks of the re-emergent virus HAdV-14p1 recently. These genome data, its analysis, and this report provide a reference for any additional HAdV-B14 outbreak in China and provide the basis for the development of adenovirus vaccines and molecular pathogen surveillance protocols in high-risk areas.


title: IJED support for eating disorders research in the time of COVID‐19

text: This editorial reports on an anonymous survey question posed to eating disorders researchers about changes the International Journal of Eating Disorders (IJED) should implement to support the eating disorders research community affected by COVID‐19. The editorial accompanies an IJED article that details responses to the larger survey focusing more broadly on COVID‐19‐related research disruptions. Survey invitations were sent to editorial board members of eating disorders journals, members of eating disorder scientific organizations (e.g., Eating Disorders Research Society), and individuals who provided at least three IJED reviews in the prior 12 months. We reviewed the responses of 187 participants and identified three categories of changes that: (a) had already been implemented by the journal, (b) cannot be implemented because they fall outside the scope of IJED, or (c) will be implemented in coming weeks or months. The latter category includes publishing topical COVID‐19 papers, making some COVID‐19‐related content available open access, revising statistical guidelines, and issuing author guidance on reporting protocol changes caused by COVID‐19‐related disruptions. IJED recognizes the disruptive impacts that COVID‐19 has on all activities in our field, including clinical work, teaching, and advocacy, and is committed to supporting authors during this difficult time while striving to publish high‐quality research.


title: Optimistic bias, information seeking and intention to undergo prostate cancer screening: A Taiwan study on male adults

text: Abstract Background This study explores optimistic bias and information seeking in prostate cancer patients and how they impact intention to undergo prostate cancer screening. Methods A national sample of 427 Taiwanese male adults aged at least 45 years (mean (M)=57) were recruited to complete a telephone-based survey questionnaire between April 30 and May 8, 2008. Results The questionnaire results showed that respondents considered themselves less likely than others to get prostate cancer. The relationship between optimistic bias and intention to undergo prostate cancer screening was non-significant, while information seeking positively and significantly predicted such an intention. Conclusions The findings of this study imply that health educators should include risk-awareness strategies and information seeking interventions in the design of cancer prevention programs.


title: Burden, seasonal pattern and symptomatology of acute respiratory illnesses with different viral aetiologies in children presenting at outpatient clinics in Hong Kong

text: Abstract Respiratory viruses cause acute respiratory diseases with a broad and overlapping spectrum of symptoms. We examined the clinical symptoms and explored the patterns of various respiratory viral infections in children in Hong Kong. Among 2090 specimens collected from outpatient care (2007–2010), 1343 (64.3%) were positive for any virus by the xTAG assay, and 81 (3.9%) were positive for co-infection. The most frequently detected viruses among children aged 6–15 years were enterovirus/rhinovirus and influenza virus A, whereas most non-influenza viruses were more frequently detected in younger children. Higher body temperature was more common for illnesses associated with influenza viruses than for those associated with non-influenza viruses, but other symptoms were largely similar across all infections. The seasonality pattern varied among different viruses, with influenza virus A being the predominant virus detected in winter, and enterovirus/rhinovirus being more commonly detected than influenza virus A in the other three seasons, except for 2009.


title: Social Consequences of Ebola Containment Measures in Liberia

text: INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. Enforced by State-related actors, these were promoted as the only method to curtail transmissions as soon as possible. However, as with other harsh measures witnessed by Liberian citizens, in many cases those measures elicited uncontrolled negative reactions within the communities (stigma; fear) that produced, in some cases, the opposite effect of that intended. METHODOLOGY: The research has been conducted in two phases, for a total of 8 weeks. Ethnography of local practices was carried out in 7 neighbourhoods in Monrovia and 5 villages in Grand Cape Mount County in Liberia. 45 Focus Group Discussions (432 participants) and 30 semi-structured interviews sustained the observing participation. Randomly selected people from different social layers were targeted. The principal investigator worked with the help of two local assistants. Perceptions and practices were both analysed. RESULTS: Participants stressed how cremation perpetuated the social breakdown that started with the isolation for the sickness. Socio-economical divides were created by inequitable management of the dead: those who could bribe the burial teams obtained a burial in a private cemetery or the use of Funeral Homes. Conversely, those in economic disadvantage were forced to send their dead for cremation. State-enforced quarantine, with a mandatory prohibition of movement, raised condemnation, strengthened stigmatization and created serious socio-economic distress. Food was distributed intermittently and some houses shared latrines with non-quarantined neighbours. Escapes were also recorded. Study participants narrated how they adopted local measures of containment, through local task forces and socially-rooted control of outsiders. They also stressed how information that was not spread built up rumours and suspicion. CONCLUSIONS: Populations experiencing an epidemic feel a high degree of social insecurity, in addition to the health hazards. Vertical and coercive measures increase mistrust and fear, producing a counter-productive effect in the containment of the epidemic. On the other hand, local communities show a will to be engaged and a high degree of flexibility in participating to the epidemic response. Efforts in the direction of awareness and community involvement could prove to be better strategy to control the epidemic and root the response on social participation.


title: Interplay between the cellular autophagy machinery and positive-stranded RNA viruses

text: Autophagy is a conserved cellular process that acts as a key regulator in maintaining cellular homeostasis. Recent studies implicate an important role for autophagy in infection and immunity by removing invading pathogens and through modulating innate and adaptive immune responses. However, several pathogens, notably some positive-stranded RNA viruses, have subverted autophagy to their own ends. In this review, we summarize the current understanding of how viruses with a positive-stranded RNA genome interact with the host autophagy machinery to control their replication and spread. We review the mechanisms underlying the induction of autophagy and discuss the pro- and anti-viral functions of autophagy and the potential mechanisms involved.


title: Cognitive-behavioral group program for Chinese heterosexual HIV-infected men in Hong Kong

text: Abstract This study explored the effects of cognitive-behavioral program (CBP) using a wait-list control group in 16 Chinese heterosexual HIV-infected men. Participants in the treatment condition underwent a 7-week group based CBP, which addressed various HIV-related issues. Relevant cognitive and behavioral strategies were taught as well. The aim of treatment was to improve the quality of life and to reduce psychological distress in a sample of heterosexual symptomatic HIV-infected men. Prior to intervention, baseline measures showed that our sample had a lower quality of life in comparison with the local general population. They also experienced a significant level of psychological distress. Following intervention, men in the CBP group demonstrated significant improvement in the mental health dimension of quality of life and a significant reduction in depressed mood. These preliminary findings suggested that short-term cognitive-behavioral therapy can be effective in improving the quality of life and mood of Chinese heterosexual HIV-infected men.


title: Establishment and evaluation of a theater influenza monitoring platform

text: BACKGROUND: Influenza is an acute respiratory infectious disease with a high incidence rate in the Chinese army, which directly disturbs military training and affects soldiers’ health. Influenza surveillance systems are widely used around the world and play an important role in influenza epidemic prevention and control. METHODS: As a theater centers for disease prevention and control, we established an influenza monitoring platform (IMP) in 2014 to strengthen the monitoring of influenza-like illness and influenza virus infection. In this study, we introduced the constitution, influenza virus detection, and quality control for an IMP. The monitoring effect was also evaluated by comparing the monitoring data with data from national influenza surveillance systems. The experiences and problems associated with the platform also were summarized. RESULTS: A theater IMP was established based on 3 levels of medical units, including monitoring sites, testing laboratories and a checking laboratory. A series of measures were taken to guarantee the quality of monitoring, such as technical training, a unified process, sufficient supervision and timely communication. The platform has run smoothly for 3 monitoring years to date. In the 2014–2015 and 2016–2017 monitoring years, sample amount coincided with that obtained from the National Influenza Surveillance program. In the 2015–2016 monitoring year, due to the strict prevention and control measures, an influenza epidemic peak was avoided in monitoring units, and the monitoring data did not coincide with that of the National Influenza Surveillance program. Several problems, including insufficient attention, unreasonable administrative intervention or subordination relationships, and the necessity of detection in monitoring sites were still observed. CONCLUSIONS: A theater IMP was established rationally and played a deserved role in the prevention and control of influenza. However, several problems remain to be solved.


title: Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections

text: Summary Three years after its first discovery in Jeddah Saudi Arabia, the novel zoonotic pathogen of humans, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a major threat to global health security. 1 Sporadic community acquired cases of MERS continue to be reported from the Middle East. The recent nosocomial outbreaks in hospitals in Seoul, Korea and at the National Guard Hospital in Riyadh, Saudi Arabia indicate the epidemic potential of MERS-CoV. Currently there are no effective anti-MERS-CoV anti-viral agents or therapeutics and MERS is associated with a high mortality rate (40%) in hospitalised patients. A large proportion of MERS patients who die have a range of pulmonary pathology ranging from pneumonia to adult respiratory distress syndrome with multi-organ failure, compounded by co-morbidities, reflecting a precarious balance of interactions between the host-immune system and MERS-CoV. Whilst we wait for new MERS-CoV specific drugs, therapeutics and vaccines to be developed, there is a need to advance a range of Host-Directed Therapies. A range of HDTs are available, including commonly used drugs with good safety profiles, which could augment host innate and adaptive immune mechanisms to MERS-CoV, modulate excessive inflammation and reduce lung tissue destruction. We discuss the rationale and potential of using Host-Directed Therapies for improving the poor treatment outcomes associated with MERS. Carefully designed randomized controlled trials will be needed to determine whether HDTs could benefit patients with MERS. The recurrent outbreaks of MERS-CoV infections at hospitals in the Middle East present unique opportunities to conduct randomized clinical trials. The time has come for a more coordinated global response to MERS and a multidisciplinary global MERS-CoV response group is required to take forward priority research agendas.


title: Tackling the COVID-19 Pandemic

text: Abstract After the initial breakout of the SARS-CoV-2 epidemic (now called COVID-19)—in Wuhan, China—and its subsequent fast dispersion throughout the world, many questions regarding its pathogenesis, genetic evolution, prevention, and transmission routes remain unanswered but fast explored. More than 100,000 confirmed, infected cases within a relatively short period of time globally corroborated the presumption that a pandemic will develop; such a pandemic will require a suite of global intervention measures. Consequently, different countries have reacted differently to the COVID-19 outbreak, but a uniform global response is necessary for tackling the pandemic. Managing the present or future COVID-19 outbreaks is not impossible but surely difficult. Barring the live-animal trade at the markets; revising the regulations and rules of customs, import or export across borders; supporting and expediting projects to develop vaccines and antiviral drugs; immediate quarantine of the involved regions; and also producing and supplying a large number of protective facemasks and preventing its stockpiling or smuggling are the main actions suggested to deal with the present or a forthcoming COVID-19 outbreak. Increasing numbers of infected cases had heightened concerns about the public health and welfare. Thus, preparing for the next probable pandemic of COVID-19 demands scrutinization of the lessons we have learnt so far.


title: Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy

text: A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease, treatment decisions, and assessing drug efficacy. This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging. Pooled plasma from different liver fibrosis stages, which were assessed in advance by the current gold-standard of liver biopsy, was quantitatively analyzed. A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process, and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis. Validation results of fibronectin by Western blotting reconfirmed the mass-based data. Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients. Consequently, quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis. We quantitatively monitored the fibrogenesis process in CHB patients. We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease. These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-011-4165-y and is accessible for authorized users.


The effects of glass surfaces and probe GC content on signal intensities of a 60-mer diagnostic microarray were studied. Twelve virus-specific oligonucleotide probes for severe acute respiratory syndrome coronavirus (SARS-CoV) were divided into a high GC content group (≥ 50%) and a low GC content group (< 50%), and spotted onto four different chemically-modified glass surfaces: a poly-amine coating activated by 1,4-phenylene diisothiocyanate (Poly-Amine surface), an acrylic acid-co-acrylamide copolymer coating activated by 1-(3-dimethylamino propyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (AACA-Copolymer surface), a commercial Corning CMT-GAPS amino surface, and a Telechem SuperAmine amino surface. RNA samples from cultured SARS-CoV strain were labelled using direct cDNA labelling with restriction display in a single colour format. The background-subtracted signal intensities were analysed using two-way analysis of variance. The effects of glass surfaces on background-subtracted signal intensities were significant (p=0.003). Multiple comparisons showed that differences existed mainly between the AACA-Copolymer surface and the other glass surfaces, and that the AACA-Copolymer surface had the highest background-subtracted signal intensity. The probe GC content had no significant effect on signal intensities in the narrow range of GC content represented (p=0.07). The results suggested that the AACA-Copolymer surface may be a novel choice of microorganism survey based on long oligonucleotide microarray.


title: DNA-based bioanalytical microsystems for handheld device applications

text: Abstract This article reviews and highlights the current development of DNA-based bioanalytical microsystems for point-of-care diagnostics and on-site monitoring of food and water. Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. Product detection approaches utilizing “portable” detection signals and electrochemistry-based methods are emphasized in this work. The strategies and challenges for the integration of individual processing module on the same chip are discussed.


title: Photochemistry and pharmacology of 9, 19-cyclolanostane glycosides isolated from genus Cimicifuga

text: Abstract The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9, 19-cyclolanostane triterpenoid glycosides, which often exhibit extensive pharmacological activities. 9, 19-Cyclolanostane triterpenoid glycosides are distributed widely in genus Cimicifuga rather than in other members of the Ranunculaceae family. So far, more than 140 cycloartane triterpene glycosides have been isolated from Cimicifuga spp.. The aim of this review was to summarize all 9, 19-cyclolanostane triterpenoid glycosides based on the available relevant scientific literatures from 2000 to 2014. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.


title: Cluster of Human Infections with Avian Influenza A (H7N9) Cases: A Temporal and Spatial Analysis

text: Objectives: This study aims to describe the spatial and temporal characteristics of human infections with H7N9 virus in China using data from February 2013 to March 2014 from the websites of every province’s Population and Family Planning Commission. Methods: A human infection with H7N9 virus dataset was summarized by county to analyze its spatial clustering, and by date of illness onset to analyze its space-time clustering using the ESRI(®) Geographic Information System (GIS) software ArcMap™ 10.1 and SatScan. Results: Based on active surveillance data, the distribution map of H7N9 cases shows that compared to the rest of China, the areas from near the Yangtze River delta (YRD) to farther south around the Pearl River delta (PRD) had the highest densities of H7N9 cases. The case data shows a strong space-time clustering in the areas on and near the YRD from 26 March to 18 April 2013 and a weak space-time clustering only in the areas on and near the PRD between 3 and 4 February 2014. However, for the rest of the study period, H7N9 cases were spatial-temporally randomly distributed. Conclusions: Our results suggested that the spatial-temporal clustering of H7N9 in China between 2013 and 2014 is fundamentally different.


title: Identify driving forces of MBR applications in China

text: Abstract During the last two decades, MBR applications in China grow exponentially with the first pilot test of 10 m3/d in 1999 and the first application with capacity of 110,000 m3/d commissioned in 2009. It is critical to examine the drivers of MBR applications in China, which can provide sound scientific basis for future development of MBR applications. This study summarized the historical development of MBR applications and analyzed the driving forces by survey, literature review and interviews with MBR suppliers. The results showed that: (1) technical advantages of MBR and public policy related to water resources and environment promoted MBR beyond lab and pilot test into wide commercial applications in China; (2) petrochemical industry needs for wastewater treatment and reuse promoted medium-scale MBRs as public policy and regulation on water resources and environment tightens; (3) when the breakthrough of capacity of a single project above 10 thousand m3/d, the Green Olympic Games and Asian Games and tightening effluent regulations in environmentally sensitive areas incentivized MBR applications; and (4) the emergence of 100,000 m3/d MBR was mainly stimulated by water resources stress. Water resources stress and public policy related on resources and the environment are the primary driving forces in the last several decades. The future drivers of MBR applications in China appear to be decreasing operation cost.


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title: Prehospital Emergency Care in Shanghai: Present and Future

text: Abstract Background In Shanghai, prehospital emergency medical services are provided by the public Ambulance Services. The 60th anniversary of the local Ambulance Services is a good opportunity to provide an overview of the current trends in prehospital emergency medical care in Shanghai. Objectives In this report, the features of Shanghai prehospital emergency medical care are described, as well as the Shanghai model of purely prehospital emergency medical care, including the communications and dispatch system, ambulance depots and ambulances, and prehospital rescue teams. Responses to major incidents including public health emergencies and natural disasters are also discussed, with the intention of highlighting future directions in emergency medical services, as well as the influence of international trends in emergency patient care. Discussion Although Shanghai has the most advanced dispatch system in China (equipped with a Global Positioning System, Global Information System, and more) and can be expanded quickly in case of mass casualty incidents, there is, as yet, no uniform Emergency Medical Service (EMS) dispatching for the entire city. Nor are there certifications, degrees, or special continuing education programs available for EMS dispatchers. Although there are more and more ambulance depots spread all over Shanghai, the city struggles with inadequate prehospital emergency caregivers, because every ambulance has to be staffed with a qualified Emergency Physician, and there are also recruitment problems for ambulance physicians. Conclusions Although faced with many challenges, substantial progress is expected in Shanghai prehospital emergency care.


title: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries

text: Abstract The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.


title: Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes

text: BACKGROUND: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. METHODS: From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. RESULTS: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. CONCLUSIONS: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.


title: Transcriptional Regulation of Flotillins by the Extracellularly Regulated Kinases and Retinoid X Receptor Complexes

text: Flotillin-1 and flotillin-2 are important regulators of signal transduction pathways such as growth factor signaling. Flotillin expression is increased under pathological conditions such as neurodegenerative disorders and cancer. Despite their importance for signal transduction, very little is known about the transcriptional regulation of flotillins. Here, we analyzed the expression of flotillins at transcriptional level and identified flotillins as downstream targets of the mitogen activated kinases ERK1/2. The promoter activity of flotillins was increased upon growth factor stimulation in a MAPK dependent manner. Overexpression of serum response factor or early growth response gene 1 resulted in increased flotillin mRNA and protein expression. Furthermore, both promoter activity and expression of endogenous flotillins were increased upon treatment with retinoic acid or by overexpression of the retinoid X receptor and its binding partners RARα and PPARγ. Our data indicate that the expression of flotillins, which can be detected in all cultured cells, is fine-tuned in response to various external stimuli. This regulation may be critical for the outcome of signaling cascades in which flotillins are known to be involved.


title: Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients

text: Abstract Autoimmune reactions associated with MS involve genetic and environmental factors. Because murine coronaviruses induce an MS-like disease, the human coronaviruses (HCoV) are attractive candidates as environmental factors involved in a demyelinating pathology. We previously reported the isolation of HCoV-229E/myelin basic protein (MBP) cross-reactive T-cell lines (TCL) in MS patients. To investigate antigenic cross-reactivity at the molecular level, 155 long-term T-cell clones (TCC) were derived from 32 MS patients by in vitro selection with MBP, proteolipid protein (PLP) or HCoV (strains 229E and OC43). Overall, 114 TCC were virus-specific, 31 were specific for myelin Ag and 10 other were HCoV/myelin cross-reactive. Twenty-eight virus-specific TCC and 7 myelin-specific TCC were obtained from six healthy donors. RACE RT-PCR amplification of the Vβ chains of five of ten the cross-reactive TCC confirmed clonality and sequencing identified the CDR3 region associated with cross-reactivity. Our findings have promising implications in the investigation of the role of molecular mimicry between coronaviruses and myelin in MS as a mechanism related to disease initiation or relapses.


title: Upper airway viruses and bacteria and clinical outcomes in children with cough

text: Background: Cough is symptomatic of a broad range of acute and chronic pediatric respiratory illnesses. No studies in children have tested for an extended panel of upper airway respiratory viruses and bacteria to identify whether they predict cough outcomes, irrespective of clinical diagnosis at the time of acute respiratory illness (ARI). We therefore determined whether upper airway microbes independently predicted hospitalization and persistent cough 28‐days later in children presenting with an ARI, including cough as a symptom. Methods: A cohort study of children aged <15‐years were followed for 28‐days after presenting to a pediatric emergency department with an ARI where cough was also a symptom. Socio‐demographic factors, presenting clinical features and a bilateral anterior nasal swab were collected at enrolment. Polymerase chain reaction assays tested for seven respiratory bacteria and 17 viruses. Predictors of hospitalization and persistent cough at day‐28 were evaluated in logistic regression models. Results: Eight hundred and seventeen children were included in the analysis; median age 27.7‐months. 116 (14.2%, 95%CI 11.8, 16.6) children were hospitalized and 163 (20.0%, 95%CI 17.2, 22.7) had persistent cough at day‐28. Hospitalized children were more likely to have RSV A or B detected on nasal swab than those not admitted (adjusted relative risk (aRR) 1.8, 95%CI 1.0, 3.3). M. catarrhalis was the only microbial difference between children with and without cough persistence (aRR for those with cough at day 28: 2.1, 95%CI 1.3, 3.1). Discussion: An etiologic role for M. catarrhalis in the pathogenesis of persistent cough post‐ARI is worth exploring, especially given the burden of chronic cough in children and its relationship with chronic lung disease. Pediatr Pulmonol. 2017;52:373–381. © 2016 Wiley Periodicals, Inc.


title: Novel multiple swab method enables high efficiency in SARS‐CoV‐2 screenings without loss of sensitivity for screening of a complete population

text: BACKGROUND: In the pandemic, testing for SARS‐CoV‐2 by RT‐PCR is one of the pillars on which countermeasures are based. Factors limiting the output of laboratories interfere with the effectiveness of public health measures. Conserving reagents by pooling samples in low‐probability settings is proposed, but may cause dilution and loss of sensitivity. Blood transfusion services had experience in performance of high throughput NAT analysis and can support the national health system by screening of the inhabitants for SARS‐COV‐2. METHODS: We evaluated a new approach of a multiple swab method by simultaneously incubating multiple respiratory swabs in a single tube. Analytical sensitivity was constant up to a total number of 50 swabs. It was consequently applied in the testing of 50 symptomatic patients (five‐sample pools) as well as 100 asymptomatic residents of a nursing home (ten‐sample pools). RESULTS: The novel method did not cause false negative results with non‐significantly differing Ct values between single swab and multiple swab NAT. In two routine applications, all mini pools containing positive patient samples were correctly identified. CONCLUSIONS: The new method enables countries to increase the total number of testing significantly. The multiple swab method is able to screen system relevant groups of employees frequently. Secondly the example in Germany shows that blood transfusion services can support general health systems with their experience in NAT and their high throughput instruments. Screening of a huge number of inhabitants is currently the only option to prevent a second infection wave and enable exit strategies in many countries. This article is protected by copyright. All rights reserved.


title: Evaluation of scrub typhus diagnosis in China: analysis of nationwide surveillance data from 2006 to 2016

text: BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006–2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (T(diag)) for all cases was 5 days (interquartile range [IQR]: 2–9 days) and decreased from 7 days (IQR: 3–11 days) in 2006 to 5 days (IQR: 2–8 days) in 2016. The risk of death for patients with a T(diag) of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05–5.21) than that of patients with a T(diag) of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0566-0) contains supplementary material, which is available to authorized users.


title: A Call to Introduce Structured Zika Surveillance in India

text: India has the climatic conditions conducive to year-round transmission of Zika virus, and a structured disease surveillance program should be implemented to prevent an outbreak. Such a program should (i) start screening before an outbreak arises; (ii) collect baseline data to assess future disease risk and monitor potential birth defects; and (iii) provide new insights into the ecology of the disease and inform public health policy following the one health concept.


title: Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses

text: The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein, NP, actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention.


title: Kyasanur Forest Disease Classification Framework Using Novel Extremal Optimization Tuned Neural Network in Fog Computing Environment

text: Kyasanur Forest Disease (KFD) is a life-threatening tick-borne viral infectious disease endemic to South Asia and has been taking so many lives every year in the past decade. But recently, this disease has been witnessed in other regions to a large extent and can become an epidemic very soon. In this paper, a new fog computing based e-Healthcare framework has been proposed to monitor the KFD infected patients in an early phase of infection and control the disease outbreak. For ensuring high prediction rate, a novel Extremal Optimization tuned Neural Network (EO-NN) classification algorithm has been developed using hybridization of the extremal optimization with the feed-forward neural network. Additionally, a location based alert system has also been suggested to provide the global positioning system (GPS)-based location information of each KFD infected user and the risk-prone zones as early as possible to prevent the outbreak. Furthermore, a comparative study of proposed EO-NN with state of art classification algorithms has been carried out and it can be concluded that EO-NN outperforms others with an average accuracy of 91.56%, a sensitivity of 91.53% and a specificity of 97.13% respectively in classification and accurate identification of risk-prone areas.


title: IILLS: predicting virus-receptor interactions based on similarity and semi-supervised learning

text: BACKGROUND: Viral infectious diseases are the serious threat for human health. The receptor-binding is the first step for the viral infection of hosts. To more effectively treat human viral infectious diseases, the hidden virus-receptor interactions must be discovered. However, current computational methods for predicting virus-receptor interactions are limited. RESULT: In this study, we propose a new computational method (IILLS) to predict virus-receptor interactions based on Initial Interaction scores method via the neighbors and the Laplacian regularized Least Square algorithm. IILLS integrates the known virus-receptor interactions and amino acid sequences of receptors. The similarity of viruses is calculated by the Gaussian Interaction Profile (GIP) kernel. On the other hand, we also compute the receptor GIP similarity and the receptor sequence similarity. Then the sequence similarity is used as the final similarity of receptors according to the prediction results. The 10-fold cross validation (10CV) and leave one out cross validation (LOOCV) are used to assess the prediction performance of our method. We also compare our method with other three competing methods (BRWH, LapRLS, CMF). CONLUSION: The experiment results show that IILLS achieves the AUC values of 0.8675 and 0.9061 with the 10-fold cross validation and leave-one-out cross validation (LOOCV), respectively, which illustrates that IILLS is superior to the competing methods. In addition, the case studies also further indicate that the IILLS method is effective for the virus-receptor interaction prediction.


title: Human parainfluenza virus types 1–4 in hospitalized children with acute lower respiratory infections in China

text: Human parainfluenza viruses (HPIVs) are an important cause of acute lower respiratory tract infections (ALRTIs). HPIV‐4, a newly identified virus, has been associated with severe ALRTIs recently. A total of 771 nasopharyngeal aspirate samples were collected from hospitalized children between March 2010 and February 2011. HPIVs were detected by Nest‐PCR, and other known respiratory viruses were detected by RT‐PCR and PCR. All amplification products were sequenced. HPIVs were detected in 151 (19.58%) patients, of whom 28 (3.63%) were positive for HPIV‐4, 12(1.55%) for HPIV‐1, 4 (0.51%) for HPIV‐2, and 107 (13.87%) for HPIV‐3. Only three were found to be co‐infected with different types of HPIVs. All HPIV‐positive children were under 5 years of age, with the majority being less than 1 year. Only the detection rate of HPIV‐3 had a significant statistical difference (χ(2) = 29.648, P = 0.000) between ages. HPIV‐3 and HPIV‐4 were detected during the summer. Sixty (39.74%) were co‐infected with other respiratory viruses, and human rhinovirus (HRV) was the most common co‐infecting virus. The most frequent clinical diagnosis was bronchopneumonia, and all patients had cough; some patients who were infected with HPIV‐3 and HPIV‐4 had polypnea and cyanosis. No significant difference was found in clinical manifestations between those who were infected with HPIV‐4 and HPIV‐3. Two genotypes for HPIV‐4 were prevalent, although HPIV‐4a dominated. HPIV‐4 is an important virus for children hospitalized with ALRTIs in China. HRV was the most common co‐infecting virus. Two genotypes for HPIV‐4 are prevalent, HPIV‐4a dominated. J. Med. Virol. 88:2085–2091, 2016. © 2016 Wiley Periodicals, Inc.


Mers-CoV: From camels to humans


title: Relationship between COVID-19 and weather: Case study in a tropical country

text: This study aimed to evaluate the relationship between weather factors (temperature, humidity, solar radiation, wind speed, and rainfall) and COVID-19 infection in the State of Rio de Janeiro, Brazil. Solar radiation showed a strong (-0.609, p < 0.01) negative correlation with the incidence of novel coronavirus (SARS-CoV-2). Temperature (maximum and average) and wind speed showed negative correlation (p < 0.01). Therefore, in this studied tropical state, high solar radiation can be indicated as the main climatic factor that suppress the spread of COVID-19. High temperatures, and wind speed also are potential factors. Therefore, the findings of this study show the ability to improve the organizational system of strategies to combat the pandemic in the State of Rio de Janeiro, Brazil, and other tropical countries around the word.


title: Binding properties of a highly potent and selective iodinated aminopeptidase N inhibitor appropriate for radioautography

text: Aminopeptidase N (APN) is a zinc metallopeptidase involved in the inactivation of biologically active peptides. The knowledge of its precise distribution is crucial to investigate its physiological role. This requires the use of appropriate probes such as the recently developed highly potent and selective radiolabeled APN inhibitor 2(S)-benzyl-3-[hydroxy(1′(R)-aminoethyl)phosphinyl]propanoyl-L-3-[(125)I]iodotyrosine ([(125)I]RB 129). Its binding properties were investigated using rat brain homogenates (K(d)=3.4 nM) or APN expressed in COS-7 cells (K(d)=0.9 nM). The specific binding was 95% at [K(d)], and preliminary autoradiography in intestine is promising. The decreased affinity of [(125)I]RB 129 (=10(−6) M) for the E(350)D APN mutant, supports the critical role of E(350) in the amino-exopeptidase action of APN.


title: Viroporins from RNA viruses induce caspase‐dependent apoptosis

text: The virus‐encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. Here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. Synthesis of 6K protein from Sindbis virus, E from mouse hepatitis virus, M2 from influenza A virus, and 2B and 3A from poliovirus enhanced membrane permeability to different extents. We show that two proteins from hepatitis C virus, p7 and NS4A, also display viroporin activity to a level comparable to 6K protein. In addition to their capacity to disrupt ionic cellular homeostasis and promote bacterial cell lysis, the expressed viroporins were able to induce cell death. Degradation of internucleosomal DNA and generation of apoptotic bodies were observed upon viroporin expression. Consistently, cleavage of translation initiation factor 4GI and poly‐(ADP‐ribose) polymerase indicated activation of effector caspase‐3. We found that poliovirus 2B localizes partially in mitochondria and induces an anomalous perinuclear distribution of these organelles. Mitochondria morphology was also altered after expression of other viroporins. Finally, detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin‐induced apoptosis. These findings suggest that viroporins induce caspase‐dependent programmed cell death.


title: Chapter 21 Genosensor on gold films with enzymatic electrochemical detection of a SARS virus sequence

text: Abstract Biosensors are one of the best examples of miniaturization and simplification trends in analytical chemistry. Among them, DNA sensors, with oligonucleotides as recognition elements, are being widely utilized for many applications, mainly diagnosis of infectious diseases. In this experiment, a hybridization-based genosensor was designed on a 100-nm sputtered gold film. This material worked as an immobilization and transduction surface for the electrochemical diagnosis of a specific DNA sequence of SARS (severe acute respiratory syndrome) virus. The simplicity of the electrochemical instrumentation is combined with a selective methodology to detect the hybridization event enzymatically. This chapter explains all the necessary steps for the construction of the genosensor allowing a low detection limit for the chosen DNA sequence. Protocols for studying the influence of parameters affecting the methodology are given. This chapter also includes questions for students and indications for writing a lab report.


title: Epidemiology studies in critical care

text: Epidemiology studies are an essential part of clinical research, often forming the foundation for studies ranked more highly in the hierarchy of evidence-based medicine. Studies of sepsis to date have been conducted on local, regional, national and international scales, with the majority conducted in the past 5 years. Longitudinal epidemiology studies convey an important additional aspect of the healthcare burden from disease, and may additionally serve to compare the effectiveness and efficiency of healthcare systems, to examine specific patient care strategies and to perform quality control analyses.


title: Life after acute fibrinous and organizing pneumonia: a case report of a patient 30 months after diagnosis and review of the literature

text: Abstract Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern recently described in the literature with fewer than 120 cases published. AFOP is often difficult to diagnose and may be mistaken for other pulmonary disorders such as interstitial pneumonias or pneumonitides. Patients often present with vague symptoms of cough, dyspnea, hemoptysis, fatigue, and occasionally respiratory failure. Radiological findings show diffuse patchy opacities and ground glass appearance of the lungs. On histologic examination, intra-alveolar fibrin balls are observed. We discuss a case of a man who presented with hemoptysis and dyspnea and whose open lung biopsy revealed AFOP. We will describe the presentation, diagnosis, and post-discharge course, and review the current literature. There are only 4 cases which have reported the patients’ course of disease after 1 year, the longest being 2 years. To our knowledge, this is the only case of AFOP in the literature that describes the course of a patient more than 2 years after the diagnosis of AFOP, and is the most comprehensive review of the current literature.


title: Clinical characteristics of 182 pediatric COVID‐19 patients with different severities and allergic status

text: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID‐19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10 and TNF‐α.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non‐allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non‐allergic COVID‐19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.


Editorial Commentary: Critical Contribution of Laboratories to Outbreak Response Support for Middle East Respiratory Syndrome Coronavirus


title: Occupational exposure to infection risk and use of personal protective equipment by emergency medical personnel in the Republic of Korea

text: BACKGROUND: Few studies of occupational exposure (OE) to infectious risk among emergency medical personnel (EMP) or their use of personal protective equipment (PPE) have been conducted in the Republic of Korea. OBJECTIVE: To determine the status of OE to infectious risks and use of PPE. METHODS: A convenience sample of 907 questionnaires (response rate, 88.5%) was collected from September 1, 2014, to January 31, 2015, in 5 metropolitan Korean cities. RESULTS: Respiratory diseases were significantly prevalent (44.5%) and influenza (29.5%) was the most frequently reported illness. An exposure report was only made in 19.5% of cases. The primary reason for OE report noncompletion was the complexity of the reporting process (23.9%). A total of 365 participants reported OE to body fluids and blood (40.2%) with needlestick injury being the most frequent OE type (17.6%). More than 5 years of job experience (47.8%) (P < .001) and region (city) (P = .003) significantly increased OE to body fluids and blood. Puncture-resistant containers (71.9%) and disposable gloves (68.9%) were used. Job training and education on infection risks and use of PPE were not uniformly conducted (77.5%). Anxiety about OE to risk of infection from patients was common among EMP (63.2%). CONCLUSIONS: EMP experienced significant OE to infectious risk and use PPE inadequately. Surveillance and education programs regarding OE should be developed.


docid: zawfotcx

title: Creating a Palliative Care Inpatient Response Plan for COVID-19—The UW Medicine Experience

text: Abstract Context The coronavirus disease 2019 (COVID-19) pandemic is stressing health care systems throughout the world. Significant numbers of patients are being admitted to the hospital with severe illness, often in the setting of advanced age and underlying comorbidities. Therefore, palliative care is an important part of the response to this pandemic. The Seattle area and UW Medicine have been on the forefront of the pandemic in the U.S. Methods UW Medicine developed a strategy to implement a palliative care response for a multihospital health care system that incorporates conventional capacity, contingency capacity, and crisis capacity. The strategy was developed by our palliative care programs with input from the health care system leadership. Results In this publication, we share our multifaceted strategy to implement high-quality palliative care in the context of the COVID-19 pandemic that incorporates conventional, contingency, and crisis capacity and focuses on the areas of the hospital caring for the most patients: the emergency department, intensive care units, and acute care services. The strategy focuses on key content areas, including identifying and addressing goals of care, addressing moderate and severe symptoms, and supporting family members. Conclusion Strategy planning for delivery of high-quality palliative care in the context of the COVID-19 pandemic represents an important area of need for our health care systems. We share our experiences of developing such a strategy to help other institutions conduct and adapt such strategies more quickly.


title: Unraveling the Structure of Viral Replication Complexes at Super-Resolution

text: During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.


title: Amyotrophic lateral sclerosis care and research in the United States during the COVID‐19 pandemic: Challenges and opportunities

text: Coronavirus disease 2019 has created unprecedented challenges for amyotrophic lateral sclerosis (ALS) clinical care and research in the United States. Traditional evaluations for making an ALS diagnosis, measuring progression, and planning interventions rely on in‐person visits that may now be unsafe or impossible. Evidence‐ and experience‐based treatment options, such as multidisciplinary team care, feeding tubes, wheelchairs, home health, and hospice, have become more difficult to obtain and in some places are unavailable. In addition, the pandemic has impacted ALS clinical trials by impairing the ability to obtain measurements for trial eligibility, to monitor safety and efficacy outcomes, and to dispense study drug, as these also often rely on in‐person visits. We review opportunities for overcoming some of these challenges through telemedicine and novel measurements. These can reoptimize ALS care and research in the current setting and during future events that may limit travel and face‐to‐face interactions.


title: Multiple recombination events between field and vaccine strains resulted in the emergence of a novel infectious bronchitis virus with decreased pathogenicity and altered replication capacity

text: Abstract In this study, we isolated and identified 2 infectious bronchitis virus (IBV) strains from layer chickens soon after vaccination with the Massachusetts–Connecticut bivalent vaccine (Conn) and H120 and 4/91 booster vaccines in China in 2011. The results of cross-virus-neutralization tests and phylogenetic analysis of the S1 subunit of spike gene of these vaccine strains and other reference strains showed that strain LJL/110302 was of GI-19 lineage, whereas LLN/111169 was of the GI-1 lineage of the Conn serotype. Further comparative genomic analysis revealed that LLN/111169, an IBV strain with novel traits, originated from multiple recombination events (at least 3 recombination sites) between GI-19 and the Conn and 4/91 vaccine strains. LLN/111169 was pathogenic to specific pathogen-free (SPF) chickens. This is of prime importance because while IBV prevention measures worldwide are mainly dependent on modified live vaccine strains, our results showed that recombination between field and vaccine strains has produced a novel pathogenic IBV strain. In addition, LLN/111169 showed relatively broad tissue tropism (trachea, lungs, kidneys, and cecal tonsils) in infected SPF chickens. These results emphasize the importance of IBV surveillance in chicken flocks.


title: Coronavirus disease 2019 (COVID-19) pneumonia incidentally detected on coronary CT angiogram: a do-not-miss diagnosis

text: Coronary CT angiograms are commonly performed for the evaluation of coronary artery disease and coronary arterial anatomy. However, extracardiac findings are frequently detected on these examinations and often can explain patients’ underlying symptoms, having a significant impact on patient management. Here in, we discuss three cases of incidentally detected novel COVID-19-infected pneumonia (NCIP). This case series highlights the image findings in NCIP and emphasizes the importance of evaluating all organs in the field of view on coronary CT angiograms. In addition, with the ongoing outbreak of COVID-19 and exponentially increasing incidence throughout the world, this report stresses the need for including NCIP in the differential diagnosis of patients with typical image findings in at-risk populations, as early diagnosis is crucial for appropriate patient management and post-exposure recommendations.


title: Multiplex real–time RT–PCR for detecting chikungunya virus and dengue virus

text: Abstract Objective To develop diagnostic test for detection chikungunya virus (CHIKV and Dengue virus (DENV) infection. Methods We have performed a rapid, accurate laboratory confirmative method to simultaneously detect, quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR. Results The assay's sensitivity was 97.65%, specificity was 92.59% and accuracy was 95.82% when compared to conventional RT-PCR. Additionally, there was no cross-reaction between CHIKV, DENV, Japanese encephalitis virus, hepatitis C, hepatitis A or hepatitis E virus. Conclusions This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.


title: Preliminary estimation of the novel coronavirus disease (COVID-19) cases in Iran: A modelling analysis based on overseas cases and air travel data

text: Abstract As of March 1, 2020, Iran had reported 987 novel coronavirus disease (COVID-19) cases, including 54 associated deaths. At least six neighboring countries (Bahrain, Iraq, Kuwait, Oman, Afghanistan, and Pakistan) had reported imported COVID-19 cases from Iran. In this study, air travel data and the numbers of cases from Iran imported into other Middle Eastern countries were used to estimate the number of COVID-19 cases in Iran. It was estimated that the total number of cases in Iran was 16 533 (95% confidence interval: 5925–35 538) by February 25, 2020, before the UAE and other Gulf Cooperation Council countries suspended inbound and outbound flights from Iran.


title: Viruses in Vietnamese Patients Presenting with Community-Acquired Sepsis of Unknown Cause

text: Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015. Specific monoplex PCRs were used subsequently to confirm the presence of viral sequences detected by mNGS. We found sequences related to 47 viral species belonging to 21 families in 358 of 386 (93%) patients, including viruses known to cause human infections. After PCR confirmation, human viruses were found in 52 of 386 patients (13.4%); picornavirus (enteroviruses [n = 14], rhinovirus [n = 5], and parechovirus [n = 2]), hepatitis B virus (n = 10), cytomegalovirus (n = 9), Epstein-Barr virus (n = 5), and rotavirus A (n = 3) were the most common viruses detected. Recently discovered viruses were also found (gemycircularvirus [n = 5] and WU polyomavirus, Saffold virus, salivirus, cyclovirus-VN, and human pegivirus 2 [HPgV2] [n, 1 each]), adding to the growing literature about the geographic distribution of these novel viruses. Notably, sequences related to numerous viruses not previously reported in human tissues were also detected. To summarize, we identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. The study, however, cannot directly impute sepsis causation to the viruses identified. The results highlight the fact that it remains a challenge to establish the causative agents in CA sepsis patients, especially in tropical settings such as Vietnam.


title: A DNA biochip for on-the-spot multiplexed pathogen identification

text: Miniaturized integrated DNA analysis systems have largely been based on a multi-chamber design with microfluidic control to process the sample sequentially from one module to another. This microchip design in connection with optics involved hinders the deployment of this technology for point-of-care applications. In this work, we demonstrate the implementation of sample preparation, DNA amplification, and electrochemical detection in a single silicon and glass-based microchamber and its application for the multiplexed detection of Escherichia coli and Bacillus subtilis cells. The microdevice has a thin-film heater and temperature sensor patterned on the silicon substrate. An array of indium tin oxide (ITO) electrodes was constructed within the microchamber as the transduction element. Oligonucleotide probes specific to the target amplicons are individually positioned at each ITO surface by electrochemical copolymerization of pyrrole and pyrrole−probe conjugate. These immobilized probes were stable to the thermal cycling process and were highly selective. The DNA-based identification of the two model pathogens involved a number of steps including a thermal lysis step, magnetic particle-based isolation of the target genomes, asymmetric PCR, and electrochemical sequence-specific detection using silver-enhanced gold nanoparticles. The microchamber platform described here offers a cost-effective and sample-to-answer technology for on-site monitoring of multiple pathogens.


Olfactory dysfunction in recovered COVID‐19 patients