title: Canine babesiosis among working dogs of organised kennels in India: A comprehensive haematological, biochemical, clinicopathological and molecular epidemiological multiregional study

text: Abstract Canine babesiosis is a serious disease among tick-borne haemoprotozoan diseases, globally. The present study was envisaged for carrying out thorough investigation of the disease among working dogs of organised kennels situated in different agro-climatic zones of India as comprehensive understanding of the disease from this country was pertinently lacking. During the study period of three years (2012–2014), 330 dogs suspected for babesiosis were examined for clinicopathology by their physical examination, haematological and biochemical parameters estimation, while the detection of apicomplexan parasites was confirmed by using various diagnostic techniques i.e. by conventional microscopy, by two different Babesia specific 18S rRNA based PCR protocols (conventional/simple PCR and nested PCR assays) followed by sequencing of obtained PCR amplicons for Babsesia spp. identification. Out of 330 clinical cases screened 5.15% (17/330), 9.09% (30/330) and 15.45% (51/330) were found to be positive in microscopic examination, simple- and nested- PCR assay, respectively. Comparative statistical analyses of these diagnostic assay results revealed that significant difference exists among the three diagnostic methodologies and thus it is recommended that the nested PCR technique be relied upon as a screening molecular assay and also for epidemiological studies of the disease in this country. Phylogenetic analysis based on 18S rRNA depicted the monophyletic nature and clonal expansion among all the B. gibsoni, under study. Sequencing results of PCR amplicons revealed that B. gibsoni has predominantly established itself over B. vogeli as former was incriminated in 47 cases while latter was confirmed in only four animals. Based on the clinical severity, these 51 affected animals were classified into three main groups’ of 17 animals each viz., apparently healthy-, simple or uncomplicated babesiosis- and atypical or complicated babesiosis- group. Haematological and biochemical profiling of these dogs confirmed the characteristics findings of infection by both the Babesia spp. It was observed that the infection by small form of Babesia (B. gibsoni) is posing a significant therapeutic challenge and chemosterilization by commonly prescribed anti-protozoal drugs was not achieved as clinical relapses were often observed. The clinical signs, sequence based confirmation and severity of the infection suggested that there is a positive selection of B. gibsoni (smaller form) over B. vogeli (larger form) in this country and raises serious concerns as prognosis in former is considered to be poor compared to latter. Thus, these findings have opened new paradigms for planning of pragmatic control strategies against this emerging canine health problem.


docid: oyljpsfq

title: Characterization of the inflammatory response in the central nervous system of rats with different susceptability to coronavirus MHV4-induced encephalitis


title: Clinical risk factors associated with the development of wheezing in children less than 2 years of age who required hospitalization for viral lower respiratory tract infections

text: PURPOSE: Wheezing following viral lower respiratory tract infections (LRTIs) in children <2 years of age is an important risk factor for the development of asthma later in life; however, not all children with viral LRTIs develop wheezing. This study investigated risk factors for the development of wheezing during viral LRTIs requiring hospitalization. METHODS: The study included 142 children <2 years of age hospitalized for LRTIs with at least one virus identified as the cause and classified them into children diagnosed with LRTIs with wheezing (n=70) and those diagnosed with LRTIs without wheezing (n=72). RESULTS: There were no significant differences in the viruses detected between the two groups. Multivariate logistic regression analysis showed that, after adjusting for potentially confounding variables including sex and age, the development of wheezing was strongly associated with parental history of allergic diseases (adjusted odds ratio [aOR], 20.19; 95% confidence interval [CI], 3.22-126.48), past history of allergic diseases (aOR, 13.95; 95% CI, 1.34-145.06), past history of hospitalization for respiratory illnesses (aOR, 21.36; 95% CI, 3.77-120.88), exposure to secondhand smoke at home (aOR, 14.45; 95% CI, 4.74-44.07), and total eosinophil count (aOR, 1.01; 95% CI, 1.01-1.02). CONCLUSION: Past and parental history of allergic diseases, past history of hospitalization for respiratory illnesses, exposure to secondhand smoke at home, and total eosinophil count were closely associated with the development of wheezing in children <2 years of age who required hospitalization for viral LRTIs. Clinicians should take these factors into consideration when treating, counseling, and monitoring young children admitted for viral LRTIs.


docid: upcsvjuo

title: Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study

text: [Image: see text] The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson–Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev.2019, 119, 947831244000; Wang, Curr. Comput.-Aided Drug Des.2006, 2, 287; Wang; HouJ. Chem. Inf. Model., 2012, 52, 119922497310). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, −13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (−3.8 kcal/mol) is not nearly as low as that of the neutral form (−7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of −12.9 kcal/mol. Detailed receptor–ligand interactions were analyzed and hot spots for the receptor–ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.


Lessons learned from new emerging infectious disease, Middle East Respiratory Syndrome coronavirus outbreak in Korea


title: Molecular Characterization of Transmissible Gastroenteritis Coronavirus Defective Interfering Genomes: Packaging and Heterogeneity

text: Abstract Three transmissible gastroenteritis virus (TGEV) defective RNAs were selected by serial undiluted passage of the PUR46 strain in ST cells. These RNAs of 22, 10.6, and 9.7 kb (DI-A, DI-B, and DI-C, respectively) were detected at passage 30, remained stable upon further passage in cell culture, and significantly interfered with helper mRNA synthesis. RNA analysis from purified virions showed that the three defective RNAs were efficiently packaged. Virions of different densities containing either full-length or defective RNAs were sorted in sucrose gradients, indicating that defective and full-length genomes were independently encapsidated. DI-B and DI-C RNAs were amplified by the reverse transcription-polymerase chain reaction, cloned, and sequenced. DI-B and DI-C genomes are formed by three and four discontinuous regions of the wild-type genome, respectively. DI-C contains 2144 nucleotides (nt) from the 5′-end of the genome, two fragments of 4540 and 2531 nt mostly from gene 1b, and 493 nt from the 3′ end of the genome. DI-B and DI-C RNAs include sequences with the pseudoknot motif and encoding the polymerase, metal ion binding, and helicase motifs. DI-B RNA has a structure closely related to DI-C RNA with two main differences: it maintains the entire ORF 1b and shows heterogeneity in the size of the 3′ end deletion. This heterogeneity maps at the beginning of the S gene, where other natural TGEV recombination events have been observed, suggesting that either a process of template switching occurs with high frequency at this point or that the derived genomes have a selective advantage.


title: Trauma Transformed: A positive review of change during the COVID-19 pandemic

text: Charles Moore in The Telegraph recently described the NHS as ‘lumbering’.(1) Far from this description, it has been our experience that the NHS has rapidly transformed across specialties in order to respond to the unprecedented global crisis of COVID-19. We describe here the multiple ways in which the plastic surgery trauma service at Salisbury District Hospital swiftly adapted over a two-week period in March 2020. Our aim is to deliver a tailored trauma service whilst adhering to the same high standards of patient care established prior to the COVID-19 pandemic. It is our view that many of these changes will be positive enduring practices for the future.


title: Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum

text: Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites. We demonstrate that PfRhopH3 binds to the RBCs and their treatment with Cyclosporin A prevents merozoite invasion. We also show a multi-protein complex involving Cyclophilin B and Basigin, as well as PfRhopH3 and PfRh5 that aids the invasion. Furthermore, we report identification of a de novo peptide CDP3 that binds Cyclophilin B and blocks invasion by up to 80%. Collectively, our data provide evidence of compounded interactions between host receptors and merozoite surface proteins and paves the way for developing peptide and small-molecules that inhibit the protein−protein interactions, individually or in toto, leading to abrogation of the invasion process.


title: Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1–3, most targeting the viral ‘spike’ glycoprotein (S) S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4–6 Eliciting neutralizing antibodies that block S–ACE2 interaction7–9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11 However, although prototypic S-based vaccines show promise in animal models12–14, the immunogenic properties of S in humans are poorly resolved In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19) We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes


COVID-19 pandemic and its impact on cardiology and its subspecialty training()


title: Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 outbreak in China: a web-based cross-sectional survey

text: Abstract China has been severely affected by Coronavirus Disease 2019(COVID-19) since December, 2019. We aimed to assess the mental health burden of Chinese public during the outbreak, and to explore the potential influence factors. Using a web-based cross-sectional survey, we collected data from 7,236 self-selected volunteers assessed with demographic information, COVID-19 related knowledge, generalized anxiety disorder (GAD), depressive symptoms, and sleep quality. The overall prevalence of GAD, depressive symptoms, and sleep quality of the public were 35.1%, 20.1%, and 18.2%, respectively. Young people reported a significantly higher prevalence of GAD and depressive symptoms than older people. Compared with other occupational group, healthcare workers were more likely to have poor sleep quality. Multivariate logistic regression showed that age (< 35 years) and time spent focusing on the COVID-19 (≥ 3 hours per day) were associated with GAD, and healthcare workers were at high risk for poor sleep quality. Our study identified a major mental health burden of the public during the COVID-19 outbreak. Young people, people spending too much time thinking about the outbreak, and healthcare workers were at high risk of mental illness. Continuous surveillance of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide.


title: A Mixture of Dioxins, Furans, and Non-ortho PCBs Based upon Consensus Toxic Equivalency Factors Produces Dioxin-Like Reproductive Effects

text: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) and related polyhalogenated aromatic hydrocarbons (PHAHs) alter the reproductive development of laboratory animals. Therefore, we exposed animals to a mixture of dioxins, furans, and polychlorinated biphenyls (PCBs) that included TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), octachlorodibenzofuran (OCDF), 3,3′,4,4′-tetrachlorobiphenyl (PCB77), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), and 3,3′,4,4′,5,5′-hexachlorobiphenyl (PCB169). The mixture composition approximated the relative abundance of these compounds in foodstuff (L. S. Birnbaum and M. J. DeVito, 1995, Toxicology Vol. 105, pp. 391–401). Following the work of Gray et al. with TCDD (1997, Toxicology and Applied Pharmacology Vol. 146, pp. 11–20), we exposed time-pregnant dams on gestation day (GD) 15 at doses up to 1.0 μg TCDD toxic equivalency (TEQ)/kg and the development of offspring was monitored. This mixture significantly increased the time to puberty in both male and female offspring. At postnatal day (PND) 32 seminal vesicle weights were decreased; however, only ventral prostate weight was affected at PND 49 and no effects were seen at PND 63. In female offspring, the mixture caused dose-dependent increases in the incidence of vaginal thread. Ethoxyresorufin-O-deethylase (EROD) activity was higher than with TCDD the comparable TEQ exposure. Based on the slightly lowered responsiveness to the mixture, we used 2.0 μg TEQ/kg to examine reproductive effects. This dose elicited the responses observed with 1.0 μg TCDD/kg. Results indicate that the mixture causes a similar spectrum of effects seen with TCDD and the slightly lowered degree of response based on administered dose appears to be due to decreased transfer of mixture components to the offspring. Thus, the use of the WHO consensus TEFs (M. Van den Berg et al., 1998, Environ. Health Perspec. 106, 775–792) reasonably predicts the developmental toxicity of this mixture of dioxin-like PHAHs.


title: The Diagnosis of SARS‐CoV2 Pneumonia: A Review of Laboratory and Radiological Testing Results

text: The rapid emergence of COVID‐19 (coronavirus disease 2019) has necessitated the implementation of diverse pandemic control strategies throughout the world. In order to effectively control the spread of this disease, it is essential that it be diagnosed at an early stage so that patients can be reliably quarantined such that disease spread will be slowed. At present, the diagnosis of this infectious form of coronavirus pneumonia is largely dependent upon a combination of laboratory testing and imaging analyses of variable diagnostic efficacy. In the present report, we reviewed prior literature pertaining to the diagnosis of different forms of pneumonia caused by coronaviruses (SARS, MERS, and SARS‐CoV‐2) and assessed two different potential diagnostic approaches. We ultimately found that computed tomography (CT) was associated with a higher rate of diagnostic accuracy than was a real‐time quantitative polymerase chain reaction (qPCR)‐based approach (P = 0.0041), and chest radiography (P = 0.0100). Even so, it is important that clinicians utilize a combination of laboratory and radiological testing where possible in order to ensure that this virus is reliably and quickly detected such that it may be treated and patients may be isolated in a timely fashion, thereby effectively curbing the further progression of this pandemic. This article is protected by copyright. All rights reserved.


Management of adult patients with severe atopic dermatitis treated with dupilumab during COVID‐19 pandemic: a single‐center real‐life experience


title: Association of ICAM3 Genetic Variant with Severe Acute Respiratory Syndrome

text: Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3 were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS-CoV infection was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P=.0067; odds ratio [OR], 4.31 [95% confidence interval [CI], 1.37–13.56]) and lower total white blood cell counts (P=.022; OR, 0.30 [95% CI, 0.10–0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS.


title: Diagnostic value of combined nucleic acid and antibody detection in suspected COVID-19 cases

text: Abstract Objectives Nucleic acid testing is the gold-standard method for the diagnosis of coronavirus disease 2019 (COVID-19); however, large numbers of false-negative results have been reported. In this study, nucleic acid detection and antibody detection (IgG and IgM) were combined in order to improve the testing accuracy of suspected COVID-19 patients. Study design xxxx Methods A total of 71 suspected COVID-19 patients were selected to participate in this study, which included a retrospective analysis of clinical features, imaging examination, laboratory biochemical examination, and nucleic acid detection and specific antibody (IgM and IgG) detection. Results The majority of participants with suspected COVID-19 presented with fever (67.61%) and cough (54.93%), and imaging results showed multiple small patches and ground-glass opacity in both lungs, with less common infiltration and consolidation opacity (23.94%). Routine blood tests were mostly normal (69.01%), while only a few patients had lymphopenia (4.23%) or leukopenia (12.68%). There was no statistical difference in the double-positive rate between nucleic acid detection (46.48%) and specific antibody (IgG and IgM) detection (42.25%) (P = 0.612); both of which were also poorly consistent with each other (Kappa = 0.231). The positive rate of combined nucleic acid detection and antibody detection (63.38%) was significantly increased, compared with that of nucleic acid detection (46.48%) and that of specific antibody (IgG and IgM) detection (42.25%), and the differences were statistically significant (P = 0.043 and P = 0.012, respectively). Conclusions Nucleic acid detection and specific antibody (IgG and IgM) detection had similar positive rates, and their combination could improve the positive rate of COVID-19 detection, which is of great significance for diagnosis and epidemic control.


title: Cytopathic effects: virus-modulated manifestations of innate immunity?

text: The capacity to injure infected cells is a widespread property of viruses. Usually, this cytopathic effect (CPE) is ascribed to viral hijacking of cellular resources to fulfill viral needs. However, evidence is accumulating that CPE is not necessarily directly coupled to viral reproduction but may largely be due to host defensive and viral antidefensive activities. A major part in this virus–cell interaction appears to be played by a putative host-encoded program with multiple competing branches, leading to necrotic, apoptotic, and, possibly, other types of cell suicide. Manifestations of this program are controlled and modulated by host, viral, and environmental factors.


title: Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells

text: Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.


title: Receptors and ligands involved in viral induction of type I interferon production by plasmacytoid dendritic cells

text: Abstract Virus infection is sensed by the innate immune system which then rapidly initiates biosynthesis of type I interferon (IFN). The IFN signaling systems produce a broadly effective innate antiviral response by creating an antiviral state in both an autocrine and paracrine manner in cells and by activating innate and adaptive immunity. Plasmacytoid dendritic cells (pDCs) have the unique ability to produce very high levels of type I IFN following viral infection in vivo. Most recent research has focused on oligonucleotide-mediated induction of type I IFN production, implicating viral genome and replication intermediates as the stimulus for this response. However there are additional viral ligands which can potentially induce type I IFN production in pDCs, such as envelope glycoproteins, viral glycolipids, tegument, capsid or nuclear proteins. This area of viral immunology, which has been neglected in the literature, will be discussed here.


title: Agents associated with neonatal diarrhoea in Ethiopian dairy calves

text: Faeces samples collected from diarrhoeic dairy calves in the first 8 weeks of life were examined for the presence of 5 enteropathogens. The majority of the 108 diarrhoea cases occurred in the first 5 weeks of life and a commercial ELISA kit detected bovine enteric coronavirus (BEC) in 38.9%, serogroup A rotavirus (RV) in 16.7% and K99 (F5) fimbrial adhesin-positiveEscherichia coli (K99 ETEC) in 11.1 per cent. Concurrent infections of these enteropathogens were detected in 14.8% of samples (30.8% of samples positive for these agents). No evidence of cryptosporidial infection was found using a differential staining method on faecal smears nor was salmonella excretion detected. On 2 of the 8 farms only BEC was present; the other 6 farms were positive for all 3 agents. It is concluded that BEC is the major infectious cause of neonatal calf diarrhoea in the Ethiopian dairy herds studied with RV and K99 ETEC also contributing to morbidity, either alone or as mixed infections.


title: An agent-based model driven by tropical rainfall to understand the spatio-temporal heterogeneity of a chikungunya outbreak

text: Abstract Vector-borne diseases, such as dengue, malaria and chikungunya, are increasing across their traditional ranges and continuing to infiltrate new, previously unaffected, regions. The spatio-temporal evolution of these diseases is determined by the interaction of the host and vector, which is strongly dependent on social structures and mobility patterns. We develop an agent-based model (ABM), in which each individual is explicitly represented and vector populations are linked to precipitation estimates in a tropical setting. The model is implemented on both scale-free and regular networks. The spatio-temporal transmission of chikungunya is analysed and the presence of asymptomatic silent spreaders within the population is investigated in the context of implementing travel restrictions during an outbreak. Preventing the movement of symptomatic individuals is found to be an insufficient mechanism to halt the spread of the disease, which can be readily carried to neighbouring nodes via sub-clinical individuals. Furthermore, the impact of topology structure vs. precipitation levels is assessed and precipitation is found to be the dominant factor driving spatio-temporal transmission.


title: Household transmission of influenza virus

text: Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection.


Managing Asthma during COVID-19: An Example for Other Chronic Conditions in Children and Adolescents


title: Afectación del aparato digestivo en la COVID-19. Una revisión sobre el tema

text: RESUMEN La pandemia por el SARS-CoV-2 está conllevando una elevada mortalidad y suponiendo una crisis sanitaria a nivel mundial. La afectación fundamental es respiratoria; sin embargo, el virus también puede afectar a otros órganos, como el tracto gastrointestinal y el hígado. Los síntomas más habituales son anorexia y diarrea. Aproximadamente, en la mitad de los casos se podría detectar RNA viral en heces, lo que constituye otra línea de transmisión y diagnóstico. La COVID19 tiene peor pronóstico en pacientes con comorbilidades, aunque no existe evidencia suficiente en caso de patologías digestivas previas. Las endoscopias digestivas pueden originar aerosoles, que las convierten en técnicas con elevado riesgo de infección. Expertos y organizaciones científicas a nivel mundial han elaborado guías de funcionamiento para adoptar medidas de prevención. Se revisan las evidencias disponibles sobre la afectación gastrointestinal y hepática, la repercusión en pacientes con enfermedades digestivas previas y guías de funcionamiento para Unidades de Endoscopia durante la pandemia. ABSTRACT The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. COVID19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.


title: The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy

text: BACKGROUND: The role of viruses in children with respiratory tract infections and humoral immunodeficiencies has hardly been studied. We have evaluated these infections in children with humoral immunodeficiencies who required immunoglobulin replacement therapy, considering their relationship with symptoms, lung function, bacterial co‐infection, and outcomes. METHODS: We conducted a prospective case‐control study during a 1‐year period, including children with humoral immunodeficiencies receiving immunoglobulin replacement therapy. For each patient, at least one healthy family member was included. Respiratory samples for viral detection were taken every 1‐3 months, and in case of respiratory tract infections. Symptoms questionnaires were filled biweekly. Spirometry and sputum culture were performed in every episode. RESULTS: Sixty‐six episodes were analyzed in 14 patients (median age 12 years; IQR 7‐17), identifying 18 respiratory viruses (27.3%), being rhinovirus the most frequently isolated one (12/18; 66%). Positive viral episodes were associated with clinical symptoms (89% vs 43%), more frequent antibiotic treatment (44% vs 15%) or hospital admission (22% vs 0%) than negative ones. Patients with positive viral detection showed impaired lung function, with lower FEV1 and FVC values. CONCLUSIONS: In our experience, viral respiratory tract infections can cause significant respiratory symptoms and impaired lung function, in children with HID, despite immunoglobulin replacement therapy. These patients could benefit from the monitoring of viral infections, as these may be a gateway for ongoing lung damage.


title: Impact of highly active antiretroviral therapy on organ‐specific manifestations of HIV‐1 infection

text: In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ‐specific manifestations of HIV‐1 infection. There has been a clear step‐wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ‐specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ‐specific manifestations, including HIV‐associated nephropathy, wasting syndrome and cardiomiopathy, are a direct consequence of damage by HIV‐1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV‐1 organ‐specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ‐specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV‐1‐related neoplasia.


title: Pyogranulomatous skin disease and cellulitis in a cat caused by Rhodococcus equi

text: This report describes a case of Rhodococcus equi infection causing pyogranulomatous skin disease and cellulitis in a two‐year‐old female domestic shorthaired cat. The case differed from previously reported cases in cats in its clinical presentation and in the locations of the lesions, which were similar to those seen in horses. The presence of an intracellular organism was confirmed by cytology and on histopathology. The aetiological diagnosis was confirmed by routine biochemical tests specific for R equi on a pure isolate obtained from a biopsy specimen. The report also reviews the literature of the documented feline cases and discusses the common pitfalls in the diagnosis of such infections.


title: Antiviral therapy for respiratory viral infections in immunocompromised patients

text: Introduction: Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.


title: A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis

text: In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection of individual hosts within a population. Model output is the dose–response relation and the dose-dependent distribution of time until response, where response is the onset of symptoms. The model is thereafter parametrized with respect to the highly virulent Schu S4 strain of Francisella tularensis, in the first such study to consider a biologically plausible mathematical model for early human infection with this bacterium. Results indicate a median infectious dose of about 23 organisms, which is higher than previously thought, and an average incubation period of between 3 and 7 days depending on dose. The distribution of incubation periods is right-skewed up to about 100 organisms and symmetric for larger doses. Moreover, there are some interesting parallels to the hypotheses of some of the classical dose–response models, such as independent action (single-hit model) and individual effective dose (probit model). The findings of this study support experimental evidence and postulations from other investigations that response is, in fact, influenced by both in-host and between-host variability.


title: Chapter 15 Molecular Testing in Emerging Infectious Diseases

text: Abstract It was widely believed in the late 1960s that infectious diseases had been conquered by vaccines and antibiotics and humans were no longer under threat by microbial pathogens. Yet, since that time more than 60 pathogens have been discovered that can cause serious emerging infectious diseases. Molecular methods have played critical roles in the discovery, monitoring, and clinical diagnostics of emerging pathogens. In this chapter, we present well-recognized emerging pathogens. We provide examples of the utility of molecular assays in research and clinical care of emerging infectious diseases. We also discuss some theoretical and practical limitations of molecular tests and the future prospects of expanding molecular diagnostics for emerging pathogens based on new advances of knowledge and technologies.


title: High depression and anxiety in people with Alzheimer's disease living in retirement homes during the Covid-19 crisis

text: To cope with Covid-19 and limits its spread among residents, retirement homes have prohibited physical contact between residents and families and friend and, in some cases, even between residents or between residents and caregivers. We investigated the effects of measures against Covid-19 on the mental health of participants with Alzheimer's disease (AD) who live in retirement homes in France. We instructed on-site caregivers to assess depression and anxiety in participants with mild AD who live in retirement homes. Fifty-eight participants consented to participate in the study. The participants rated their depression and anxiety during and before the Covid-19 crisis. Participants reported higher depression (p = .005) and anxiety (p = .004) during than before the Covid-19 crisis. These increases can be attributed to the isolation of the residents and/or to the drastic changes in their daily life and care they receive. While, in their effort to prevent infections, retirement homes are forced to physically separate residents from the outside world and to drastically reduce residents’ activities, these decisions are likely to come at a cost to residents with AD and their mental health.


title: microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro

text: Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and upregulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed proteins were gained. The target of miR-4331 was identified. The effects of miR-4331 and its target RB1 on mitochondrial Ca(2+) level, mitochondrial membrane potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK signaling pathway were investigated. The results showed that miR-4331 elevated mitochondrial Ca(2+) level, reduced MMP, targets Retinoblastoma 1 (RB1), upregulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV infection. RB1 was identified as the direct targets of miR-4331 and downregulated IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced mitochondrial damage. In addition, IL1RAP played a positive role in activating p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.


title: Validation of the British Society of Thoracic Imaging guidelines for COVID-19 chest radiograph reporting

text: Abstract Aim To validate the British Society of Thoracic Imaging issued guidelines for the categorisation of chest radiographs for coronavirus disease 2019 (COVID-19) reporting regarding reproducibility amongst radiologists and diagnostic performance. Materials and methods Chest radiographs from 50 patients with COVID-19, and 50 control patients with symptoms consistent with COVID-19 from prior to the emergence of the novel coronavirus were assessed by seven consultant radiologists with regards to the British Society of Thoracic Imaging guidelines. Results The findings show excellent specificity (100%) and moderate sensitivity (44%) for guideline-defined Classic/Probable COVID-19, and substantial interobserver agreement (Fleiss’ k=0.61). Fair agreement was observed for the “Indeterminate for COVID-19” (k=0.23), and “Non-COVID-19” (k=0.37) categories; furthermore, the sensitivity (0.26 and 0.14 respectively) and specificity (0.76, 0.80) of these categories for COVID-19 were not significantly different (McNemar’s test p=0.18 and p=0.67). Conclusion An amalgamation of the categories of “Indeterminate for COVID-19” and “Non-COVID-19” into a single “not classic of COVID-19” classification would improve interobserver agreement, encompass patients with a similar probability of COVID-19, and remove the possibility of labelling patients with COVID-19 as “Non-COVID-19”, which is the presenting radiographic appearance in a significant minority (14%) of patients.


title: Accessory proteins of SARS-CoV and other coronaviruses

text: Abstract The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus–host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses” (see Introduction by Hilgenfeld and Peiris (2013)).


title: Pathological and Microbiological Studies on Pneumonic Lungs from Danish Calves

text: During 1 year, the association between microbiological and pathological findings in 72 lungs from calves submitted to the Danish Veterinary Laboratory for diagnostic purposes was studied. All cases were evaluated pathologically and bacteriologically, whereas only 68 cases were examined for the presence of bovine respiratory syncytial virus (BRSV), parainfluenza‐3 virus (PI‐3 virus) and bovine coronavirus, 62 cases for bovine viral diarrhoea virus (BVD), 45 cases for bovine adenovirus and 51 cases for mycoplasmas. Based on histopathological examination, the cases were diagnosed as fibrinous and/or necrotizing bronchopneumonia, suppurative bronchopneumonia, embolic pneumonia and others. The diagnoses were based on the dominating and most severe lesions in each lung. Haemophilus somnus, Pasteurella multocida, Actinomyces pyogenes, P. haemolytica and BRSV were the most commonly found bacterial and viral lung pathogens, respectively. Pasteurella spp. and H. somnus were often associated with the more severe fibrino‐necrotizing type of bronchopneumonia, whereas BRSV was primarily detected in cases of suppurative bronchopneumonia. Mycoplasma bovis was isolated from one case only, whereas M. dispar, M. bovirhinis and Ureaplasma diversum were present, often concomitantly, in the majority of cases. Aspergillus fumigatus was isolated from one case.


title: Antioxidant and antiviral activities of lipophilic epigallocatechin gallate (EGCG) derivatives

text: Abstract The water soluble green tea polyphenol epigallocatechin gallate (EGCG) was lipophilised by esterification with different fatty acids for expanded applications. Four lipophilic ester derivatives of EGCG, namely EGCG-O-tetrastearate, EGCG-O-tetraeicosapentaenoate, EGCG-O-tetradocosahexaenoate, and EGCG-O-octabutyrate, were prepared and evaluated for their antioxidant and antiviral activities in vitro. Incorporation of fatty acids, especially the long chain polyunsaturated fatty acids (PUFA), into EGCG resulted in increased peroxyl radical scavenging activity, as measured by ORAC (oxygen radical absorbance capacity) assay, and metal chelation capacity. However, the esters exhibited decreased reducing power. Antiviral activities of EGCG derivatives were remarkably higher than the parent EGCG molecule, which showed relatively weak effects. The EGCG–PUFA esters were 1700-fold more effective in inhibiting hepatitis C virus (HCV) protease than the positive control embelin. The derivatives also acted as α-glucosidase inhibitors, suggesting their potential in anti-HIV (human immunodeficiency virus) treatment. The results suggest that ester derivatives of EGCG with improved bioactivities may serve as excellent functional food ingredients and natural health products. Moreover, the omega-3 PUFA in the derivatives may also render additional or synergistic health benefits.


title: Chapter 3 Biological HRPs in wastewater

text: Abstract Biological high-risk pollutants (HRPs) have become a serious threat to human health worldwide, and wastewater is one of the major sources of them in a natural environment. Despite the long history of wastewater research, comprehensive understanding of the role and behavior of HRPs during wastewater treatment is still limited owing to the complexity of the community. In recent decades, the rapid development of molecular tools, especially the wide application of next generation sequencing technologies, helps to unravel the community composition, structure, and dynamic variation in wastewater. Overall, this chapter mainly focuses on biological HRPs, including bacteria, viruses, protozoa, helminth, biotoxins, antibiotic resistance genes and antibiotic resistant bacteria in wastewater. The characteristics, classification, fates, functions, and health implications of these HRPs are introduced in detail. Moreover, the biogeography of HRPs is a research hotspot in recent years, and available information is also summarized in this chapter. Finally, we also propose the future research needs of HRPs in wastewater after the comprehensive summary of the existing research reports. This chapter is wished to be helpful for beginners to quickly understand the biological HRPs in wastewater.


docid: vgnxhksv

title: Crystal Structures Reveal an Induced-fit Binding of a Substrate-like Aza-peptide Epoxide to SARS Coronavirus Main Peptidase

text: Abstract The SARS coronavirus main peptidase (SARS-CoV Mpro) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-SARS agents. Here, we report the crystal structure of Mpro at a resolution of 1.82 Å, in space group P21 at pH 6.0. In contrast to the previously reported structure of Mpro in the same space group at the same pH, the active sites and the S1 specificity pockets of both protomers in the structure of Mpro reported here are in the catalytically competent conformation, suggesting their conformational flexibility. We report two crystal structures of Mpro having an additional Ala at the N terminus of each protomer (M+A(-1) pro), both at a resolution of 2.00 Å, in space group P43212: one unbound and one bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the active sites and the S1 specificity pockets of both protomers of M+A(-1) pro are observed in a collapsed (catalytically incompetent) conformation; whereas they are in an open (catalytically competent) conformation in the APE-bound form. The observed conformational flexibility of the active sites and the S1 specificity pockets suggests that these parts of Mpro exist in dynamic equilibrium. The structural data further suggest that the binding of APE to Mpro follows an induced-fit model. The substrate likely also binds in an induced-fit manner in a process that may help drive the catalytic cycle.


title: Turning Up Your Nose for a Flaviviral Encephalitis Cure

text: siRNA approaches have demonstrated promise in treating viral infections in animal models, but poor delivery limits clinical application. In this issue of Cell Host & Microbe, Beloor et al. (2018) report that nose-to-brain delivery of viral-targeted siRNA cures mice from West Nile virus encephalitis, with potential implications for human infection.


title: The broad spectrum of dermatological manifestations in COVID‐19. Clinical and histopathological features learned from a series of 34 cases

text: Since the outbreak of Coronavirus Disease (COVID‐19) pandemic began in Europe, a plethora of cutaneous manifestations have been related to this infection(1,2). However, their underlying mechanism and prognostic relevance remain unclear. Thus, we collected data from all COVID‐19 cases presenting with skin manifestations in our hospital in Madrid during one month.


title: Genetic characteristics and analysis of a novel rotavirus G3P[22] identified in diarrheic feces of Korean rabbit

text: Abstract Group A rotaviruses (RVAs) are important gastroenteric pathogens that infect humans and animals. This study aimed to analyze the complete genome sequence, i.e., 11 genome segments of the lapine rotavirus (LRV) identified in the intestine of a dead rabbit in the Republic of Korea (ROK) and to describe the genetic relationships between this lapine isolate [RVA/Rabbit-wt/KOR/Rab1404/2014/G3P[22] (Rab1404)] and other lapine isolates/strains. Rab1404 possessed the following genotype constellation: G3-P[22]-I2-R3-C3-M3-A9-N2-T3-E3-H3. The P[22] genotype was found to originate from rabbits and was for the first time identified in the ROK. Phylogenetic analysis showed that Rab1404 possessed VP1-3 and VP7 genes, which were closely related to those of the bat strain LZHP2; NSP1-4 genes, which were closely related to those of the simian strain RRV; and VP4, VP6, and NSP5 genes, which were closely related to the genes obtained from other rabbits. Interestingly, a close relationship between Rab1404 and simian RVA strain RVA/Simian-tc/USA/RRV/1975/G3P[3] for 8 gene segments was observed. RRV is believed to be a reassortant between bovine-like RVA strain and canine/feline RVA strains. Rab1404 and canine/feline RVAs shared the genes encoding VP1, VP3, VP7, NSP3, and NSP4. Additionally, the genome segments VP6 (I2), NSP1 (N2), and NSP5 (H3) of Rab1404 were closely related to those of bovine RVAs. This is the first report describing the complete genome sequence of an LRV detected in the ROK. These results indicate that Rab1404 could be a result of interspecies transmission, possibly through multiple reassortment events in the strains of various animal species and the subsequent transmission of the virus to a rabbit. Additional studies are required to determine the evolutionary source and to identify possible reservoirs of RVAs in nature.


title: Linking Emergency Preparedness and Health Care Worker Vaccination Against Influenza: A Novel Approach

text: Article-at-a-Glance Background Health care workers (HCWs) can acquire and transmit influenza to their patients and coworkers, even while asymptomatic. The U.S. Healthy People 2010 initiative set a national goal of 60% coverage for HCW influenza vaccination by 2010. Yet vaccination rates remain low. In the 2008–2009 influenza season, Flushing Hospital Medical Center (FHMC; New York) adopted a “push/pull” point-of-dispensing (POD) vaccination model that was derived from emergency preparedness planning for mass vaccination and/or prophylaxis to respond to an infectious disease outbreak, whether occurring naturally or due to bioterrorism. Launch of the HCW Vaccination Program In mid-September 2008, a two-week HCW vaccination program was launched using a sequential POD approach. In Push POD, teams assigned to specific patient units educated all HCWs about influenza vaccination and offered on-site vaccination; vaccinated HCWs received a 2009 identification (ID) validation sticker. In Pull POD, HCWs could enter the hospital only through one entrance; all other employee entrances were “locked down.” A 2009 ID validation sticker was required for entry and to punch in for duty. Employees without the new validation sticker were directed to a nearby vaccination team. After the Push/Pull POD was completed, the employee vaccination drive at FHMC was continued for the remainder of the influenza season by the Employee Health Service. Results Using this model, in two days 72% of the employees were reached, with 54% of those reached accepting vaccination. Conclusions This model provides a novel approach for institutions to improve their HCW influenza vaccination rates within a limited period through exercising emergency preparedness plans for infectious disease outbreaks.


title: Evaluation of the tuberculosis programme in Ningxia Hui Autonomous region, the People’s Republic of China: a retrospective case study

text: BACKGROUND: Tuberculosis is a devastating disease due to its rapid transmission and high rate of mortality. Ningxia Hui Autonomous Region (NHAR), located in the North-west, is one of the poorest provinces in China and national surveys have shown TB has been hyper endemic in NHAR for several decades. As no active surveys had been undertaken since the initiation of the DOTS control program across all of NHAR. METHODS: A retrospective study was undertaken of all clinical records of TB patients registered from January 2005 to September 2009. Poisson regression was performed to investigate the change in incidence over time and accounted for age, sex and county. Length of time on treatment, disease severity and patient delay were assessed by county. RESULTS: More than 30% of patients had been on treatment for over 12 months and 10% for over 3 years, reflecting drug-resistance or failure of DOTS. More than 93% of patients had grade III disease at time of diagnosis and >15% of patients had severe disease grade IV-V in some NHAR counties. Further, 8.8% of patients were not diagnosed for over 6 months from the onset of symptoms; this was as high as 20% in some counties. The reported incidence of TB is most likely grossly underestimated and the data indicate TB is a major public health concern in NHAR. CONCLUSIONS: It is clear that active surveillance is necessary to determine the full extent of the burden of TB in NHAR. New control and treatment strategies for TB are required that increase awareness in the health-care system and at the individual and community level.


title: In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel

text: Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with ‘severe acute respiratory syndrome’ (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human ‘SARS-CoV2 E’ protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human ‘SARS-CoV2 E’ protein gets reduced, this, in turn, inhibits the function of the ‘SARS-CoV2 E’ protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as ‘Lipinski’s Rule of 5s’, they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation. Communicated by Ramaswamy H. Sarma


Activation of cytotoxic T cell population and inversion of CD4:CD8 ratio as manifestations of cellular immune response in SARS-COV-2 infection


title: Confronting Zoonoses, Linking Human and Veterinary Medicine

text: Many of the emerging infectious diseases, including those caused by bioterrorist agents, are zoonoses. Since zoonoses can infect both animals and humans, the medical and veterinary communities should work closely together in clinical, public health, and research settings. In the clinical setting, input from both professions would improve assessments of the risk-benefit ratios of pet ownership, particularly for pet owners who are immunocompromised. In public health, human and animal disease surveillance systems are important in tracking and controlling zoonoses such as avian influenza virus, West Nile virus, and foodborne pathogens. Comparative medicine is the study of disease processes across species, including humans. Physician and veterinarian comparative medicine research teams should be promoted and encouraged to study zoonotic agent-host interactions. These efforts would increase our understanding of how zoonoses expand their host range and would, ultimately, improve prevention and control strategies.


title: Loop-mediated isothermal amplification establishment for detection of pseudorabies virus

text: Abstract A rapid, convenient and reliable pseudorabies virus (PRV) detection system was developed by using the loop-mediated isothermal amplification (LAMP) method. Six special primers were designed successfully based on the PRV DNA-binding protein (DBP) gene. The assay was optimized to amplify PRV DNA by incubation at 63°C for 1h. The LAMP products had a ladder-like pattern of bands from 188bp when electrophoresed on an agarose gel and its specificity was confirmed by digestion with Hinc II enzyme. Two naked-eye detection methods were developed for use in the field. The detection limit of the LAMP assay was found to be 10fg DNA sample which was 100–1000-fold higher than that of PCR. By using DNA (or cDNA) samples extracted from three different PRV strains and six other viruses known to be related genetically to PRV or to cause similar clinical signals in pig, the system was identified to amplify only the PRV DNA. A comparison between the LAMP and PCR assay using five clinical samples showed good correlation.


title: Deadly encounters in Australia Harriet A Washington Dead

text: Unknown


docid: kywhulpc

title: A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells

text: BACKGROUND: The Janus kinase (Jak) and signaling transducer activator of transcription (Stat) pathway mediates the signaling of genes required for cellular development and homeostasis. To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. RESULTS: Concurrent SAV3 infection with type I IFN treatment of TO-cells suppressed SAV3 structural protein (SP) expression by 2log(10) at 2 days post infection compared to SAV3 infection without IFN treatment which paved way to evaluating the impact of type I IFN on expression of Jak/stat pathway genes in SAV3 infected TO-cells. In the absence of type I IFN treatment, SAV3 downregulated several Jak/stat pathway genes that included type I and II receptor genes, Jak2, tyrosine kinase 2 (Tyk2), Stat3 and Stat5 pointing to possible failure to activate the Jak/stat signaling pathway and inhibition of signal transducers caused by SAV3 infection. Although the suppressor of cytokine signaling (SOCS) genes 1 and 3 were upregulated in the IFN treated cells, only SOCS3 was downregulated in the SAV3 infected cells which points to inhibition of SOCS3 by SAV3 infection in TO-cells. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Overall, we have shown that combining de novo assembly with pathway based transcriptome analyses provides a contextual approach to understanding the molecular networks of genes that form the Jak/stat pathway in TO-cells infected by SAV3.


title: Bronchoalveolar lavage to evaluate new pulmonary infiltrates in allogeneic hematopoietic stem cell transplant recipients: impact on antimicrobial optimization

text: Summary Background Pulmonary complications cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (AHSCT). Bronchoscopy with targeted bronchoalveolar lavage (BAL) is often used in AHSCT patients with suspected lower respiratory tract infection (LRTI) to help guide management. Aim To evaluate how positive BAL results change antimicrobial management of AHSCT recipients with suspected LRTI. Methods We performed a retrospective review of BAL results from January 2014 to July 2016 for 54 AHSCT recipients. A positive BAL was determined by culture, multiplex polymerase chain reaction (PCR), Aspergillus galactomannan antigen (AGA), and cytology. Findings BAL was positive for infectious etiologies in 63%, and antimicrobials were adjusted in 48/54 (89%) of patients. Antibacterial escalation was predicted by a positive BAL bacterial culture (OR 7.61, P=0.017). Antibiotic de-escalation was more likely with an elevated AGA (OR 3.86, P=0.035). Antiviral initiation was more likely with positive BAL multiplex PCR (OR 17.33, P=0.010). Antifungals were more likely to be escalated or changed with an elevated AGA (OR 4.33, P=0.020). The patients with a negative BAL were more likely to be started on steroids (OR 0.19, P= 0.043). Conclusions BAL was helpful to determine the etiology of pulmonary complications and optimize antimicrobials. The addition of AGA and multiplex PCR to standard BAL significantly impacted de-escalating antibiotics and adjusting antifungals to provide adequate coverage. The association with an elevated AGA with antibacterial de-escalation highlights a new role for BAL in antimicrobial optimization.


title: Cytokine Release Syndrome Grade as a Predictive Marker for Infections in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Chimeric Antigen Receptor T Cells

text: BACKGROUND: Chimeric antigen receptor (CAR)–modified T cells that target the CD19 antigen present a novel promising therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia (B-ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant noninfectious complications of CD19 CAR T-cell therapy, infections associated with this treatment modality have not been well documented. METHODS: We analyzed infectious complications that followed CD19 CAR T-cell therapy in 53 adult patients with relapsed B-ALL enrolled in a phase I clinical trial at Memorial Sloan Kettering Cancer Center (NCT01044069). RESULTS: Overall, 22 patients (42%) experienced 26 infections (17 bacterial, 4 fungal, and 5 viral) within the first 30 days of CAR T-cell infusion. In 10 of 32 (31%) patients in whom complete remission was achieved, 15 infections developed between days 31 and 180; the majority of these late infections were due to respiratory viruses. In general, bacterial, fungal, and viral infections were detected at a median of 18, 23, and 48 days, respectively, after CAR T-cell infusion. CRS grade 3 or higher was independently associated with increased risk of subsequent infection (adjusted hazard ratio [HR], 2.67; P = .05) and in particular with bloodstream infection (adjusted HR, 19.97; P < .001). Three of 53 patients (6%) died of an infection-related cause. CONCLUSIONS: Infections in adult patients with relapsed B-ALL are common after CD19 CAR T-cell therapy. Understanding the infectious complications that are temporally coincident with CD19 CAR T-cell therapy is critical for developing effective prophylactic and other supportive care measures to improve clinical outcomes. CLINICAL TRIALS REGISTRATION: NCT01044069.


title: Long‐term outcome of cats with acquired myasthenia gravis without evidence of a cranial mediastinal mass

text: BACKGROUND: Acquired myasthenia gravis (AMG) is increasingly recognized in cats, yet information regarding the natural history of the disease, treatment, and outcome including occurrence of immune and spontaneous remission remains limited. OBJECTIVE: To determine the long‐term outcome of cats with AMG without evidence of a cranial mediastinal mass (CMM). ANIMALS: Eight cats diagnosed with AMG without evidence of a CMM. METHODS: Retrospective case series. The medical records of cats diagnosed with AMG between 2005 and 2018 from 2 veterinary referral hospitals were reviewed for inclusion. Inclusion criteria consisted of a diagnosis of AMG, thoracic imaging, serum biochemistry including measurement of creatine kinase, and a CBC. Exclusion criteria were the presence of an identifiable CMM, or administration of methimazole or carbimazole. RESULTS: All cats had an excellent long‐term outcome, achieving immune remission within 6 months of diagnosis, including 4 cats that did not receive any treatment and whose natural course of disease involved spontaneous remission. Clinical presentation was heterogeneous, and skeletal muscle weakness and fatigability induced or exacerbated by the wheelbarrow exercise stress test were the most consistent abnormalities associated with AMG. CONCLUSION AND CLINICAL IMPORTANCE: Cats diagnosed with AMG without evidence a CMM have a favorable outcome and frequently achieve immune remission. Moreover, the natural history of AMG in cats includes spontaneous remission when there is no evidence of a CMM. Attempting to rule out the presence of a CMM therefore refines prognosis, and treatment is not always necessary in this disease population.


title: Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosis

text: Background/Aims Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1–7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1–7) in the bile duct ligated (BDL) rat. Methods BDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance. Results Hepatic ACE2 gene and activity (P <0.0005), plasma angiotensin-(1–7) (P <0.0005) and Mas receptor expression (P <0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1–7) (P <0.05) from angiotensin II and this was augmented (P <0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1–7) had no effect on portal resistance. Conclusions RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1–7) leading to increased circulating angiotensin-(1–7). These results support the presence of an ACE2-angiotensin-(1–7)-Mas axis in liver injury which may counteract the effects of angiotensin II.


docid: ltjurdrq

title: Food and Waterborne Illnesses

text: There are many different biological, chemical, or radiological agents that when added to food can result in many different types of illness. Some may be rapidly fatal; others require long-term exposure to result in illness. Some lead to short-term illness and others result in long-term complications. The universe of such agents and situations is enormous. This article summarizes some of the principal foodborne microbiological agents that clinicians and those involved with public health have to deal with. While the range of agents is broad and the list is long there are several basic mechanisms such as ingestion of preformed toxins or toxin production once a microbe is present in the intestine that facilitate sorting these agents into some logical framework. However, at the end of the day it is always key to think about ingested agents as a cause for illness, whether that illness be confined to the intestinal system or more systemic. In principle all foodborne illness is preventable and of the key messages to consumers and health care professionals is to know if you or your patient is at greater risk from foodborne illness. If one is dealing with an ‘at risk’ patient, it is important they be educated on what foods to avoid and what precautions to take to minimize the likelihood of acquiring a foodborne illness. While treating most foodborne illness is straightforward, prevention is clearly the path of choice.


title: Supporting Innovative Person-Centred Care in Financially Constrained Environments: The WE CARE Exploratory Health Laboratory Evaluation Strategy

text: The COST CARES project aims to support healthcare cost containment and improve healthcare quality across Europe by developing the research and development necessary for person-centred care (PCC) and health promotion. This paper presents an overview evaluation strategy for testing ‘Exploratory Health Laboratories’ to deliver these aims. Our strategy is theory driven and evidence based, and developed through a multi-disciplinary and European-wide team. Specifically, we define the key approach and essential criteria necessary to evaluate initial testing, and on-going large-scale implementation with a core set of accompanying methods (metrics, models, and measurements). This paper also outlines the enabling mechanisms that support the development of the “Health Labs” towards innovative models of ethically grounded and evidenced-based PCC.


title: The peripheral blood immune cell profile in a teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia

text: A teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia was hospitalized and recovered in 15 days. The immunophenotyping analysis of peripheral blood cells was performed in two time points: the first was 1 month before (pre-infection) while the second was during COVID-19 pneumonia (infection). At the infection time point, no differences in the percentages of immune activation and immunesenescence of CD4+ and CD8+ T-cells were observed compared to the pre-infection time point. Our evaluation seems to confirm that teriflunomide control T-cells immune activation and immunosenescence suggesting that teriflunomide should not be discontinued in MS patients with an active COVID-19 pneumonia.


title: Platform technologies for modern vaccine manufacturing

text: Abstract Improved understanding of antigenic components and their interaction with the immune system, as supported by computational tools, permits a sophisticated approach to modern vaccine design. Vaccine platforms provide an effective tool by which strategically designed peptide and protein antigens are modularized to enhance their immunogenicity. These modular vaccine platforms can overcome issues faced by traditional vaccine manufacturing and have the potential to generate safe vaccines, rapidly and at a low cost. This review introduces two promising platforms based on virus-like particle and liposome, and discusses the methodologies and challenges.


title: European citizens’ opinions on immunisation

text: As part of a larger study exploring how European citizens’ balance issues of public and private interest and the extent to which they are prepared to accept State intervention on a range of public health issues, focus group participants were asked whether childhood immunisation should be a matter of parental choice or State compulsion. The question was debated in 66 (of 96) focus groups held across 16 European countries in 2003. Discussions focused on the concept of risk, trust in health professionals and the State, upholding the status quo, fears over vaccine safety and perceptions of infectious disease as a ‘foreign threat’.


Hepatocellular Carcinoma (HCC) in the COVID‐19 era: Primetime for Stereotactic Body Radiotherapy and a lesson for the future?


title: Gripe A (H1N1)v pandémica en UCI: ¿qué hemos aprendido?

text: Resumen Las características de la gripe pandémica 2009 son diferentes de las de la gripe estacional. En Australia- Nueva Zelanda (ANZIC) se multiplicaron por 15 los ingresos en la unidad de cuidados intensivos (UCI) en el invierno austral. Se comparan las características de la serie española de los primeros ingresos en UCI en julio con las series publicadas en Canadá y ANZIC hasta octubre de 2009. A diferencia de lo observado en España, sólo la mitad de los ingresos en Canadá y ANZIC se debió a neumonía viral primaria, mientras que la neumonía bacteriana fue más frecuente en los primeros. En todas las series, los jóvenes, muchos de los cuales no tenían comorbilidad, fueron la población más afectada. La obesidad, la patología pulmonar crónica, el embarazo y la cardiopatía fueron las comorbilidades más frecuentes. El diagnóstico mediante rt-PCR puede presentar un 10% de falsos negativos. El shock y la insuficiencia renal aguda fueron más frecuentes en la serie española. El 10-30% de los afectados requieren ingreso a UCI y 6 de cada 10 ventilación mecánica (VM), con una alta frecuencia de fracaso de la ventilación no invasiva (75%). La mortalidad fue similar entre las series (14-25%), aunque mayor en los pacientes que requieren VM (30%). La administración precoz (< 48 h de inicio de los síntomas) de oseltamvir se ha asociado a una mejor evolución. Por ello, su administración precoz en pacientes con factores de riesgo, o en quienes aun sin ellos presentan signos de progresión clínica, podría reducir el ingreso en la UCI y la mortalidad. Abstract The characteristics of pandemic influenza 2009 differ from those of seasonal influenza. In Australia-New Zealand the number of admissions to the intensive care unit (ICU) increased by 15-fold in the southern winter. We compared the characteristics of the Spanish series of the first ICU admissions in July with those of series published in Canada and Australia-New Zealand up to October 2009. Unlike the situation in Spain, only half the admissions in Canada and Australia-New Zealand were due to primary viral pneumonia but bacterial pneumonia was much more frequent. In all series, young people, many of whom had no comborbidities, were the most frequently affected population. The most common comorbidities were obesity, chronic pulmonary disease, pregnancy and heart disease. Diagnosis through reverse-transcriptase polymerase chain reaction can have a false-negative rate of 10%. Shock and acute renal insufficiency were more frequent in the Spanish series. A total of 10-30% of patients required ICU admission and 6 of 10 patients required mechanical ventilation with a high frequency of failure of non-invasive ventilation (75%). Mortality was similar among the series (14-25%) but was higher in patients requiring mechanical ventilation (30%). Early oseltamivir administration (< 48h after symptom onset) has been associated with better outcome. Therefore, early administration of this drug in patients with risk factors or those who, although free from risk factors, show clinical progression, could reduce ICU admissions and mortality.


Preliminar detection of lung hypoperfusion in discharged Covid-19 patients during recovery


title: Spreading of infections on random graphs: A percolation-type model for COVID-19

text: We introduce an epidemic spreading model on a network using concepts from percolation theory. The model is motivated by discussing the standard SIR model, with extensions to describe effects of lockdowns within a population. The underlying ideas and behaviour of the lattice model, implemented using the same lockdown scheme as for the SIR scheme, are discussed in detail and illustrated with extensive simulations. A comparison between both models is presented for the case of COVID-19 data from the USA. Both fits to the empirical data are very good, but some differences emerge between the two approaches which indicate the usefulness of having an alternative approach to the widespread SIR model.


title: Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review

text: Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5–13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000–295 000], enteropathogenic E. coli 79 000 (UR 31 000–146 000), calicivirus 71 000 (UR 39 000–113 000), and enterotoxigenic E. coli 42 000 (UR 20 000–76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world.


title: Seasonal synchrony in incidences of common infectious diagnoses in early childhood among neighbouring regions

text: Summary Objectives Information on seasonal synchrony of influenza activity between neighbouring regions has been found useful for planning infection control measures. Seasonal synchrony of other infectious diseases is less known. We describe the seasonality and seasonal synchrony of three common childhood infectious diagnoses among three regions in Taiwan. Methods A large, nationally representative sample of young children (N =128 651, age 0–4 years) was used to estimate the monthly incidences of acute respiratory infection, acute intestinal infection, and herpangina and hand, foot, and mouth disease (HFMD) in three regions of Taiwan between 2000 and 2005. Seasonality of monthly incidences was indicated by year-on-year intra-class correlations (ICCs). Between-region ICCs were used to describe seasonal synchrony of incidences between regions. Results We found evidence of seasonality in all three infectious diagnoses (p <0.05). Seasonal synchrony among the three regions was highest for acute respiratory infection (between-region ICC 0.91, 95% confidence interval (CI) 0.87–0.94), followed by herpangina and HFMD (between-region ICC 0.85, 95% CI 0.80–0.90), and acute intestinal infection (between-region ICC 0.69, 95% CI 0.59–0.79). Conclusions We found strong evidence of seasonal synchrony in the incidences of acute respiratory infection, acute intestinal infection, and herpangina and HFMD between three neighbouring regions of Taiwan. An understanding of these disease patterns may inform future infection control measures.


title: Parasites reveal movement of bats between the New and Old Worlds

text: Abstract The global distribution of bat taxa indicates that the Atlantic and Pacific Oceans are effective barriers to movement between the Old and New Worlds. For instance, one of the major suborders, Yinpterochiroptera, has an exclusively Old World distribution, and within the other, Yangochiroptera, no species and only five genera are common to both. However, as bats are sometimes blown out to sea, and have colonised isolated islands, occasional natural movement between the New and Old Worlds does appear to be possible. Here we identify new genotypes of a blood parasite, Trypanosoma dionisii, in Old World bats that are closely related to South American strains. Using highly conservative calibration points, divergence of Old and New World strains is estimated to have occurred 3.2–5.0million years ago (MYA), depending on the method used (upper 95% CL for maximum time 11.4MYA). The true date of divergence is likely to be considerably more recent. These results demonstrate that taxon-specific parasites can indicate historical movements of their hosts, even where their hosts may have left no lasting phylogenetic footprint.


title: Evolutionary analysis of rabies virus isolates from Guangxi Province of southern China

text: BACKGROUND: Rabies is a severe epidemic in Guangxi province, China, with hundreds of deaths occurring each year. In the past six decades, rabies has emerged three times in Guangxi, and the province has reported the largest number of rabies cases in China. The domestic dog is the principal vector for rabies, and 95% of human cases are associated with transmission from dogs. RESULTS: To understand the genetic relationship between street rabies virus (RABV) from Guangxi, genetic diversity analysis was performed using RABV isolates collected between 1999 and 2012. The N gene of 42 RABV isolates, and the P and M genes, as well as fragments of the 3′ terminus (L(1–680)) and the polymerase activity module of the L gene (L(pam)) of 36 RABV isolates were sequenced. In addition, whole genome sequencing was performed for 5 RABV isolates. There was evidence of topological discrepancy in the phylogenetic trees based on different genes of the RABV isolates. Amino acid variation of the deduced N protein exhibited different patterns to those obtained from the P and M proteins reported here, and the previously reported G protein (Tang H. et al., PLoS Negl Trop Dis, 8(10): e3114, 2014), and L(1–680) and L(pam). These RABV isolates were divided into three main branches against fixed strains. CONCLUSION: RABV is prevalent in Guangxi province and strains collected over the last two decades belong mainly to three groups (I, II, III). These RABV isolates reveal genetic diversity. Individual RABV genes from Guangxi exhibit different evolutionary characteristics. The results will have benefits for continuing comprehensive rabies surveillance, prevention and control in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1514-0) contains supplementary material, which is available to authorized users.


title: Anti-inflammatory effect of Houttuynia cordata injection

text: Abstract Houttuynia cordata (Saururaceae) injection (HCI) is a traditional Chinese medicine used in China. It was chosen as one of eight types of traditional Chinese medicine that play a unique role in severe acute respiratory syndrome (SARS) owing to the effect of curbing inflammation. In order to validate this plausible anti-inflammatory property, the chemical composition of HCI has been analysed by GC/MS, 22 components were identified, and the inflammation induced by carrageenan in the rat pleurisy model and by xylene in the mice ear edema model was adopted to study the anti-inflammatory activity of HCI. Injection of carrageenan into the pleural cavity elicited an acute inflammatory response characterized by protein rich fluid accumulation and leukocyte infiltration in the pleural cavity. The peak inflammatory response was obtained at 24h when the fluid volume, protein concentration, C-reactive protein and cell infiltration were maximums. The results showed that these parameters were attenuated by HCI at any dose and touched bottom at dose of 0.54ml/100g, although less strong than dexamethasone. This drug was also effective in inhibiting xylene induced ear edema, and the percentage of inhibition came to 50% at dose of 80μl/20g. The results clearly indicate that HCI have anti-inflammatory activity.


title: Genetic diversity of bats coronaviruses in the Atlantic Forest hotspot biome, Brazil

text: Abstract Bats are notorious reservoirs of genetically-diverse and high-profile pathogens, and are playing crucial roles in the emergence and re-emergence of viruses, both in human and in animals. In this report, we identified and characterized previously unknown and diverse genetic clusters of bat coronaviruses in the Atlantic Forest Biome, Brazil. These results highlight the virus richness of bats and their possible roles in the public health.


title: Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

text: Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes > 2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections. Despite their limited application in the field, GWASs have provided valuable insights by pinpointing associations to both innate and adaptive immune response loci, as well as novel unexpected risk factors for infection susceptibility. Herein, we discuss some issues and caveats of GWASs for infectious diseases, we review the most recent findings ensuing from these studies, and we provide a brief summary of selected GWASs for infections in non-human mammals. We conclude that, although the general trend in the field of complex traits is to shift from GWAS to next-generation sequencing, important knowledge on infectious disease-related traits can be still gained by GWASs, especially for those conditions that have never been investigated using this approach. We suggest that future studies will benefit from the leveraging of information from the host's and pathogen's genomes, as well as from the exploration of models that incorporate heterogeneity across populations and phenotypes. Interactions within HLA genes or among HLA variants and polymorphisms located outside the major histocompatibility complex may also play an important role in shaping the susceptibility and response to invading pathogens.


title: Extinction and emergence of genomic haplotypes during the evolution of Avian coronavirus in chicken embryos

text: Avian coronavirus (AvCoV) is ubiquitously present on poultry as a multitude of virus lineages. Studies on AvCoV phenotypic traits are dependent on the isolation of field strains in chicken embryonated eggs, but the mutant spectrum on each isolate is not considered. This manuscript reports the previously unknown HTS (high throughput sequencing)-based complete genome haplotyping of AvCoV isolates after passages of two field strains in chicken embryonated eggs. For the first and third passages of strain 23/2013, virus loads were 6.699 log copies/ μL and 6 log copies/ μL and, for 38/2013, 5.699 log copies/μL and 2.699 log copies/μL of reaction, respectively. The first passage of strain 23/2013 contained no variant haplotype, while, for the third passage, five putative variant haplotypes were found, with > 99.9% full genome identity with each other and with the dominant genome. Regarding strain 38/2013, five variant haplotypes were found for the first passage, with > 99.9% full genome identity with each other and with the dominant genome, and a single variant haplotype was found. Extinction and emergence of haplotypes with polymorphisms in genes involved in receptor binding and regulation of RNA synthesis were observed, suggesting that phenotypic traits of AvCoV isolates are a result of their mutant spectrum.


‘Ring of fire’ appearance in COVID-19 pneumonia


Mind the App—Considerations on the Ethical Risks of COVID-19 Apps


Deficiencies in the designs and interventions of COVID-19 clinical trials


title: Development and evaluation of an efficient 3′-noncoding region based SARS coronavirus (SARS-CoV) RT-PCR assay for detection of SARS-CoV infections

text: Abstract The severe acute respiratory syndrome (SARS) epidemic originating from China in 2002 was caused by a previously uncharacterized coronavirus that could be identified by specific RT-PCR amplification. Efforts to control future SARS outbreaks depend on the accurate and early identification of SARS-CoV infected patients. A real-time fluorogenic RT-PCR assay based on the 3′-noncoding region (3′-NCR) of SARS-CoV genome was developed as a quantitative SARS diagnostic tool. The ideal amplification efficiency of a sensitive SARS-CoV RT-PCR assay should yield an E value (PCR product concentration increase per amplification cycle) equal to 2.0. It was demonstrated that the 3′-NCR SARS-CoV based RT-PCR reactions could be formulated to reach excellent E values of 1.81, or 91% amplification efficacy. The SARS-CoV cDNA preparations derived from viral RNA extract and the cloned recombinant plasmid both exhibit the identical amplification characteristics, i.e. amplification efficacy using the same PCR formulation developed in this study. The viral genomic copy (or genomic equivalences, GE) per infectious unit (GE/pfu) of SARS-CoV used in this study was also established to be approximate 1200–1600:1. The assay’s detection sensitivity could reach 0.005pfu or 6–8GE per assay. It was preliminarily demonstrated that the assay could efficiently detect SARS-CoV from clinical specimens of SARS probable and suspected patients identified in Taiwan. The 3′-NCR based SARS-CoV assay demonstrated 100% diagnostic specificity testing samples of patients with acute respiratory disease from a non-SARS epidemic region.


title: Biochemical Analysis of Coronavirus Spike Glycoprotein Conformational Intermediates during Membrane Fusion

text: A fusion protein expressed on the surface of enveloped viruses mediates fusion of the viral and cellular membranes to facilitate virus infection. Pre- and postfusion structures of viral fusion proteins have been characterized, but conformational changes between them remain poorly understood. Here, we examined the intermediate conformation of the murine coronavirus fusion protein, called the spike protein, which must be cleaved by a cellular protease following receptor binding. Western blot analysis of protease digestion products revealed that two subunits (67 and 69 kDa) are produced from a single spike protein (180 kDa). These two subunits were considered to be by-products derived from conformational changes and were useful for probing the intermediate conformation of the spike protein. Interaction with a heptad repeat (HR) peptide revealed that these subunits adopt packed and unpacked conformations, respectively, and two-dimensional electrophoresis revealed a trimeric assembly. Based on biochemical observations, we propose an asymmetric trimer model for the intermediate structure of the spike protein. Receptor binding induces the membrane-binding potential of the trimer, in which at least one HR motif forms a packed-hairpin structure, while membrane fusion subunits are covered by the receptor-binding subunit, thereby preventing the spike protein from forming the typical homotrimeric prehairpin structure predicted by the current model of class I viral fusion protein. Subsequent proteolysis induces simultaneous packing of the remaining unpacked HRs upon assembly of three HRs at the central axis to generate a six-helix bundle. Our model proposes a key mechanism for membrane fusion of enveloped viruses. IMPORTANCE Recent studies using single-particle cryo-electron microscopy (cryoEM) revealed the mechanism underlying activation of viral fusion protein at the priming stage. However, characterizing the subsequent triggering stage underpinning transition from pre- to postfusion structures is difficult because single-particle cryoEM excludes unstable structures that appear as heterogeneous shapes. Therefore, population-based biochemical analysis is needed to capture features of unstable proteins. Here, we analyzed protease digestion products of a coronavirus fusion protein during activation; their sizes appear to be affected directly by the conformational state. We propose a model for the viral fusion protein in the intermediate state, which involves a compact structure and conformational changes that overcome steric hindrance within the three fusion protein subunits.


title: Health care workers' perceptions of respiratory and gastrointestinal algorithms for patient management in emergency care settings

text: BACKGROUND: Patients with respiratory or gastrointestinal illness in emergency care settings are often not yet diagnosed but are at risk of transmitting disease. Infection control algorithms delineating a standard approach to patient management decrease risk of secondary exposure, but few articles document health care workers' (HCWs) perceptions as to their effectiveness and ease of implementation. METHODS: A cross-sectional survey approach was used to explore HCWs perceptions in 2 emergency departments of the current algorithms for management of potentially infectious respiratory and gastrointestinal illnesses. RESULTS: Surveys from 96 HCWs revealed that algorithms were perceived as invaluable in protecting staff, patients, and colleagues. Differences in self-reported compliance, clarity, and ease of implementation of the respiratory algorithm were noted between facilities, likely reflecting variation in the physical plant. Physicians scored significantly lower for compliance with the respiratory algorithm. CONCLUSION: Algorithms were perceived to offer a clear and consistent approach to patient management and protect HCWs in spite of environmental and resource limitations.


title: Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

text: Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs.