title: Synthesis and anti-HSV activity of tricyclic penciclovir and hydroxybutylguanine derivatives

text: Abstract A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R = 4-MeO-C6H4) displayed good inhibitory activity (HSV-1 EC50 1.5 μM, HSV-2 EC50 0.8 μM) and retained inhibitory activity in HSV-1 TK− cells (EC50 0.8 μM). Computational docking experiments supported the biological data observed and this preliminary study provides useful data for further development of tricyclic acyclic nucleoside derivatives with improved lipophilicity and retention of activity in HSV-1 TK deficient strains. Also, the new tricyclic derivatives were evaluated against a broad range of other DNA and RNA viruses, but were found to be inactive at subtoxic concentrations. In addition, weak to moderate cytostatic effect was observed for the new compounds.


title: Comparison of four new commercial serologic assays for determination of SARS-CoV-2 IgG

text: Abstract Background Facing the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for serological assays identifying individuals with past coronavirus disease 2019 (COVID-19). Study Design Our study is the first to compare four new commercially available assays using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR: the anti SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany), the EDI New Coronavirus COVID-19 IgG ELISA, (Epitope diagnostics (EDI), USA), the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Germany), and the SARS-CoV-2 Virachip IgG (Viramed, Germany). Results We found a sensitivity of 86.4%, 100%, 86.4%, and 77.3% and a specificity of 96,2%, 88,7%, 100%, and 100% for the Euroimmun assay, the EDI assay, the Mikrogen assay, and the Viramed assay, respectively. Conclusions Commercially available SARS-CoV-2 IgG assays have a sufficient specificity and sensitivity for identifying individuals with past SARS-CoV-2 infection.


title: The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015

text: BACKGROUND: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. CASE PRESENTATION: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. CONCLUSIONS: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.


title: Biocontainment in Gain-of-Function Infectious Disease Research

text: The discussion of H5N1 influenza virus gain-of-function research has focused chiefly on its risk-to-benefit ratio. Another key component of risk is the level of containment employed. Work is more expensive and less efficient when pursued at biosafety level 4 (BSL-4) than at BSL-3 or at BSL-3 as modified for work with agricultural pathogens (BSL-3-Ag). However, here too a risk-to-benefit ratio analysis is applicable. BSL-4 procedures mandate daily inspection of facilities and equipment, monitoring of personnel for signs and symptoms of disease, and logs of dates and times that personnel, equipment, supplies, and samples enter and exit containment. These measures are not required at BSL-3 or BSL-3-Ag. Given the implications of inadvertent or deliberate release of high-threat pathogens with pandemic potential, it is imperative that the World Health Organization establish strict criteria for biocontainment that can be fairly applied in the developing world, as well as in more economically developed countries.


title: Chapter Four The Roles of the Secreted Phospholipase A2 Gene Family in Immunology

text: Abstract Within the phospholipase A2 (PLA2) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA2 (sPLA2) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA2s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA2 enzymes, particularly cytosolic PLA2 (cPLA2α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA2s have remained a mystery over the last few decades. Recent studies employing mice gene-manipulated for individual sPLA2s, in combination with mass spectrometric lipidomics to identify their target substrates and products in vivo, have revealed their roles in diverse biological events, including immunity and associated disorders, through lipid mediator-dependent or -independent processes in given microenvironments. In this review, we summarize our current knowledge of the roles of sPLA2s in various immune responses and associated diseases.


title: Vets, Meds, and Zoonotic Threats

text: The fourth international conference on emerging zoonoses (September 18–21, Ames, Iowa, USA) brought together 180 scientists and healthcare specialists from 18 countries working to control diseases transmitted from animals to humans. The meeting took place under the auspices of the Center of Food Security and Public Health, USA, and the Institute for International Cooperation in Animal Biologics (a collaborating center of the World Animal Health Organisation [OIE]).


title: 12 Advances in Cancer Chemotherapeutic Drug Research in China

text: In this chapter, the history of cancer chemotherapy discipline in China is briefly reviewed. Some effective antitumor drugs discovered in China are introduced such as Gengshengmeisu (actinomycin K), hydroxycamptothecin, homoharringtonine, methoxysarcolysin, N-formyl sarcolysin, nitrocaphane, glyciphosphoramide, bimolane, sobuzoxane, Sb-71 (antimony ammonia triacetic acid), and so on. New inhibitors of topoisomerases I and II such as chimmitecan and salvicine are described in detail regarding to their chemistry, antitumor activity, mechanism of action, and clinical trial. A number of effective anticancer compounds including angiogenesis inhibitor pseudolaric acid B, EGFR inhibitor quinonazoline derivative BB, and others are presented. New results obtained in our institute on several series of derivatives of N-substituted-thiourea; 3,5-substituted indolin-2-one compounds; 3-nitroquinolines; and quercetin-3-O-amino acid-esters and triaminotriazine analogs related to their design, synthesis, and antitumor evaluation are also provided. Keywords cancer, chemotherapeutic, drug research, advances in China


docid: nqqwnmwc

title: Origin, evolution and innate immune control of simian foamy viruses in humans

text: Most viral pathogens that have emerged in humans have originated from various animal species. Emergence is a multistep process involving an initial spill-over of the infectious agent into single individuals and its subsequent dissemination into the human population. Similar to simian immunodeficiency viruses and simian T lymphotropic viruses, simian foamy viruses (SFV) are retroviruses that are widespread among non-human primates and can be transmitted to humans, giving rise to a persistent infection, which seems to be controlled in the case of SFV. In this review, we present current data on the discovery, cross-species transmission, and molecular evolution of SFV in human populations initially infected and thus at risk for zoonotic emergence.


The 10th Anniversary of Asia Pacific Allergy


title: Low-cost Double Protective Barrier for Intubating Patients amid COVID-19 Crisis

text: Supplemental Digital Content is available in the text.


title: COVID‐19 in Pakistan: Impact on global polio eradication initiative

text: A recent report reviewed the polio epidemiology in Pakistan 1 . Pakistan is currently showing a very high number of COVID-19 cases2 . The outbreak of COVID-19 has been known to cause by SARS-CoV-2, a novel coronavirus that emerged by the end of December 2019. This article is protected by copyright. All rights reserved.


title: Issues Relevant to the Adoption and Modification of Hospital Infection-Control Recommendations for Avian Influenza (H5N1 Infection) in Developing Countries

text: The reemergence of avian influenza (H5N1 infection) has heightened concern for a potential human influenza pandemic. Recommendations regarding preparation for a global avian influenza pandemic are available, and it is imperative that health care workers participate in preparedness planning and training. In developing countries, health care worker preparedness training should address the modes of avian influenza transmission and specify how to implement appropriate infection-control strategies to prevent and control the spread of avian influenza. We provide evidence for avian influenza transmission methods and identify prevention strategies relevant to infection control for hospitals in developing countries. Pandemic influenza preparedness plans must include health care administrative support, mechanisms to rapidly create temporary isolation facilities, systems to restrict access to exposed health care workers, and plans to involve specialists to screen and identify cases early, to provide for continuous monitoring to ensure adherence to optimal infection-control practices, and to provide regular feedback to health care workers


title: Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor

text: Abstract The coronavirus main protease, Mpro, is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential Mpro inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.


title: Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

text: In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.


title: Efficient degradation of chloroquine drug by electro-Fenton oxidation: Effects of operating conditions and degradation mechanism

text: In this work, the degradation of chloroquine (CLQ), an antiviral and antimalarial drug, using electro-Fenton oxidation was investigated. Due to the importance of hydrogen peroxide (H(2)O(2)) generation during electro-Fenton oxidation, effects of pH, current density, molecular oxygen (O(2)) flow rate, and anode material on H(2)O(2) generation were evaluated. H(2)O(2) generation was enhanced by increasing the current density up to 60 mA/cm(2) and the O(2) flow rate up to 80 mL/min at pH 3.0 and using carbon felt cathode and boron-doped diamond (BDD) anode. Electro-Fenton-BDD oxidation achieved the total CLQ depletion and 92% total organic carbon (TOC) removal. Electro-Fenton-BDD oxidation was more effective than electro-Fenton-Pt and anodic oxidation using Pt and BDD anodes. The efficiency of CLQ depletion by electro-Fenton-BDD oxidation raises by increasing the current density and Fe(2+) dose; however it drops with the increase of pH and CLQ concentration. CLQ depletion follows a pseudo-first order kinetics in all the experiments. The identification of CLQ degradation intermediates by chromatography methods confirms the formation of 7-chloro-4-quinolinamine, oxamic, and oxalic acids. Quantitative amounts of chlorides, nitrates, and ammonium ions are released during electro-Fenton oxidation of CLQ. The high efficiency of electro-Fenton oxidation derives from the generation of hydroxyl radicals from the catalytic decomposition of H(2)O(2) by Fe(2+) in solution, and the electrogeneration of hydroxyl and sulfates radicals and other strong oxidants (persulfates) from the oxidation of the electrolyte at the surface BDD anode. Electro-Fenton oxidation has the potential to be an alternative method for treating wastewaters contaminated with CLQ and its derivatives.


title: Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus anthracis Elicit Differential Molecular Expression Patterns

text: Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-γ-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.


In Reply: Challenges in interpreting the diagnostic performance of symptoms to predict COVID‐19 status: the case of anosmia


title: Interferon β-1a for the treatment of Ebola virus disease: A historically controlled, single-arm proof-of-concept trial

text: To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5–1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.


title: Macroprudential Policy and the Probability of Banking Crises()

text: The ultimate purpose of macroprudential policy is to avoid financial instability, such as banking crises, which have a long-lasting and devastating effect on the economy. Although a growing number of studies have examined the effects of macroprudential policy on credit growth, few empirical studies have analyzed its effect on the probability of a banking crisis. Does macroprudential policy actually affect the probability of a banking crisis? Do other macroeconomic policies matter for the effectiveness of macroprudential policy? To answer these questions, this paper empirically investigates the effect of macroprudential policy on the probability of a banking crisis and its relationship with other macroeconomic policies. Specifically, using data on 65 countries from 2000 to 2016, we employ a probit model to analyze the effect of changes in the loan-to-value (LTV) ratio on crisis probability. Our results show that macroprudential policy is effective in changing the probability of a banking crisis via a credit channel and that its effectiveness depends on other macroeconomic policies. Changes in the LTV ratio are found to be effective in influencing the probability of a banking crisis in countries that have inflation targeting frameworks, floating exchange rate regimes, and/or no capital controls. Our results underscore the importance of policy coordination among different government bodies to design an appropriate macroprudential policy, especially in the current context of the Covid-19 crisis.


title: PNEUMONIA | Atypical

text: ‘Atypical pneumonia’ refers to a clinical syndrome associated with pneumonia (typically mild, nonlobar) and diverse upper respiratory tract and extrapulmonary manifestations. Clinical features overlap with bacterial pneumonia, and co-infection with both typical (e.g., Streptococcus pneumoniae or other bacteria) and atypical pathogens may occur. ‘Atypical’ pathogens include Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp. In large epidemiological studies, Mycoplasma pneumoniae has been implicated in 2–18% of community-acquired pneumonias; Chlamydia pneumoniae, in 2–8%; Legionella sp., 1–4%. Atypical pathogens lack cell walls and are resistant to β-lactam antibiotics but are usually susceptible to tetracyclines, macrolides, ketolides, and fluoroquinolone antibiotics. In this article, we also review other unusual causes of pneumonia which are transmitted by insects or vectors (e.g., Rocky Mountain spotted fever, cat scratch fever, Q fever, ehrlichiosis, Lyme disease, and tularemia). These diverse organisms are not found on Gram stain, and diagnosis requires special culture techniques or serological assays. We review the salient clinical and laboratory features of these various disorders, and discuss diagnostic and therapeutic strategies.


title: Clinical retrospective study on the efficacy of Qingfei Paidu decoction combined with Western medicine for COVID-19 treatment

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD) is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P < 0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P < 0.05), and C-reactive protein and creatine kinase were the most pronounced (P < 0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P > 0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.


title: Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China

text: Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6–57 months). The mean maximum temperature (±SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (±SD) for all children was 2.6 ± 1.2 days (range, 1–5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged ⩽6 years each year in Hong Kong.


title: Interactions micro-organismes et voies aériennes distales : spécificités pédiatriques

text: Résumé Le spectre des virus à tropisme respiratoire s’élargit et des maladies émergentes sont régulièrement décrites depuis une quinzaine d’années. L’origine de ces virus respiratoires émergents peut être zoonotique (par franchissement de barrière d’espèce, après mutations pour les virus à ARN tels que les virus aviaires influenza de type A ou les coronavirus), ou liée aux nouvelles techniques d’identification (métapneumovirus, bocavirus). Les relations entre bronchiolite et asthme sont désormais mieux appréhendées grâce au suivi prospectif de cohortes de nouveau-nés. Le rôle des rhinovirus devient prépondérant par rapport au virus respiratoire syncytial. L’identification de facteurs de prédispositions immunologiques, fonctionnelles, atopiques et génétiques, pour la survenue de l’asthme après une infection à rhinovirus suggère que l’infection virale révèle un terrain prédisposé plutôt qu’elle est à l’origine de l’asthme. Le rôle des bactéries dans l’histoire naturelle de l’asthme commence également à être mieux cerné. Les résultats de la cohorte danoise COPSAC ont montré la fréquence des identifications bactériennes au cours des épisodes sifflants avant 3 ans, ainsi que l’impact de la colonisation bactérienne à l’âge de un mois sur la survenue de l’asthme à l’âge de 5 ans. Le rôle des infections bactériennes dans l’asthme sévère du jeune enfant est également discuté. Summary The spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. The origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to RNA viruses such as avian influenza virus type A or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). The relationship between bronchiolitis and asthma is now better understood thanks to prospective follow up of birth cohorts. The role of rhinovirus has become predominant with respect to respiratory syncytial virus. The identification of predisposing factors immunological, functional, atopic and genetic, for the onset of asthma after rhinovirus infection suggests that viral infection reveals a predisposition rather than itself being a cause of asthma. The role of bacteria in the natural history of asthma is also beginning to be better understood. The results of the COPSAC Danish cohort have shown the frequency of bacterial identification during wheezy episodes before 3 years, and the impact of bacterial colonization at the age of one month on the onset of asthma by age 5 years. The role of bacterial infections in severe asthma in young children is also discussed.


title: Diagnóstico microbiológico de las infecciones del tracto respiratorio superior

text: Las infecciones del tracto respiratorio superior se hallan entre las más frecuentes, y generan más consultas médicas que cualquier otro tipo de enfermedad infecciosa. Se incluyen los procedimientos de diagnóstico de los siguientes síndromes: faringitis estreptocócica y no estreptocócica, síndromes laríngeos, otitis, sinusitis y otras infecciones causadas por hongos y bacterias raros y/o poco frecuentes: síndrome de Lemierre, angina de Vincent, abscesos faríngeos y periamigdalares, difteria, candidiasis y zigomicosis. Se incluye información detallada sobre la recogida y procesamiento de las muestras, elección de pruebas de laboratorio, criterios de interpretación, información de resultados, procedimientos adicionales en infecciones poco frecuentes, y la utilidad de nuevas técnicas. Toda la información incluida en este artículo está contenida en los Procedimientos de Microbiología Clínica (http://www.seimc.org/protocolos/microbiologia/) Upper respiratory tract (URT) infections are common and account for more medical visits than any other type of infectious disease. Diagnostic procedures for the following syndromes are included in this report: Streptococcal and nonstreptococcal pharyngitis, laryngeal syndromes, otitis, sinusitis, and others caused by unusual and/or uncommon bacteria or fungi, including Lemierre's disease, Vincent's angina, pharyngeal and peritonsillar abscesses, diphtheria, candidiasis, and zygomycoses. Detailed information is provided on specimen collection and processing, selection of laboratory tests, interpretation of findings, reporting results, additional procedures for uncommon infections, and the use of new techniques. All the information included in this article is contained in the Standard Operating Procedures for Clinical Microbiology (http://www.seimc.org/protocolos/microbiologia/).


title: Seasonality, ambient temperatures and hospitalizations for acute exacerbation of COPD: a population-based study in a metropolitan area

text: BACKGROUND: Excluding the tropics, exacerbations of chronic obstructive pulmonary disease (COPD) are more frequent in winter. However, studies that directly relate hospitalizations for exacerbation of COPD to ambient temperature are lacking. The aim of this study was to assess the influence of temperature on the number of hospitalizations for COPD. METHODS: This was a population-based study in a metropolitan area. All hospital discharges for acute exacerbation of COPD during 2009 in Barcelona and its metropolitan area were analyzed. The relationship between the number of hospitalizations for COPD and the mean, minimum, and maximum temperatures alongside comorbidity, humidity, influenza rate, and environmental pollution were studied. RESULTS: A total of 9,804 hospitalization discharges coded with COPD exacerbation as a primary diagnosis were included; 75.4% of cases were male with a mean age of 74.9±10.5 years and an average length of stay of 6.5±6.1 days. The highest number of admissions (3,644 [37.2%]) occurred during winter, followed by autumn with 2,367 (24.1%), spring with 2,347 (23.9%), and summer with 1,446 (14.7%; P<0.001). The maximum, minimum, and mean temperatures were associated similarly with the number of hospitalizations. On average, we found that for each degree Celsius decrease in mean weekly temperature, hospital admissions increased by 5.04% (r(2)=0.591; P<0.001). After adjustment for humidity, comorbidity, air pollution, and influenza-like illness, only mean temperatures retained statistical significance, with a mean increase of 4.7% in weekly admissions for each degree Celsius of temperature (r(2)=0.599, P<0.001). CONCLUSION: Mean temperatures are closely and independently related to the number of hospitalizations for COPD.


title: Coronaviruses in Avian Species – Review with Focus on Epidemiology and Diagnosis in Wild Birds

text: Coronaviruses (CoVs) are a large group of enveloped viruses with a single-strand RNA genome, which continuously circulate in mammals and birds and pose a threat to livestock, companion animals, and humans. CoVs harboured by avian species are classified to the genera gamma- and deltacoronaviruses. Within the gamma-CoVs the main representative is avian coronavirus, a taxonomic name which includes the highly contagious infectious bronchitis viruses (IBVs) in chickens and similar viruses infecting other domestic birds such as turkeys, guinea fowls, or quails. Additionally, IBVs have been detected in healthy wild birds, demonstrating that they may act as the vector between domestic and free-living birds. Moreover, CoVs other than IBVs, are identified in wild birds, which suggests that wild birds play a key role in the epidemiology of other gammaCoVs and deltaCoVs. Development of molecular techniques has significantly improved knowledge of the prevalence of CoVs in avian species. The methods adopted in monitoring studies of CoVs in different avian species are mainly based on detection of conservative regions within the viral replicase, nucleocapsid genes, and 3’UTR or 5’UTR. The purpose of this review is to summarise recent discoveries in the areas of epidemiology and diagnosis of CoVs in avian species and to understand the role of wild birds in the virus distribution.


title: Human FcR Polymorphism and Disease

text: Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture.


title: Considerations for Safety in the Use of Systemic Medications for Psoriasis and Atopic Dermatitis during the COVID‐19 pandemic

text: Coronavirus disease 2019 (COVID‐19), is responsible for at least 2,546,527 cases and 175,812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased to COVID‐19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of non‐biologic and biologic systemic medications for psoriasis and atopic dermatitis, and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the JAK inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)‐17, IL‐12/23 and IL‐23 inhibitors are associated with low infection risk, with IL‐17 and IL‐23 favored over IL‐12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL‐17 and IL‐23 blockers are safer than TNF‐blockers. Apremilast, acitretin and dupilumab, have favorable safety data, and may be safely initiated and continued in uninfected patients. Without definitive COVID‐19 data, these recommendations may be useful in guiding treatment of psoriasis and atopic dermatitis patients during the COVID‐19 pandemic. This article is protected by copyright. All rights reserved.


title: 12 Wine, Food and Health

text: Wine has historically been associated with religious rights, used as a salubrious beverage, employed as a medication as well as a medicinal solvent, and consumed as a food accompaniment. It is the latter that is most intimately associated in the minds of most modern consumers. Despite this, there is little flavor commonality on which pairing could be based. The first section of the chapter examines this feature, and wine’s primary role as a palate cleanser and food condiment. The synergistic role of food and wine in suppressing each other’s least pleasant attributes is also explained. The final section deals with the latest evidence relating to the many beneficial health effects of moderate wine consumption, shortfalls in the data, headache induction, dental erosion, and conditions under which wine intake is contraindicated.


title: Management of clozapine treatment during the COVID-19 pandemic

text: Clozapine is the only available treatment for refractory schizophrenia but its use involves frequent physical contact with healthcare workers for the purpose of mandatory blood monitoring. During the COVID-19 pandemic, patients taking clozapine will be self-isolating to reduce the risk of infection, not least because these patients are at high risk of serious illness and fatality because of high rates of diabetes, obesity and pulmonary disease and an increased risk of pneumonia. Problems may also arise because both clozapine-induced myocarditis and neutropenic sepsis share signs and symptoms with COVID-19 (fever, chest pain, dyspnoea, etc.). We recommend decreasing the frequency of physical contacts by extending the blood monitoring interval to 12 weeks in those patients taking clozapine for more than 1 year. To distinguish COVID-19 from clozapine-related physical adverse effects, we suggest an urgent antigen test alongside a full blood count. In those taking clozapine who develop COVID-19, we suggest continuing with clozapine whenever possible (even during ventilation), reducing the dose if necessary in line with blood assay results. Blood monitoring should continue but clozapine should only cease if there is a significant fall in neutrophils (COVID-19 is linked to lymphopenia but not neutropenia). To protect against the likelihood and severity of respiratory infection, we recommend the use of vitamin D in all clozapine patients. Initiation of clozapine is likely to remain problematic while the risk of infection remains, given the degree of physical contact required to assure safety.


docid: wdrrpfds

title: Colorectal cancer services during the COVID‐19 pandemic


Carbon footprint of air travel to international radiology conferences: FOMO?


title: A Protocol for Wide Awake Local Anaesthetic No Tourniquet (WALANT) hand surgery in the context of the Coronavirus disease 2019 (COVID-19) pandemic

text: Abstract There are new and unique challenges to emergency surgery service provision posed by the Coronavirus disease 2019 global pandemic. It is in the best interests of patients for care providers to streamline services where possible to maximise the number of cases that can be performed by limited surgical and anaesthetic teams, as well as minimising patient interactions and admission times to reduce potential spread of the virus. There is evidence that wide awake local anaesthetic no tourniquet (WALANT) hand and upper limb surgery can meet this need in a number of ways, including reduced pre-operative work up, the lack of a need for an anaesthetist or ventilator, shorter inpatient stays and improved cost efficiencies. Though updated national guidelines exist that advocate increased use of WALANT surgery in response to the pandemic there are not yet clear protocols to facilitate this. We outline a protocol being developed at one UK Major Trauma Centre tailored to the expansion of WALANT hand and upper limb emergency surgery with particular emphasis on facilitating timely surgical care while minimising healthcare encounters pre and post-operatively. This will serve to reduce potential transmission of the virus and create cost efficiencies to free funding for COVID-19 related care. Our protocol is easily replicable and may be of benefit to other centres dealing with emergency upper limb surgery in the new climate of COVID-19.


title: Viral proteomics: The emerging cutting-edge of virus research

text: Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment. They encode a wide spectrum of multifunctional proteins, which interplay with and modify proteins in host cells. Viral genomes were chronologically the first to be sequenced. However, the corresponding viral proteomes, the alterations of host proteomes upon viral infection, and the dynamic nature of proteins, such as post-translational modifications, enzymatic cleavage, and activation or destruction by proteolysis, remain largely unknown. Emerging high-throughput techniques, in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes, have been applied to define viruses and their interactions with their hosts. Here, we review the major areas of viral proteomics, including virion proteomics, structural proteomics, viral protein interactomics, and changes to the host cell proteome upon viral infection.


title: cAMP-dependent activation of protein kinase A attenuates respiratory syncytial virus-induced human airway epithelial barrier disruption

text: Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs. Structure and functions of the Apical Junctional Complex (AJC) were evaluated by measuring transepithelial electrical resistance and permeability to FITC-dextran, and determining localization of AJC proteins by confocal microscopy. Increased intracellular cAMP level significantly attenuated RSV-induced disassembly of AJC. These barrier-protective effects of cAMP were due to the activation of PKA signaling and did not involve Epac activity. Increased cAMP level reduced RSV-induced reorganization of the actin cytoskeleton, including apical accumulation of an essential actin-binding protein, cortactin, and inhibited expression of the RSV F protein. These barrier-protective and antiviral-function of cAMP signaling were evident even when cAMP level was increased after the onset of RSV infection. Taken together, our study demonstrates that cAMP/PKA signaling attenuated RSV-induced disruption of structure and functions of the model airway epithelial barrier by mechanisms involving the stabilization of epithelial junctions and inhibition of viral biogenesis. Improving our understanding of the mechanisms involved in RSV-induced epithelial dysfunction and viral pathogenesis will help to develop novel anti-viral therapeutic approaches.


title: The use of cells from ANPEP knockout pigs to evaluate the role of aminopeptidase N (APN) as a receptor for porcine deltacoronavirus (PDCoV)

text: Abstract The coronaviruses, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine deltacoronavirus (PDCoV) represent important sources of neonatal diarrhea on pig farms. The requirement for aminopeptidase N (APN) as a receptor for TGEV, but not for PEDV, is well established. In this study, the biological relevance of APN as a receptor for PDCoV was tested by using CRISPR/Cas9 to knockout the APN gene, ANPEP, in pigs. Porcine alveolar macrophages (PAMs) from ANPEP knockout (KO) pigs showed resistance to PDCoV infection. However, lung fibroblast-like cells, derived from the ANPEP KO PAM cultures, supported PDCoV infection to high levels. The results suggest that APN is a receptor for PDCoV in PAMs but is not necessary for infection of lung-derived fibroblast cells. The infection of the ANPEP KO pigs with PDCoV further confirmed that APN is dispensable as a receptor for PDCoV.


title: Coronavirus disease-2019: is fever an adequate screening for the returning travelers?

text: On Thursday, 30 January 2020, World Health Organization declared Coronavirus disease-2019 (COVID-2019) a Public Health Emergency of International Concern. Since its identification in late December 2019 in Wuhan, Hubei Province, People’s Republic of China, the number of cases imported into other countries is increasing, and the epidemiological map is changing rapidly. On the other hand, body temperature screening (fever) is the major test performed at points of entry, i.e., airports, in the returning travelers in most of the countries with limited resources. However, the recent report on asymptomatic contact transmission of COVID-19 and travelers who passed the symptoms-based screening and tested positive for COVID-19 using reverse transcription polymerase chain reaction (RT-PCR) challenges this approach as body temperature screening may miss travelers incubating the disease or travelers concealing fever during travel. On this note, travel restrictions to and from high risk areas and/or 14 days quarantine of travelers coming from high risk areas are recommended to prevent possible importation of COVID-19. Currently, RT-PCR is a reliable test in detecting both symptomatic and asymptomatic COVID-19.


title: Attributable Risk to Assess the Health Impact of Air Pollution: Advances, Controversies, State of the Art and Future Needs

text: Despite the increased attention given to the health impact assessment of air pollution and to the strategies to control it in both scientific literature and concrete interventions, the results of the implementations, especially those involving traffic, have not always been satisfactory and there is still disagreement about the most appropriate interventions and the methods to assess their effectiveness. This state-of-the-art article reviews the recent interpretation of the concepts that concern the impact assessment, and compares old and new measurements of attributable risk and attributable fraction. It also summarizes the ongoing discussion about the designs and methods for assessing the air pollution impact with particular attention to improvements due to spatio-temporal analysis and other new approaches, such as studying short term effects in cohorts, and the still discussed methods of predicting the values of attributable risk (AR). Finally, the study presents the more recent analytic perspectives and the methods for directly assessing the effects of not yet implemented interventions on air quality and health, in accordance with the suggestion in the strategic plan 2020−2025 from the Health Effect Institute.


docid: vasphfdy

title: Use of ribavirin in viruses other than hepatitis C. A review of the evidence

text: Abstract Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.


Activation of Ang-(1-7)/Mas Receptor Is a Possible Strategy to Treat Coronavirus (SARS-CoV-2) Infection


title: Self-reported anticipated compliance with physician advice to stay home during pandemic (H1N1) 2009: Results from the 2009 Queensland Social Survey

text: BACKGROUND: One strategy available to public health officials during a pandemic is physician recommendations for isolation of infected individuals. This study was undertaken during the height of the Australian pandemic (H1N1) 2009 outbreak to measure self-reported willingness to comply with physician recommendations to stay home for seven days, and to compare responses for the current strain of pandemic influenza, avian influenza, seasonal influenza, and the common cold. METHODS: Data were collected as part of the Queensland Social Survey (QSS) 2009, which consisted of a standardized introduction, 37 demographic questions, and research questions incorporated through a cost-sharing arrangement. Four questions related to respondents' anticipated compliance with a physician's advice to stay home if they had a common cold, seasonal influenza, pandemic (H1N1) 2009 influenza or avian influenza were incorporated into QSS 2009, with responses recorded using a balanced Likert scale ranging from "very unlikely" to "very likely." Discordance between responses for different diseases was analysed using McNemar's test. Associations between demographic variables and anticipated compliance were analysed using Pearson's chi-square or chi-square for linear-by-linear association, and confirmed using multivariate logistic regression; p < 0.05 was used to establish statistical significance. RESULTS: Self-reported anticipated compliance increased from 59.9% for the common cold to 71.3% for seasonal influenza (p < .001), and to 95.0% for pandemic (H1N1) 2009 influenza and 94.7% for avian influenza (p < 0.001 for both versus seasonal influenza). Anticipated compliance did not differ for pandemic (H1N1) 2009 and avian influenza (p = 0.815). Age and sex were both associated with anticipated compliance in the setting of seasonal influenza and the common cold. Notably, 27.1% of health and community service workers would not comply with physician advice to stay home for seasonal influenza. CONCLUSIONS: Ninety-five percent of people report they would comply with a physicians' advice to stay home for seven days if they are diagnosed with pandemic (H1N1) 2009 or avian influenza, but only 71% can be expected to comply in the setting of seasonal influenza and fewer still can be expected to comply if they are diagnosed with a common cold. Sub-populations that might be worthwhile targets for public health messages aimed at increasing the rate of self-imposed isolation for seasonal influenza include males, younger people, and healthcare workers.


title: Fluorescent, colourimetric, and ratiometric probes based on diverse fluorophore motifs for mercuric(II) ion (Hg(2+)) sensing: highlights from 2011 to 2019

text: Though it has not been shown to deliver any biological importance, mercuric(II) ion (Hg(2+)) is a deleterious cation which poses grievous effects to the human body and/or the ecosystem, hence, the need for its sensitive and selective monitoring in both environmental and biological systems. Over the years, there has been a great deal of work in the use of fluorescent, colourimetric, and/or ratiometric probes for Hg(2+) recognition. Essentially, the purpose of this review article is to give an overview of the advances made in the constructions of such probes based on the works reported in the period from 2011 to 2019. Discussion in this review work has been tailored to the kinds of fluorophore scaffolds used for the constructions of the probes reported. Selected examples of probes under each fluorophore subcategory were discussed with mentions of the typically determined parameters in an analytical sensing operation, including modulation in fluorescence intensity, optimal pH, detection limit, and association constant. The environmental and biological application ends of the probes were also touched where necessary. Important generalisations and conclusions were given at the end of the review. This review article highlights 196 references.


title: Temporal changes in psychobehavioral responses during the 2009 H1N1 influenza pandemic

text: Abstract Objectives This paper aimed to examine the temporal changes in psychobehavioral responses in relation to reported 2009 H1N1 influenza deaths. Methods Telephone interviews with 1050 members of the lay public in the Kuala Lumpur metropolitan area, Malaysia, were conducted between July 11 and September 12, 2009. Results The study demonstrated that public psychobehavioral responses closely mirrored the daily number of reported deaths due to 2009 H1N1 influenza. During the weeks of escalating reported deaths, sharp rises of various domains of fear, health avoidance and protective behaviors, and impact were observed. In particular, health avoidance and protective behaviors decreases were consistent with the decline of reported deaths, indicating the paramount importance of efforts to sustain behavioral change in the general public. Conclusions These temporal trends provide important guidance toward health promotion and prevention initiatives in future outbreaks.


title: Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson’s disease induced by the Japanese encephalitis virus

text: A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor, significantly increased norepinephrine and 5-hydroxytryptamine concentrations in the rat brain and also significantly increased acetylcholine and dopamine (DA) levels in the rat striatum. Urinary isatin concentrations in patients with Parkinson’s disease tend to increase according to the severity of disease. We have developed a rat model of Parkinson’s disease induced by the Japanese encephalitis virus (JEV). The distribution of the pathological lesions of JEV-rats resemble those found in Parkinson’s disease. Significant behavioral improvement was observed in JEV-rats after isatin, L-DOPA and selegiline administration using a pole test. Both isatin and selegiline prevented the decrease in striatum DA levels of JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not selegiline. These findings suggest that JEV-infected rats may serve as a model of Parkinson’s disease and that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.


docid: shisdsyk

title: Closing in on the causes of host shutoff

text: Influenza A virus suppresses the translation of host mRNA by selectively remodeling and dominating the pool of mRNA in infected cells.


title: Acral purpuric lesions (Erythema multiforme type) associated with thrombotic vasculopathy in a child during the COVID‐19 pandemic

text: Since the beginning of the COVID‐19 pandemic, different types of cutaneous manifestations have been reported. In Spain, there were reports in the first weeks of April 2020 of an increase in purpuric acral lesions similar to perniosis on the hands and especially the feet of children and young adults. These patients do not normally present with clinical manifestations linked to COVID‐19, and their PCR and serological tests are usually negative for specific IgM and IgG.


title: The pulmonary sequalae in discharged patients with COVID-19: a short-term observational study

text: BACKGROUND: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia were discharged from hospitals in Wuhan, China. We aimed to determine the cumulative percentage of complete radiological resolution at each time point, to explore the relevant affecting factors, and to describe the chest CT findings at different time points after hospital discharge. METHODS: Patients with COVID-19 pneumonia confirmed by RT-PCR who were discharged consecutively from the hospital between 5 February 2020 and 10 March 2020 and who underwent serial chest CT scans on schedule were enrolled. The radiological characteristics of all patients were collected and analysed. The total CT score was the sum of non-GGO involvement determined at discharge. Afterwards, all patients underwent chest CT scans during the 1st, 2nd, and 3rd weeks after discharge. Imaging features and distributions were analysed across different time points. RESULTS: A total of 149 patients who completed all CT scans were evaluated; there were 67 (45.0%) men and 82 (55.0%) women, with a median age of 43 years old (IQR 36–56). The cumulative percentage of complete radiological resolution was 8.1% (12 patients), 41.6% (62), 50.3% (75), and 53.0% (79) at discharge and during the 1st, 2nd, and 3rd weeks after discharge, respectively. Patients ≤44 years old showed a significantly higher cumulative percentage of complete radiological resolution than patients > 44 years old at the 3-week follow-up. The predominant patterns of abnormalities observed at discharge were ground-glass opacity (GGO) (125 [83.9%]), fibrous stripe (81 [54.4%]), and thickening of the adjacent pleura (33 [22.1%]). The positive count of GGO, fibrous stripe and thickening of the adjacent pleura gradually decreased, while GGO and fibrous stripe showed obvious resolution during the first week and the third week after discharge, respectively. “Tinted” sign and bronchovascular bundle distortion as two special features were discovered during the evolution. CONCLUSION: Lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term follow-up with no sequelae. Two weeks after discharge might be the optimal time point for early radiological estimation.


title: Dilated Cardiomyopathy in Juvenile Portuguese Water Dogs

text: Dilated cardiomyopathy recently has been recognized in juvenile Portuguese Water Dogs. The purpose of this study was to evaluate unaffected and affected puppies by physical examination, electrocardiogram (ECG), echocardiogram, specific biochemical assays, and ultrastructure to document disease progression and to develop a method of early detection. Results of segregation analysis were consistent with autosomal recessive inheritance. Of 124 puppies evaluated clinically and echocardiographically, 10 were affected. No significant differences were found between unaffected and affected puppies for blood and myocardial carnitine or taurine concentrations, serum chemical variables, results of ophthalmological examinations, ECGs, or measurement of urine metabolites. Ultrastructural examination of myocardium from affected dogs revealed myofibrillar atrophy and small regions of myo‐fibrillar degeneration, most prominently at the region of the intercalated discs. Only echocardiography allowed detection of affected puppies before clinical signs became evident. Echocardiography revealed a significant difference in the shortening fraction, E point to septal separation, and the end systolic and diastolic left ventricular internal diameters. Affected puppies were detected 1–4 weeks before the development of acute congestive heart failure.


title: Diarrhées infectieuses d'importation : diagnostic étiologique

text: Résumé Les diarrhées infectieuses d'importation sont très bien connues des voyageurs puisque c'est la pathologie la plus fréquente au retour d'un pays tropical [41]. La contamination oro-fécale est le principal mode de transmission. Les agents responsables sont le plus souvent d'origine bactérienne (Escherichia coli entérotoxinogènes (40 %), salmonelles (15 %) par exemple), alors que les virus et les parasites ne représentent que 15 à 20 % des étiologies. Une revue de la littérature retrace les mécanismes physiopathologiques, les manifestations cliniques et les techniques biologiques les plus courantes pour aboutir au diagnostic étiologique. Abstract Traveler's diarrhea is the most frequent illness while traveling in tropical countries. It is usually acquired through ingestion of fecally contaminated food or water. Etiological agents are mainly bacteria : enterotoxic Escherichia coli (40 %), Shigella (15 %), whereas viruses and parasites are only responsible for 15 to 20 % of traveler's diarrhea. This litterature review reports the physiopathological mecanisms, the major epidemiological events and the most usual laboratory techniques to reach the diagnosis.


Biosecurity and Dual-Use Research: Gaining Function – But at What Cost?


title: An interferon‐γ‐related cytokine storm in SARS patients

text: Fourteen cytokines or chemokines were analyzed on 88 RT‐PCR‐confirmed severe acute respiratory syndrome (SARS) patients. IFN‐γ, IL‐18, TGF‐β, IL‐6, IP‐10, MCP‐1, MIG, and IL‐8, but not of TNF‐α, IL‐2, IL‐4, IL‐10, IL‐13, or TNFRI, were highly elevated in the acute phase sera of Taiwan SARS patients. IFN‐γ was significantly higher in the Ab(+) group than in the Ab(−) group. IFN‐γ, IL‐18, MCP‐1, MIG, and IP‐10 were already elevated at early days post fever onset. Furthermore, levels of IL‐18, IP‐10, MIG, and MCP‐1 were significantly higher in the death group than in the survival group. For the survival group, IFN‐γ and MCP‐1 were inversely associated with circulating lymphocytes count and monocytes count, but positively associated with circulating neutrophils count. It is concluded that an interferon‐γ‐related cytokine storm was induced post SARS coronavirus infection, and this cytokine storm might be involved in the immunopathological damage in SARS patients. J. Med. Virol. 75:185–194, 2005. © 2004 Wiley‐Liss, Inc.


Hallazgos ecocardiográficos en pacientes críticos por COVID-19


title: Asthma in children: mapping the literature by bibliometric analysis

text: Abstract Aim. – To evaluate the publication output associated with research on asthma in children. Methods. – The data encompassed the period from 1991 to 2002 and were extracted from the Science Citation Index online version. Selected documents included ‘asthmatic children’ and ‘asthma children’ as a part of its title, abstract, or keyword from. Parameters analyzed included language, type of document, page count, publication output, country of publication, authorship, publication pattern, and the most frequently cited paper. Results. – The yearly publications have increased from 1991 to 2002. The seven industrialized countries have high productivity in this research field. English was the dominant language, and four or five authors were the moot common number of co-author. The US was the world leader and dominated most of the publications, followed by the UK. Conclusions. – The most important functions of scientific publications are to communicate and exchange research findings and results. The results of the study not only offer a comprehensive picture of asthma in children by bibliometric research, but also demonstrate the performance of research workers, institutions, and even countries.


title: Surgery during the COVID‐19 pandemic: operating room suggestions from an international Delphi process

text: INTRODUCTION: Operating room (OR) practice during the COVID‐19 pandemic is driven by basic principles, shared experience, and nascent literature. This study aimed to identify the knowledge needs of the global OR workforce, and characterise supportive evidence to establish consensus. METHODS: A rapid, modified Delphi exercise was performed, open to all stakeholders, informed via an online international collaborative evaluation. RESULTS: The consensus exercise was completed by 339 individuals from 41 countries (64% UK). Consensus was reached on 71/100 statements, predominantly standardisation of OR pathways, OR staffing, and pre‐operative screening or diagnosis. The highest levels of consensus were observed in statements relating to appropriate personal and protective equipment (PPE) and risk distribution (96‐99%), clear consent processes (96%), multidisciplinary decision‐making and working (97%). Statements yielding equivocal responses predominantly related to technical and procedure choices, including: decontamination (40‐68%), laminar flow systems (13‐61%), PPE reuse (58%), risk stratification of patients (21‐48%), open vs. laparoscopic surgery (63%), preferential cholecystostomy in biliary disease (48%), and definition of aerosol generating procedures (19%). DISCUSSION: High levels of consensus existed for many statements within each domain, supporting much of the initial guidance issued by professional bodies, yet several contentious areas arose, which represent urgent targets for investigation to delineate safe COVID‐19 related OR practice. This article is protected by copyright. All rights reserved.


docid: lwchtzmr

title: BARIATRIC AND METABOLIC SURGERY DURING COVID-19 OUTBREAK PHASE-2 IN ITALY: WHY, WHEN AND HOW TO RESTART


title: Analysis of the Korean Emergency Department Syndromic Surveillance System: Mass Type Acute Diarrheal Syndrome

text: OBJECTIVES: This study was designed to compare the data from the emergency department syndromic surveillance system of Korea in detection and reporting of acute diarrheal syndrome (mass type) with the data from the Korea Food and Drug Administration. And to offer fundamental materials for making improvements in current surveillance system was our purpose. METHODS: A study was conducted by reviewing the number of cases reported as acute diarrheal syndrome (mass type) from the Korean Center for Disease Control and Prevention between June, 2002 and July, 2008. And the data were compared with the number of mass food poisoning cases during the same period, reported from the Korea Food and Drug Administration. The difference between two groups was measured and their transitions were compared. RESULTS: The emergency department syndromic surveillance system's reports of the numbers of acute diarrheal syndrome (mass type) cases were different from the transition of mass food poisonings, reported by the Korea Food and Drug Administration. Their reports were not accurate and they could not follow the trends of increase in mass food poisonings since 2002. CONCLUSIONS: Current problems in the emergency department syndromic surveillance system in Korea are mostly related to inaccuracies of daily data reporting system. Manual data input by the reporters could play a big role in such inaccuracies. There need to be improvements in the ways of reporting data, such as automated information transport system linking electronic medical record.


title: Intranasal Administration of dsRNA Analog Poly(I:C) Induces Interferon-α Receptor-Dependent Accumulation of Antigen Experienced T Cells in the Airways

text: Polyriboinosinic-polyribocytoidylic acid (pIC), a synthetic dsRNA, acts as an adjuvant that boosts immune responses and protection. Intranasal (IN) administration of pIC has recently been used to adjuvant influenza virus vaccines; however, the effects of IN pIC administration on pulmonary T cell responses remain unclear. Here we show that a single IN administered dose of dsRNA into mice induced local Th1 chemokine production in the lungs and airways, and generated a biphasic and sustained migration of T lymphocytes to the airways. Furthermore, IN pIC-induced chemokine production and T cell recruitment to the airways were interferon-α receptor (IFNAR) signaling dependent. The effect of dsRNA on T cell recruitment to the airways was also dependent on the presence of high molecular weight (HMW) pIC, as a low molecular weight (LMW) pIC preparation known to only interact with TLR3 did not elicit the same effect on T cell migration to the airways, suggesting that the observed effects were dependent upon dsRNA recognition by multiple pattern recognition receptors (PPRs). IN pIC was additionally capable of stimulating low levels of T cell proliferation in the draining lymph nodes approximately 4–6 days after treatment that preceded a small population of de-novo T cells found in the airways by day 10. Taken together, these results demonstrate that the adjuvant effect of IN pIC that results in enhanced T cell proliferation and sustained T cell recruitment to the airways requires multiple PRRs and IFNAR signaling.


Preparing for the COVID-19 Pandemic Our Experience in New York


title: Why be a vegetarian?

text: Unknown


title: Rehabilitación En Época De Confinamiento

text: Abstract The health system is facing a global pandemic due to coronavirus disease 2019 (COVID-19). Emergency plans often fail to consider specific rehabilitation issues, whether inpatient or outpatient, although the World Health Organisation advises the inclusion of rehabilitation professionals as soon as possible. The contingency plans of rehabilitation services must be carried out in coordination with the other healthcare areas. This review was prepared with the current available evidence on COVID-19 and was based on the experience of a specific environment, to plan the continuity of rehabilitation care for all patients and to help rehabilitation teams in this period of lockdown and uncertain lifting of restrictions.


title: Rural and Remote Cardiology During the COVID-19 Pandemic: Cardiac Society of Australia and New Zealand (CSANZ) Consensus Statement #

text: Abstract The Challenges Rural and remote Australians and New Zealanders have a higher rate of adverse outcomes due to acute myocardial infarction (AMI), driven by many factors. The prevalence of cardiovascular disease (CVD) is also higher in regional and remote populations, and people with known CVD have increased morbidity and mortality from coronavirus disease 2019 (COVID-19). In addition, COVID-19 is associated with serious cardiac manifestations, potentially placing additional demand on limited regional services at a time of diminished visiting metropolitan support with restricted travel. Inter-hospital transfer is currently challenging as receiving centres enact pandemic protocols, creating potential delays, and cardiovascular resources are diverted to increasing intensive care unit (ICU) and emergency department (ED) capacity. Regional and rural centres have limited staff resources, placing cardiac services at risk in the event of staff infection or quarantine during the pandemic. Main recommendations Health districts, cardiologists and government agencies need to minimise impacts on the already vulnerable cardiovascular health of regional and remote Australians and New Zealanders throughout the COVID-19 pandemic. Changes in management should include: • Improved access to telehealth consultation for regional and rural outpatients. Specialist-led 24/7 ECG reading and acute cardiology services, uniformly covering all rural inpatients, to minimise potential impacts on acute care. • Transfer models incorporating discussion between clinicians and ambulance, balancing urgency with considerations of ambulance capacity in rural locations. • Protection of the role of specialist cardiovascular nurses, avoiding COVID-19 redeployment to maintain rural cardiac service capacity. • An urgent shift to regional models for pacing services, utilising remote monitoring supported by local device implantation and local technicians..


docid: ljsblrur

title: Antibiotic Use and Respiratory Pathogens in Adults With Sickle Cell Disease and Acute Chest Syndrome

text: Background: Acute chest syndrome (ACS) is an acute complication of sickle cell disease (SCD). Historically, the most common pathogens were Chlamydophila pneumoniae, Mycoplasma pneumoniae, and respiratory syncytial virus. Pediatric patients receiving guideline-adherent therapy experienced fewer ACS-related and all-cause 30-day readmissions compared with those receiving nonadherent therapy. This has not been evaluated in adults. Objectives: The primary objectives were to characterize antibiotic use and pathogens. The secondary objective was to assess the occurrence of readmissions associated with guideline-adherent and clinically appropriate treatment compared with regimens that did not meet those criteria. Methods: A retrospective cohort analysis was conducted for adults with SCD hospitalized between August 1, 2014, and July 31, 2017, with pneumonia (PNA) or ACS. The study was approved by the institutional review board. Results: A total of 139 patients with 255 hospitalizations were reviewed. Among 41 respiratory cultures, 3 organisms were isolated: Cryptococcus neoformans, Pseudomonas aeruginosa, and budding yeast. Respiratory panels were collected on 121 admissions, with 17 positive for 1 virus; all were negative for Chlamydophila pneumoniae and M pneumoniae. There were significantly more ACS-/PNA-related 7-day readmissions from patients on guideline-adherent regimens compared with nonadherent regimens (3.7% vs 0%; P = 0.04). Conclusion and Relevance: These findings challenge existing knowledge regarding the most common pathogens in adults with SCD with ACS or PNA. Routine inclusion of a macrolide may not be necessary. Future studies focused on pathogen characterization with standardized assessment are necessary to determine appropriate empirical therapy in this population.


title: COVID‐19 and paediatric health services: A survey of paediatric physicians in Australia and New Zealand

text: AIMS: COVID‐19 is now a global pandemic. At the time of survey, fewer than 150 children in Australia and New Zealand had documented infection. The aim of this study was to assess attitudes, readiness and confidence in the early stages of the COVID‐19 pandemic through an online survey of paediatric physicians and sub‐specialists across Australia and New Zealand. METHODS: Multiple email list groups were used to contact paediatric physicians to undertake an online Likert scale survey between 17 and 24 March. Respondents' specialty, experience and work setting were recorded. Ordinal logistic regression was used to determine respondent factors. RESULTS: There were 542 respondents from across Australia and New Zealand: an estimated 11% of the paediatric physician workforce. A minority (36.6%) agreed that their national response had been well coordinated; the majority (92.7%) agreed that senior‐level hospital administrators were taking the situation seriously. Most reported a good understanding of the natural history of COVID‐19 in children, and knowledge of where to find local information. A large proportion of physicians (86.1%) were worried about becoming infected through their work; few (5.8%) reported that they would not come to work to avoid infection. Closure of school and childcares would reduce the ability to continue work at current capacity for 23.6% of respondents. CONCLUSION: Despite limited experience in pandemics, most paediatric physicians felt informed. Concern about exposure at work is common; most were willing to work regardless. The closure of schools and daycares may have an impact on staffing. Coordination and leadership will be critical.


title: A virologic survey of patients admitted to a critical care unit for acute cardiorespiratory failure

text: OBJECTIVE: To document the prevalence of respiratory virus infections in patients with chronic cardiac or pulmonary disorders admitted to a critical care unit for acute cardiorespiratory failure. DESIGN, SETTING, PATIENTS: The study took place in a critical care unit during two consecutive winters. All patients admitted to the unit for acute respiratory or cardiac failure were enrolled. A nasal swab was taken for polymerase chain reaction (PCR) detection of influenza virus, respiratory syncytial virus (RSV), metapneumovirus, rhinovirus, and coronavirus. RESULTS: One hundred twenty-two patients were enrolled. Their mean age was 69 years; 42% of the patients were female; the new simplified acute physiology score (SAPS II) score on admission was 35.6; 94% of patients had acute respiratory failure, 14% reported “influenza-like” illness before admission, and 11% of patients died in the unit. Twenty-one patients (17%) tested positive for a respiratory virus. The per-1,000 positivity rates were influenza virus 66, RSV 49, rhinovirus 33, metapneumovirus 16, and coronavirus 8. No link was found between virologic results and clinical outcome. A strong link was found between the rate of influenza virus positivity and the incidence of flu-like illness in the community (p=0.017). CONCLUSION: These results show that respiratory virus infection—particularly influenza virus infection during epidemic periods—is common among patients hospitalized for acute cardiorespiratory failure.


title: Intussusception in an infant as a manifestation of COVID-19

text: Gastrointestinal manifestations of COVID-19 are rare and have primarily been limited to diarrhea or vomiting. Intussusception is the most common cause of bowel obstruction in infants, with up to 30% of pediatric intussusception cases having a preceding viral illness. We present the rare case of intussusception in a SARS-CoV-2 positive infant. This is the first documented case of survival in a SARS-CoV-2 positive patient presenting with intussusception as the primary manifestation. As our knowledge of this disease evolves, surgeons need to remain suspicious for possible gastrointestinal manifestations of COVID-19.


title: Obesity and impaired metabolic health in patients with COVID-19

text: Preliminary data suggest that people with obesity are at increased risk of severe COVID-19. However, as data on metabolic parameters (such as BMI and levels of glucose and insulin) in patients with COVID-19 are scarce, increased reporting is needed to improve our understanding of COVID-19 and the care of affected patients.


HIV Trends: Defining “The Middle East”


title: Pediatric Resuscitation Practices During the Coronavirus Disease 2019 Pandemic

text: While most pediatric coronavirus disease 2019 cases are not life threatening, some children have severe disease requiring emergent resuscitative interventions. Resuscitation events present risks to healthcare provider safety and the potential for compromised patient care. Current resuscitation practices and policies for children with suspected/confirmed coronavirus disease 2019 are unknown. DESIGN: Multi-institutional survey regarding inpatient resuscitation practices during the coronavirus disease 2019 pandemic. SETTING: Internet-based survey. SUBJECTS: U.S. PICU representatives (one per institution) involved in resuscitation system planning and oversight. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 130 institutions surveyed, 78 (60%) responded. Forty-eight centers (62%) had admitted coronavirus disease 2019 patients; 26 (33%) reported code team activation for patients with suspected/confirmed coronavirus disease 2019. Sixty-seven respondents (86%) implemented changes to inpatient emergency response systems. The most common changes were as follows: limited number of personnel entering patient rooms (75; 96%), limited resident involvement (71; 91%), and new or refined team roles (74; 95%). New or adapted technology is being used for coronavirus disease 2019 resuscitations in 58 centers (74%). Most institutions (57; 73%) are using enhanced personal protective equipment for all coronavirus disease 2019 resuscitation events; 18 (23%) have personal protective equipment policies dependent on the performance of aerosol generating procedures. Due to coronavirus disease 2019, most respondents are intubating earlier during cardiopulmonary resuscitation (56; 72%), utilizing video laryngoscopy (67; 86%), pausing chest compressions during laryngoscopy (56; 72%), and leaving patients connected to the ventilator during cardiopulmonary resuscitation (56; 72%). Responses were varied regarding airway personnel, prone cardiopulmonary resuscitation, ventilation strategy during cardiopulmonary resuscitation without an airway in place, and extracorporeal cardiopulmonary resuscitation. Most institutions (46; 59%) do not have policies regarding limitations of resuscitation efforts in coronavirus disease 2019 patients. CONCLUSIONS: Most U.S. pediatric institutions rapidly adapted their resuscitation systems and practices in response to the coronavirus disease 2019 pandemic. Changes were commonly related to team members and roles, personal protective equipment, and airway and breathing management, reflecting attempts to balance quality resuscitation with healthcare provider safety.


title: The Use of Nanotrap Particles in the Enhanced Detection of Rift Valley Fever Virus Nucleoprotein

text: BACKGROUND: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP), the most abundant and widely used viral protein for RVFV diagnostics. RESULTS: After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours) and at elevated temperatures (at 37ºC). CONCLUSION: This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to a wide range of pathogens and their analytes of diagnostic interest.


title: Europe, the bull and the Minotaur: the biological legacy of a Neolithic love story

text: The European cattle was domesticated 10 000 years ago in eastern Turkey, 1000 years later pottery‐associated milk fats identify cattle‐based dairy activity in western Turkey. Subsequently, the Indo‐European language, domesticated animals and plants travel as a Neolithic package along two major routes across Europe. A striking south‐east to north‐west gradient of a mutation in the current European population (lactase persistence into adulthood) documents the expansion of a Neolithic dairy culture into a Mesolithic hunter society. Using oral tradition (myths), archaeological and written historical evidence and biological data, it is asked whether highly transmissible viral diseases like measles and smallpox entered during the Neolithic from domesticated animals into the human population. The bovine origin of paramyxovirus infections is likely; smallpox comes from camels or from rodents via cattle while mycobacteria and Helicobacter infected humans already before the Neolithic. Microbes adapt constantly and quickly to changing ecological situations. The current global environmental changes will lead to another highly dynamic phase of viral transmissions into the human population.


title: Development of Antibody Therapeutics against Flaviviruses

text: Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates.


title: Structural characterization by transmission electron microscopy and immunoreactivity of recombinant Hendra virus nucleocapsid protein expressed and purified from Escherichia coli

text: Abstract Hendra virus (family Paramyxoviridae) is a negative sense single-stranded RNA virus (NSRV) which has been found to cause disease in humans, horses, and experimentally in other animals, e.g. pigs and cats. Pteropid bats commonly known as flying foxes have been identified as the natural host reservoir. The Hendra virus nucleocapsid protein (HeV N) represents the most abundant viral protein produced by the host cell, and is highly immunogenic with naturally infected humans and horses producing specific antibodies towards this protein. The purpose of this study was to express and purify soluble, functionally active recombinant HeV N, suitable for use as an immunodiagnostic reagent to detect antibodies against HeV. We expressed both full-length HeV N, (HeV NFL), and a C-terminal truncated form, (HeV NCORE), using a bacterial heterologous expression system. Both HeV N constructs were engineered with an N-terminal Hisx6 tag, and purified using a combination of immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC). Purified recombinant HeV N proteins self-assembled into soluble higher order oligomers as determined by SEC and negative-stain transmission electron microscopy. Both HeV N proteins were highly immuno-reactive with sera from animals and humans infected with either HeV or the closely related Nipah virus (NiV), but displayed no immuno-reactivity towards sera from animals infected with a non-pathogenic paramyxovirus (CedPV), or animals receiving Equivac® (HeV G glycoprotein subunit vaccine), using a Luminex-based multiplexed microsphere assay.


title: Lights and Colours: Science, Techniques and Surveillance for the Future – 4(th) IC3EM 2020, Caparica, Portugal

text: • Special Issue on 4th IC(3)EM 2020. • Science, Techniques, Surveillance. • The importance of Science. • Fluorescent dyes.


docid: difoussm

title: Infectious diseases and regional security in east Asia


Urología en tiempos de pandemia


title: Signaling pathways involved in liver injury and regeneration in rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure

text: Management of fulminant hepatic failure (FHF) continues to be one challenging problem, and experimental animal models resembling its clinical conditions are still needed. Rabbit hemorrhagic disease (RHD) fullfils many requirements of an animal model of FHF. This work investigated changes in MAPK, NF-κB, AP-1 and STAT pathways during RHD-induced liver injury. Rabbits were infected with 2 × 10(4) hemagglutination units of an RHD virus isolate. Apoptosis was documented by the presence of caspase-3 activity and substantial PARP proteolysis at 36 and 48 h postinfection (pi). Infection induced a marked and maintained expression of TNF-α from 12 h pi, while there was only a transitory increase in IL-6 expression. Expression of phosphorylated (p)-JNK, p-p38 and p-ERK1/2 was significantly elevated at 12 h pi. At 48 h pi p-JNK expression was maintained at a maximum level, while that of p-p38 returned to normality and there was no p-ERK1/2 expression. Activation of NF-κB and AP-1 and increased expression of VCAM-1 and COX-2 were observed. No significant changes were detected in activation of STAT1 and STAT3, while SOCS3 expression increased significantly. The current findings suggest that activation of JNK is an essential component in liver injury mediated by the RHD virus and that lack of activation of STAT3, probably mediated by SOCS3 over-expression, would contribute to the inhibition of the regenerative response. Data show the presence of molecular mechanisms contributing to liver damage and the lack of regeneration and they support the usefulness of this model to investigate novel therapeutical modalities in FHF.


title: The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells

text: Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.


title: Genetic architecture of host proteins interacting with SARS-CoV-2

text: Strategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid ‘in silico’ assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01–49.9%) and explaining 0.3–70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).


title: Distinct Epitopes on CD13 Mediate Opposite Consequences for Cell Adhesion

text: CD13 is a membrane glycoprotein with aminopeptidase activity, expressed on several cell types, including myeloid cells (dendritic cells, monocytes, macrophages, neutrophils, etc.). CD13 participates in several functions such as proteolytic regulation of bioactive peptides, viral receptor, angiogenesis, and tumor metastasis. CD13 has also been proposed to participate in cell adhesion, as crosslinking of CD13 by certain CD13-specific antibodies induces homotypic aggregation of monocytes and heterotypic adhesion of monocytes to endothelial cells. We generated two monoclonal antibodies (mAbs C and E) that block homotypic aggregation of U-937 monocytic cells induced by CD13-specific mAb 452. Moreover, the mAbs cause detachment of cells whose aggregation was induced by CD13 crosslinking. Both mAbs also inhibit heterotypic adhesion of U-937 monocytes to endothelial cells. mAbs C and E recognize membrane CD13 but bind to epitopes different from that recognized by mAb 452. Crosslinking of CD13 by mAb C or E is required to inhibit adhesion, as monovalent Fab fragments are not sufficient. Thus, C and E antibodies recognize a distinct epitope on CD13, and binding to this epitope interferes with both CD13-mediated cell adhesion and enzymatic activity. These antibodies may represent important tools to study cell-cell interactions mediated by CD13 in physiological and pathological conditions.


title: A mild type of childhood Covid-19 - A case report

text: Abstract This case is about a 9-year-old child diagnosed with COVID-19, with a history of epidemiology; SARS-CoV-2 nucleic acids testing was positive, while chest CT examination was negative. The clinical classification was light. Nonetheless, isolation measures should still be taken to avoid infecting others.


title: Contagion effect of COVID‐19 outbreak: Another recipe for disaster on Indian economy

text: The global outbreak of COVID‐19 and subsequent lockdowns raises serious economic concern and havoc worldwide. This article tries to provide an economic perspective of COVID‐19 in India using some statistical figure of economic indicators. Analysis is based on the data collected for macro‐economy, travel & tourism, transportation, stock market, human capital and trade. Finding revel that India could experience a health debacle at present and excruciating economic contraction in the near future if the government is unable to execute a proper policy framework. Based on the discussion, a few policy suggestions have been presented to counter both health and economic crisis.


COVID‐19 and (hydroxy)chloroquine–azithromycin combination: Should we take the risk for our patients?