title: Sintomatología gastrointestinal en las infecciones respiratorias agudas de etiología viral

text: Resumen Objetivo Estudiar las diferencias en la sintomatología de las infecciones respiratorias virales confirmadas por laboratorio, especialmente en cuanto a las manifestaciones clínicas de gastroenteritis, en función de la edad y el tipo de virus aislado, durante 5 temporadas gripales, de 1999 a 2004. Material y métodos El período de estudio ha sido de 5 temporadas gripales, desde 1999-2000 hasta 2003-2004. Se revisaron los informes de recogida de datos correspondientes a las muestras obtenidas por 24 equipos de atención primaria distribuidos por el territorio de Cataluña, con resultados positivos para alguno de los virus estudiados (virus de la gripe A [VGA], virus de la gripe B [VGB], virus respiratorio sincitial [VRS] y adenovirus [ADV]). Se estudiaron las siguientes variables clínicas: inicio brusco, fiebre, sintomatología respiratoria, odinofagia, artromialgias, sintomatología gastrointestinal para cada tipo de virus en 2 grupos de edad: menores o iguales y mayores de 14 años. Como medidas de asociación se calcularon las odds ratio (OR) y sus intervalos de confianza (IC) del 95%. Resultados Del total de 1.591 muestras analizadas durante las 5 temporadas gripales estudiadas, un 42,68% (679) de las muestras obtenidas procedía de pacientes cuya edad era ≤ 14 años y el 57,32% (912) pertenecía a pacientes>14 años de edad. Se obtuvieron 286 positividades a VGA (166/286 [58,04%] en≤14 años, y 120/286 [41,95%] en>14 años), 107 muestras positivas a VGB (78/107 [72,90%] en≤14 años y 29/107 [27,10%] en>14 años), 53 a VRS (39/53 [73,58%] en≤14 años y 12/53 [22,64%] en>14 años) y 40 a ADV (36/40 [90%] en≤14 años y 4/40 [10%] en>14 años). Las diferencias de sintomatología entre ambos grupos de edad se pudieron comparar para el VGA, la fiebre (OR=16,536; IC del 95%, 4,893-55,887; p=0,001) y la sintomatología gastrointestinal (OR=4,664; IC del 95%, 1,569-13,868; p<0,036) resultaron ser significativamente más frecuentes en los ≤ 14 años que en los mayores de esa edad, mientras que las artromialgias (OR=0,048; IC del 95%, 0,026-0,089; p=0,001) lo fueron para los mayores de 14 años. Conclusiones Los datos obtenidos en este trabajo indican que entre las manifestaciones clínicas de las infecciones respiratorias agudas de etiología viral en la población pediátrica, a diferencia de lo que ocurre en la población adulta, la fiebre se encuentra asociada a todos los virus estudiados mientras que los síntomas gastrointestinales se asocian, en mayor grado, a las infecciones producidas por virus de la gripe A y B y que el grupo de edad de<5 años es el que muestra una mayor frecuencia de dichos síntomas. Abstract Objective To study differences in the presentation of laboratory-confirmed acute viral respiratory infections, especially gastroenteritis symptoms, according to age and causative viral agent during five influenza seasons (1999 to 2004.) Material and methods Five influenza seasons (1999-2000 to 2003-2004) were studied. Data from samples taken at 24 primary care sentinel centres for influenza surveillance distributed throughout Catalonia (Spain), which were positive for any of the viruses studied (influenza virus A, [IVA], influenza virus B [IVB], syncytial respiratory virus [SRV], adenovirus [ADV] and parainfluenza 1,2,3 viruses), were analyzed. The following clinical variables were evaluated: sudden onset, fever, respiratory symptoms, sore throat, malaise and gastrointestinal symptoms. These variables were studied for each virus and for two age groups: age 14 years or younger and older than 14 years. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Of a total of 1,591 samples tested during the influenza seasons studied, 42.68% (679) samples belonged to subjects aged ≤ 14 years and 57.32% (912) to subjects aged>14 years. There were 286 IVA (166/286 [58.04%] in subjects aged ≤ 14 years and 120/286 [41.95%] in subjects aged>14 years), 107 were positive for IVB (78/107 [72.90%] in subjects aged ≤ 14 years and 29/107 [27.10%] in subjects aged>14 years), 53 SRV (39/53 [73.58%] in subjects aged ≤ 14 years and 12/53 [22.64%] in subjects aged>14 years) and 40 ADV (36/40 [90%] in subjects aged ≤ 14 years and 4/40 [10%] in subjects aged>14 years). The differences in symptoms between the two age groups could be compared for IVA: fever (OR=16.536; 95% CI=4.893-55.887; p=0.001) and gastrointestinal symptoms (OR=4.664; 95% CI=1.569-13.868; p<0.03) were significantly more frequent in subjects aged ≤ 14 years, while malaise (OR=0.048; 95% CI=0.026-0.089; p=0.001) was more frequent in subjects aged>14 years. Conclusions The results indicate that acute viral respiratory infections always present with fever in children, whatever the virus, but not in adults. Gastrointestinal symptoms were more strongly associated with IVA and IVB and these symptoms were most frequent in children aged under 5 years.


title: An Episulfide Cation (Thiiranium Ring) Trapped in the Active Site of HAV 3C Proteinase Inactivated by Peptide-based Ketone Inhibitors

text: Abstract We have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 Å, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the β-hairpin motif (residues 138–158), an extension of two β-strands of the C-terminal β-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sγ of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase.


title: Alberta family physicians’ willingness to work during an influenza pandemic: a cross-sectional study

text: OBJECTIVE: Effective pandemic responses rely on frontline healthcare workers continuing to work despite increased risk to themselves. Our objective was to investigate Alberta family physicians willingness to work during an influenza pandemic. Design: Cross-sectional survey. Setting: Alberta prior to the fall wave of the H1N1 epidemic. Participants: 192 participants from a random sample of 1000 Alberta family physicians stratified by region. Main Outcome Measures: Willingness to work through difficult scenarios created by an influenza epidemic. RESULTS: The corrected response rate was 22%. The most physicians who responded were willing to continue working through some scenarios caused by a pandemic, but in other circumstances less than 50% would continue. Men were more willing to continue working than women. In some situations South African and British trained physicians were more willing to continue working than other groups. CONCLUSIONS: Although many physicians intend to maintain their practices in the event of a pandemic, in some circumstances fewer are willing to work. Pandemic preparation requires ensuring a workforce is available. Healthcare systems must provide frontline healthcare workers with the support and resources they need to enable them to continue providing care.


Editorial: Zika Virus Research


Potential Inhibition of COVID-19-driven Pneumonia by Immunosuppressive Therapy and anti-TNFα Antibodies: A Case Report


Retraction—Chinese medical staff request international medical assistance in fighting against COVID-19


title: Influence of meteorological factors and air pollution on the outbreak of severe acute respiratory syndrome

text: Summary Objectives To understand the association between the outbreak of severe acute respiratory syndrome (SARS) and meteorological factors and air pollution. Study design An ecological study was conducted. Methods Three hundred and fifty primary probable SARS cases diagnosed in mainland China between 1 January and 31 May 2003, and their 6727 close contacts during the period of their clinical symptoms before admission, were included in this study. Of the 6727 close contacts, 135 (2.0%) later developed clinical symptoms and were diagnosed as probable SARS cases. The daily meteorological data and daily air pollution data during the same SARS outbreak period in mainland China were used in the data analysis. Logistic regression analyses were conducted to explore the association between the secondary attack rate of SARS and meteorological factors and air pollution. Results In univariate analyses, daily average temperature (DAT), daily average air pressure (DAAP), and daily average relative humidity (DARH) were inversely associated with secondary attack rate (P<0.001); a significant positive association was found for daily hours of sunshine (DHS) (P<0.001). In multivariate analyses, factors associated with secondary attack rate were DAAP (odds ratio (OR)=0.53, 95% confidence interval (CI): 0.42, 0.66), DARH (OR=0.73, 95% CI: 0.53, 1.00), and daily average wind velocity (DAWV; OR=0.81, 95% CI: 0.68, 0.96). Adjustment for the onset time of a primary case led to little change in the results. In addition, in Hebei Province, a major affected area in China, only DAWV (OR=0.38, 95% CI: 0.20, 0.72) was a significant predictor of secondary attack rate with adjustment for the onset time of primary case. In Inner Mongolia, another major affected area in China, DAWV (OR=0.50, 95% CI: 0.26, 0.94) and DHS (OR=0.27, 95% CI: 0.09, 0.81) were significant predictors of secondary attack rate with adjustment for the onset time of primary case. Conclusions Our results suggest that the SARS outbreak was significantly associated with DAWV, and that DAAP, DARH and DHS may also have influenced the SARS outbreak to some extent. However, because of ecological fallacy and uncontrolled confounding effects that may have biased the results, the association between the SARS outbreak and these meteorological factors and air pollution deserve further investigation.


title: Self-assembling Prodrug Nanotherapeutics for Synergistic Tumor Targeted Drug Delivery

text: Abstract Self-assembling prodrugs represents a robust and effective nanotherapeutic approach for delivering poorly soluble anticancer drugs. With numerous intrinsic advantages, self-assembling prodrugs possess the maximum drug loading capacity, controlled drug release kinetics, prolonged blood circulation, and preferential tumor accumulation based on the enhanced permeability and retention (EPR) effect. These prodrug conjugates allow for efficient self-assembly into nanodrugs with the potential of encapsulating other therapeutic agents that have different molecular targets, enabling simultaneous temporal-spatial release of drugs for synergistic antitumor efficacy with reduced systemic side effects. The aim of this review is to summarize the recent progress of self-assembling prodrug cancer nanotherapeutics that are made through conjugating therapeutically active agents to Polyethylene glycol, Vitamin E, or drugs with different physicochemical properties via rational design, for synergistic tumor targeted drug delivery.


title: Zoonoses and One Health: A Review of the Literature

text: Background. One health is a concept that was officially adopted by international organizations and scholarly bodies in 1984. It is the notion of combining human, animal, and environmental components to address global health challenges that have an ecological interconnectedness. Methods. A cross-sectional study of the available literature cited was conducted from January 1984 when the one health concept was adopted till December 2012 to examine the role of the one health approach towards zoonoses. Inclusion criteria included publications, professional presentations, funding allocations, official documentation books, and book chapters, and exclusion criteria included those citations written outside the period of review. Results. A total of 737 resources met the inclusion criteria and were considered in this review. Resources showed a continuous upward trend for the years from 2006 to 2012. The predominant resources were journal publications with environmental health as the significant scope focus for one health. There was also an emphasis on the distribution of the work from developed countries. All categories of years, resources, scopes, and country locale differed from the means (P = 0.000). Year of initiative, scope, and country locale showed a dependent relationship (P = 0.022, P = 0.003, and P = 0.021, resp.). Conclusion. Our findings demonstrate the rapid growth in embracing the concept of one health, particularly in developed countries over the past six years. The advantages and benefits of this approach in tackling zoonoses are manifold, yet they are still not seemingly being embraced in developing countries where zoonoses have the greatest impact.


title: An Updated Loop-Mediated Isothermal Amplification Method for Rapid Diagnosis of H5N1 Avian Influenza Viruses

text: We designed a new set of primers for reverse transcriptase loop-mediated isothermal amplification (RTLAMP) to specifically amplify the HA gene of avian influenza viruses subtype H5N1. By testing nine H5N1 virus strains and 41 clinical samples collected in Northern Vietnam, we found that the new primers showed higher sensitivity and specificity than the previously published RT-LAMP primers and were comparable to the RT-PCR method currently recommended by WHO. These results suggest that our RT-LAMP assay may be a better choice as a diagnostic tool for current H5N1 influenza virus infection.


title: Mesodynamics in the SARS nucleocapsid measured by NMR field cycling

text: Protein motions on all timescales faster than molecular tumbling are encoded in the spectral density. The dissection of complex protein dynamics is typically performed using relaxation rates determined at high and ultra-high field. Here we expand this range of the spectral density to low fields through field cycling using the nucleocapsid protein of the SARS coronavirus as a model system. The field-cycling approach enables site-specific measurements of R (1) at low fields with the sensitivity and resolution of a high-field magnet. These data, together with high-field relaxation and heteronuclear NOE, provide evidence for correlated rigid-body motions of the entire β-hairpin, and corresponding motions of adjacent loops with a time constant of 0.8 ns (mesodynamics). MD simulations substantiate these findings and provide direct verification of the time scale and collective nature of these motions.


title: SARS-CoV-2 pandemic: An Emerging Public Health Concern for the Poorest in Bangladesh

text: Abstract The novel coronavirus (SARS-CoV-2) pandemic is now a global crisis and the poorest in Bangladesh are the most vulnerable. With the whole country being subjected to lockdown measures, millions of poor people are unable to go to work and have lost their incomes, leaving them in profound poverty without access to food and basic health services. Furthermore, living in cramped conditions, lack of health awareness, basic hygiene practices, and failing to maintain social distance measures which are inherently present among the poor, put them at an increased risk of SARS-CoV-2 infection. As the pandemic threatens to expand its devastating grip on Bangladesh, the government and the aid organizations must make urgent and comprehensive initiatives to assist those most in need in this unprecedented health crisis.


title: Diagnosis of Liver Disease in Domestic Ferrets (Mustela Putorius)

text: Liver disease in ferrets is often subclinical and underdiagnosed. Clinical pathology and diagnostic imaging are needed to guide clinicians but definite diagnosis is based on histopathologic lesions. Inflammatory digestive conditions can lead to ascending tract infection and hepatobiliary inflammation. Ferrets have a specific sensitivity to hepatic lipidosis. Incidence of hepatic neoplasia is high in ferrets. After a summary of anatomy and physiology of the ferret liver, hepatic diseases known in ferret species are reviewed with their subsequent diagnostic procedures.


title: SARS-CoV Replication and Pathogenesis in an In Vitro Model of the Human Conducting Airway Epithelium

text: SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The severe and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough and persistent high fever in cases of severe acute respiratory virus brought to light the importance of coronaviruses as potentially lethal human pathogens and the identification of several zoonotic reservoirs has made the reemergence of new strains and future epidemics all the more possible. In this chapter, we describe the pathology of SARS-CoV infection in humans and explore the use of two models of the human conducting airway to develop a better understanding of the replication and pathogenesis of SARS-CoV in relevant in vitro systems. The first culture model is a human bronchial epithelial cell line Calu3 that can be inoculated by viruses either as a non-polarized monolayer of cells or polarized cells with tight junctions and microvilli. The second model system, derived from primary cells isolated from human airway epithelium and grown on Transwells, form a pseudostratified mucociliary epithelium that recapitulates the morphological and physiological features of the human conducting airway in vivo. Experimental results using these lung epithelial cell models demonstrate that in contrast to the pathology reported in late stage cases SARS-CoV replicates to high titers in epithelial cells of the conducting airway. The SARS-CoV receptor, human angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical surface of cells in polarized Calu3 cells and human airway epithelial cultures (HAE), indicating that hACE2 was accessible by SARS-CoV after airway lumenal delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway epithelial cells. In support of the hACE2 localization data, the most productive route of inoculation and progeny virion egress in both polarized Calu3 and ciliated cells of HAE was the apical surface suggesting mechanisms to release large quantities of virus into the lumen of the human lung. Preincubation of the apical surface of cultures with antisera directed against hACE2 reduced viral titers by 2 logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral replication levels suggesting that hACE2 is the primary receptor for entry of SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in ciliated airway cultures derived from susceptible animal species we generated a recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/b) and insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS-CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures generated from Golden Syrian hamster tracheas reached similar titers to the human cultures by 72 hours post infection. Efficient SARS-CoV infection of ciliated cell-types in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.


title: Evaluation of a specialized filter-paper matrix for transportation of extended bovine semen to screen for bovine herpesvirus-1 by real-time PCR

text: Abstract The extended frozen semen (EFS) batches produced from infectious bovine rhinotracheitis (IBR) sero-positive cattle and buffalo bulls housed in various semen stations in India are transported to the testing laboratory in liquid nitrogen (LN2) for screening bovine herpesvirus-1 (BoHV-1). This procedure is laborious and poses LN2 related hazards. An alternative logistics for transportation of samples was investigated. Use of Flinders Technology Associates (FTA®) elute card was evaluated for transportation of extended bovine semen to screen BoHV-1 DNA by real-time PCR targeting gB gene and the method was compared with the OIE approved Chelex resin based method. A protocol for extraction of BoHV-1 DNA from FTA® card spotted with extended semen was optimized. The viral DNA was found to be stable on FTA® card for at least 28 days when the cards are stored at 4°–37 °C. The analytical sensitivity for the assay was determined using variable dilutions of BoHV-1 spiked semen and positive plasmid harbouring gB gene (97bp) spotted onto FTA® card and it was found to be 100.8 TCID50/ml or 100 copies respectively in real-time PCR. The test could detect as low as 100.008 TCID50/ml or 1 copy of positive plasmid when more number of replicates (n = 6) of the same sample were tested. This sensitivity was found to be comparable to Chelex method and both the methods demonstrated a very strong correlation (r = 0.9774; 95% CI: 0.9620–0.9860) in terms of Ct value (p < 0.0001). The diagnostic sensitivity and specificity of the FTA method in comparison to the Chelex method was 83.08% (95% CI: 71.73%–91.24%) and 93.23% (95% CI: 89.38%–96.01%) respectively when 316 samples were screened by both the methods. The degree of agreement between these two tests was good (Kappa value: 0.738; 95% CI: 0.646–0.829). The method was found to be robust and highly repeatable in inter-assay and intra-assay precision testing. The result suggests that the FTA® card holds promise as an alternative system for transportation of EFS for downstream screening of BoHV-1 DNA.


title: Declining Influenza Vaccination Coverage among Nurses, Hong Kong, 2006–2012

text: Seasonal influenza vaccination of nurses in Hong Kong fell from 57% in 2005 to 24% in 2012, paralleling concern for adverse reactions associated with vaccination. Decreased acceptance of vaccination was most prominent among nurses who had less work experience and more frequent contact with patients.


title: Group Testing-Based Robust Algorithm for Diagnosis of COVID-19

text: At the time of writing, the COVID-19 infection is spreading rapidly. Currently, there is no vaccine or treatment, and researchers around the world are attempting to fight the infection. In this paper, we consider a diagnosis method for COVID-19, which is characterized by a very rapid rate of infection and is widespread. A possible method for avoiding severe infections is to stop the spread of the infection in advance by the prompt and accurate diagnosis of COVID-19. To this end, we exploit a group testing (GT) scheme, which is used to find a small set of confirmed cases out of a large population. For the accurate detection of false positives and negatives, we propose a robust algorithm (RA) based on the maximum a posteriori probability (MAP). The key idea of the proposed RA is to exploit iterative detection to propagate beliefs to neighbor nodes by exchanging marginal probabilities between input and output nodes. As a result, we show that our proposed RA provides the benefit of being robust against noise in the GT schemes. In addition, we demonstrate the performance of our proposal with a number of tests and successfully find a set of infected samples in both noiseless and noisy GT schemes with different COVID-19 incidence rates.


title: Complications des tatouages : informations récentes justifiant la prise de mesures urgentes

text: Resume Les tatouages cutanés sont pratiqués depuis fort longtemps mais leur toxicité reste peu connue du grand public qui a de plus en plus recours à ces techniques sans être informé des risques encourus, infectieux, allergiques, dermatologiques, toxiques systémiques et même ophtalmologiques. Cette situation est aggravée par la mode des tatouages « corps entier ». Cette séance dédiée est une mise au point des risques encourus liés aux tatouages Summary Skin tattoos have been used for a long time but their toxicity remains little known to the general public who increasingly resort to these techniques without being informed of the risks involved, infectious, allergic, dermatological, systemic toxic and even ophthalmological. This situation is compounded by the fashion for "whole body" tattoos. This dedicated session is an update on the risks associated with tattoos


title: Extreme Events in a Globalized Food System

text: Our food systems are complex and globally interdependent and are presently struggling to feed the world’s population. As population grows and the world becomes increasingly unstable and subject to shocks, it is imperative that we acknowledge the systemic nature of our food system and enhance its resilience.


title: 5′-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity

text: RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade.


title: A Butterfly Flaps its Wings: Extinction of Biological Experience and the Origins of Allergy

text: OBJECTIVE: The grand global challenges of the Anthropocene are interdependent with ample evidence that reduced early-life ‘experience’ of biodiversity primes for immune dysregulation and a higher propensity low-grade inflammation, increasing the risk of allergy many other later-onset NCDs —also now implicated in the susceptibility to acute inflammation in COVID-19 infection. The objective of this review is to explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation. DATA SOURCES: Were identified from PubMed and Web of Science using search terms pertaining to biodiversity, nature-relatedness, allergic disease, microbiome, NCDs, COVID-19 and associated terms. STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity. RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects from allergy and both acute and chronic inflammatory disorders. These important links to eco-psychological constructs of the ‘extinction of experience’ which indicates that loss of direct, personal contact with biodiversity—wildlife and the more visible elements of the natural world—might lead to emotional apathy and irresponsible behaviors toward the environment. CONCLUSION: The immune system is a useful early barometer of environmental impacts, and via the microbiome, a measure of the way in which our current experiences differ from our ancestral past. While we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspect of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, physical activity, and promotes environmental responsibility.


title: Prolonged nasal eosinophilia in all_ergic patients after common cold

text: Background: Viral respiratory tract infections may cause both harmless common colds and severe asthma exacerbations; the differences in disease expression probably depend on the all_ergic status of the patient. To determine whether altered immunologic mechanisms underlie these differences, we investigated nasal inflammation during naturall_y acquired common cold. Methods: In a group of 16 patients (eight all_ergic), nasal brush samples were taken, and nasal symptoms were recorded during common cold, 2 weeks later (convalescence), and at baseline (>4 weeks without nasal symptoms). Nasal brush cells were stained immunohistochemicall_y for Langerhans cells, T cells, monocytes, neutrophils, B cells, macrophages, natural killer (NK) cells, mast cells, eosinophils, eotaxin, and RANTES. Results: Four rhinovirus, four coronavirus, three RSV, one Mycoplasma pneumoniae, and one influenza A/enterovirus double infection were confirmed. Increased numbers of T cells, monocytes, macrophages, NK cells, eosinophils, and RANTES‐ and eotaxin‐positive cells, but not neutrophils, were observed during common cold in all_ergic and nonall_ergic patients, and increased numbers of mast cells in all_ergic patients. Compared to nonall_ergic patients, in all_ergic patients eosinophil influx persisted into convalescence. Conclusions: Prolonged nasal eosinophil influx was observed in all_ergic patients after common cold. What immunologic factors can induce prolonged eosinophil influx and whether this may increase the risk of subsequent all_ergen‐induced hypersensitivity reactions must be studied further.


title: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID‐19?

text: The recent 2019‐novel coronavirus (2019‐nCoV, also known as SARS‐CoV‐2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID‐19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019‐nCoV. Prior to the present pandemic of COVID‐19, there have been multiple large‐scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face‐to‐face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.


title: COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways

text: Abstract Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.


title: Evaluation of 10 serological assays for diagnosing Mycoplasma pneumoniae infection

text: Abstract In this study, the performance of 10 serological assays for the diagnosis of Mycoplasma pneumoniae infection was evaluated. A total of 145 sera from 120 patients were tested. They were obtained from patients who were serologically positive for M. pneumoniae infection as well as from patients who were infected with micro-organisms that may cause interstitial pneumonia. The following assays were utilized: SeroMP IgM and IgG, SeroMP recombinant IgM, IgA and IgG, Liaison M. pneumoniae IgM and IgG and M. pneumoniae IgM, IgA and IgG ELISA Medac. The SeroMP Recombinant and Liaison assays both showed low IgM specificity, and crossreactivity was mainly observed in groups of patients with acute cytomegalovirus and Epstein-Barr virus infections. For IgA, the Medac assay was less specific than the SeroMP Recombinant assay. Discrepancies between the four tests were observed in IgG analyses, and due to the lack of a gold standard, 22 results were removed prior to determining the sensitivity and specificity. Therefore, the overall performance of IgG assays may be overstated; nevertheless, the SeroMP assay demonstrated a lack of sensitivity. The seroprevalence of IgG appears to be very low, raising concerns regarding whether the serological techniques can detect IgG levels over time. Serology remains a biological tool of choice for diagnosing M. pneumoniae infection, but improvement and standardization of the assays are needed, particularly for the determination of IgG.


title: Reverse Genetic Approaches for the Generation of Recombinant Zika Virus

text: Zika virus (ZIKV) is an emergent mosquito-borne member of the Flaviviridae family that was responsible for a recent epidemic in the Americas. ZIKV has been associated with severe clinical complications, including neurological disorder such as Guillain-Barré syndrome in adults and severe fetal abnormalities and microcephaly in newborn infants. Given the significance of these clinical manifestations, the development of tools and reagents to study the pathogenesis of ZIKV and to develop new therapeutic options are urgently needed. In this respect, the implementation of reverse genetic techniques has allowed the direct manipulation of the viral genome to generate recombinant (r)ZIKVs, which have provided investigators with powerful systems to answer important questions about the biology of ZIKV, including virus-host interactions, the mechanism of transmission and pathogenesis or the function of viral proteins. In this review, we will summarize the different reverse genetic strategies that have been implemented, to date, for the generation of rZIKVs and the applications of these platforms for the development of replicon systems or reporter-expressing viruses.


title: Interleukin-35 on B cell and T cell induction and regulation

text: Interleukin (IL)-35 is a relatively newly discovered member of IL-12 cytokine family that is unique in that it is a dimer formed by two subunits. The review documents the structure, secretion and signal transduction of IL-35, the regulation effect of IL-35 on B cells and T cells as well as the adoptive transfer of IL-35+ regulatory B cells (Breg), therapeutic prospects of recombinant IL-35 (rIL-35) and IL-35 regulation role in various diseases. B-cell regulation expands the regulatory range of IL-35 and alters the view that IL-10 is the chief immune mechanism for Breg cells which secrete IL-35. IL-35 induces Breg cells, which then can induce Treg cells. IL-35 also plays an immunomodulatory role in the human body.


title: Emerging tick-borne infections in mainland China: an increasing public health threat

text: Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.


title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques

text: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.


title: SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China

text: This cross-sectional study reviews the medical records of 1524 patients with cancer treated at a single tertiary care hospital in Wuhan, China to evaluate the characteristics associated with transmission of the SARS-CoV-2 virus.


title: Effects of relative humidity on animal health and welfare

text: Abstract Farm animals are sources of meat, milk and eggs for the humans, and animal health ensures the quality and security of these agricultural and sideline products. The animal raising conditions in livestock stations and poultry houses play vital roles in both animal health and production. One of the major factors affecting raising conditions, relative humidity, has not received much attention even though it is important for animal husbandry. In this review, we summarize the impacts of relative humidity on animal health and welfare to draw attention for its importance in the improvement of animal raising conditions in the future.


title: Anthropogenic gadolinium in freshwater and drinking water systems

text: The increasing use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging is leading to widespread contamination of freshwater and drinking water systems. Contrary to previous assumptions that GBCAs are stable throughout the water cycle, they can degrade. The stability of GBCAs depends largely on their organic ligands, but also on the physicochemical conditions. There is specific concern regarding UV end-of-pipe water treatments, which may degrade GBCAs. Degradation products in drinking water supplies can increase the risk of adverse health effects. This is of particular relevance where the raw water for drinking water production has a higher proportion of recycled wastewater. GBCAs concentrations in aquatic systems, often referred to as anthropogenic gadolinium, are determined using a variety of calculation methods. Where anthropogenic gadolinium concentrations are low, the inconsistent use of these methods results in high discrepancies and high levels of uncertainty. The current COVID-19 crisis will, in the short-term, drastically decrease the input of GBCAs to freshwater systems. Temporal variations in anthropogenic gadolinium concentrations in river water can be used to better understand river-aquifer interactions and groundwater flow velocities. Collecting urine from all patients following MRI examinations could be a way forward to halt the generally increasing concentrations of Gd in drinking water systems and recover this technologically critical element.


title: Psychological morbidities and fatigue in patients with confirmed COVID-19 during disease outbreak: prevalence and associated biopsychosocial risk factors

text: OBJECTIVE: The coronavirus disease 2019 (COVID-19) - a novel and highly infectious pneumonia - has now spread across China and beyond for over four months. However, its psychological impact on patients is unclear. We aim to examine the prevalence and associated risk factors for psychological morbidities and fatigue in patients with confirmed COVID-19 infection. METHODS: Amidst the disease outbreak, 41 out of 105 COVID-19 patients in a local designated hospital in China were successfully assessed using a constellation of psychometric questionnaires to determine their psychological morbidities and fatigue. Several potential biopsychosocial risk factors (including pre-existing disabilities, CT severity score of pneumonia, social support, coping strategies) were assessed through multivariable logistic regression analyses to clarify their association with mental health in patients. RESULTS: 43.9% of 41 patients presented with impaired general mental health, 12.2% had post-traumatic stress disorder (PTSD) symptoms, 26.8% had anxiety and/or depression symptoms, and 53.6% had fatigue. We did not find any association between pneumonia severity and psychological morbidities or fatigue in COVID-19 patients. However, high perceived stigmatization was associated with an increased risk of impaired general mental health and high perceived social support was associated with decreased risk. Besides, negative coping inclination was associated with an increased risk of PTSD symptoms; high perceived social support was associated with a decreased risk of anxiety and/or depression symptoms. CONCLUSIONS: Psychological morbidities and chronic fatigue are common among COVID-19 patients. Negative coping inclination and being stigmatized are primary risk factors while perceived social support is the main protective factor.


title: Environmental Factors Affecting the Transmission of Respiratory Viruses

text: Many viruses are capable of infecting the human respiratory tract to cause disease. These viruses display various transmission patterns among humans; however, they all share the ability to transmit from person to person, and their human transmissibility is influenced by the environment in which pathogen and host meet. This review aims to summarize recent and significant observations regarding the impact of environmental factors such as weather and climate, humidity, temperature, and airflow on the transmission of human respiratory viruses. Where possible, knowledge gaps that require further scientific study will be identified.


title: Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds

text: Abstract The 3C-like protease (3CLpro) of SARS-coronavirus mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, becoming an important target for the drug development. In this study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CLpro effects using cell-free and cell-based cleavage assays. Cleavage assays with the 3CLpro demonstrated that IC50 values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC50: 217μM) was more efficient in blocking the cleavage processing of the 3CLpro than indigo (IC50: 752μM) and beta-sitosterol (IC50: 1210μM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro, in which the IC50 was 366μM for aloe emodin and 8.3μM for hesperetin in the cell-based assay.


The COVID-19 Pandemic and Tuberculosis in Taiwan


title: The Middle East Respiratory Syndrome (MERS)

text: The Middle East respiratory syndrome (MERS) is a novel lethal zoonotic disease of humans caused by the MERS coronavirus (MERS-CoV). Although MERS is endemic to the Middle East, travelers have exported MERS-CoV on return to their home countries. Clinical manifestations range from mild to severe acute respiratory disease and death. The elderly, immunocompromised, and those with chronic comorbid liver, lung, and hepatic conditions have a high mortality rate. There is no specific treatment. Person-to-person spread causes hospital and household outbreaks, and thus improved compliance with internationally recommended infection control protocols and rapid implementation of infection control measures are required.


Prognostic Value of Left Ventricular Global Longitudinal Strain in COVID-19


title: In defense of the Desiderata

text: Abstract A 1998 paper that delineated desirable characteristics, or desiderata for controlled medical terminologies attempted to summarize emerging consensus regarding structural issues of such terminologies. Among the Desiderata was a call for terminologies to be “concept oriented.” Since then, research has trended toward the extension of terminologies into ontologies. A paper by Smith, entitled “From Concepts to Clinical Reality: An Essay on the Benchmarking of Biomedical Terminologies” urges a realist approach that seeks terminologies composed of universals, rather than concepts. The current paper addresses issues raised by Smith and attempts to extend the Desiderata, not away from concepts, but towards recognition that concepts and universals must both be embraced and can coexist peaceably in controlled terminologies. To that end, additional Desiderata are defined that deal with the purpose, rather than the structure, of controlled medical terminologies.


title: Creating dementia-friendly and inclusive communities for social inclusion: a scoping review protocol

text: INTRODUCTION: The number of people with dementia is increasing worldwide, with the majority of people with dementia living at home in the community. WHO calls for global action on the public health response to dementia. Social exclusion is commonly reported by people with dementia and their families. Dementia-friendly and inclusive community has emerged as an idea that holds potential to contribute to the mitigation of social exclusion. The objective of the scoping review is to answer two questions: What social inclusion strategies that have been reported in the dementia-friendly and inclusive communities’ literature? What strategies for developing dementia-friendly and inclusive communities that have shown to improve social inclusion? METHODS AND ANALYSIS: This scoping review will follow the Joanna Briggs Institute scoping review methodology and will take place between April and September 2020. The proposed review will consider studies based in community settings with participants living at home with early to late stages of dementia and their families. This includes a three-step search strategy: (1) to identify keywords from MEDLINE and CINAHL; (2) to conduct a second search using all identified keywords and index terms across selected databases (MEDLINE, CINAHL, AgeLine, PsycINFO, Web of Science, ProQuest and Google) and (3) to handsearch the reference lists of all included articles and reports for additional studies. Further, we will search Google for grey literature on published organisational reports. Two researchers will screen titles and abstracts independently and then assess the full text of selected citations against inclusion criteria. Extracted data will be presented in a narrative accompanied by tables that reflect the objective of the review. ETHICS AND DISSEMINATION: As the methodology of this study consists of collecting data from publicly available articles, it does not require ethics approval. This scoping review provides an overview of current evidence on strategies that support dementia-friendly and inclusive communities for social inclusion. The findings will offer insights to inform strategies for education, practice, policy and future research. We will share the scoping review results through conference presentations and an open-access publication in a peer-reviewed journal.


title: Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains

text: The Coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. A combination of sensitive deep sequencing technology and computational algorithms is essential for virus surveillance, especially for characterizing novel- or distantly related virus strains. Here, we explore the use of profile Hidden Markov Model-defined Pfam protein domains (Pfam domains) encoded by new sequences as a Coronaviridae sequence classification tool. The encoded domains are used first in a triage to identify potential Coronaviridae sequences and then processed using a Random Forest method to classify the sequences to the Coronaviridae genus level. The application of this algorithm on Coronaviridae genomes assembled from agnostic deep sequencing data from surveillance of bats and rats in Dong Thap province (Vietnam) identified thirty-four Alphacoronavirus and eleven Betacoronavirus genomes. This collection of bat and rat coronaviruses genomes provided essential information on the local diversity of coronaviruses and substantially expanded the number of coronavirus full genomes available from bat and rats and may facilitate further molecular studies on this group of viruses.


title: Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications

text: OBJECTIVE: Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC). DESIGN: PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project). RESULTS: Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%–2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear. CONCLUSION: PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.


‘Shielded’ anaesthetists and intensivists during the COVID‐19 pandemic


title: Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy

text: Publisher Summary Proteolytic processing of the coronavirus replicase polyproteins is essential for ongoing viral ribonucleic acid (RNA) synthesis. Therefore, the severe acute respiratory syndrome (SARS)-coronaviruses (SARS-CoV) proteases are attractive targets for the development of antiviral drugs to reduce viral replication and pathogenicity. The structure and activity of the coronavirus 3C-like protease (3CLpro) has already been elucidated, and the design of inhibitors to 3CLpro as therapeutics has been proposed. The chapter discusses SARS-CoV 3CLpro inhibitors that include covalent inhibitors, noncovalent inhibitors, and inhibitors from screening. SARS-CoV papain-like protease (PLpro) is considered an equally viable target to 3CLpro for drug design because both are essential for viral replication. However, PLpro has likely not been pursued because of the paucity of structural information. Several compounds have been identified that have shown inhibitory activity against SARS-CoV. However, no information regarding their mechanism of action or the corresponding target is known. Glycyrrhizin showed inhibitory activity for SARS-CoV replication with EC50 = 300 mg/L after virus absorption in Vero cells. Some glycyrrhizin acid derivatives were found to inhibit SARS-CoV replication in vitro with EC50 values ranging from 5 to 50 μM. Unfortunately, these compounds show high cytotoxity.


title: Quelle place et quel avenir pour l’anatomo-cyto-pathologie des maladies infectieuses et tropicales en France ?

text: The management of tissues and cellular samples by the pathologists in the infectious and tropical diseases pathology field in 2014 needs a strong knowledge of both morphological and molecular domains which includes the good control: (i) of the taxonomy of infectious and tropical diseases pathology leading to the pathogens identification and (ii) of the ancillary methods which can be used in fixed samples in order to detect or better identify these pathogens. There is a recent paradox in France concerning the frequency of infectious diseases to be diagnosed in pathology laboratories and the progressive loss of pathologist's expertise in this domain. Different reasons could explain this statement including the omnipresence of the tumour lesions to be managed in a pathology laboratory as well as the recent constraints associated with the different biomarkers that are mandatory to be detected by immunohistochemistry and/or by molecular biology. Even if the microbiologists play a pivotal role for identifying the different pathogens as well as for the assessment of their sensitivity to the anti-microbial drugs, a large number of infectious diseases can be diagnosed only on fixed tissue and/or cells by the pathologists. The purpose of this review is to describe the current and future issues of infectious and tropical diseases diagnoses in pathology laboratories, in particular in France.


title: Blocking CC Chemokine Receptor (CCR) 1 and CCR5 During Herpes Simplex Virus Type 2 Infection In Vivo Impairs Host Defence and Perturbs the Cytokine Response

text: Elimination of viral infections is dependent on rapid recruitment of leucocytes to infected areas. Chemokines constitute a class of cytokines that regulate migration of leucocytes to sites of infection. In this work, the expression and function of CC chemokine receptor (CCR)1 and CCR5 and their ligands during a generalized herpes simplex virus type 2 (HSV‐2) infection in mice were studied. Many CCR1 and CCR5 ligands were expressed in infected organs after intraperitoneal infection. In particular, CC chemokine expression in the liver preceded the expression of CCR1 and CCR5, suggesting recruitment of cells bearing these receptors, which correlated with a decrease in viral titres. Administration of Met‐RANTES, a CCR1 and CCR5 antagonist, led to impaired antiviral response with significantly higher viral titre in the liver on days 1 and 6 after infection. This observation was accompanied by a decreased and shortened recruitment of natural killer cells to the peritoneum of infected mice treated with the antagonist. Despite this reduced recruitment of antiviral leucocytes in mice receiving Met‐RANTES, peritoneal cells from these mice produced markedly enhanced levels of pro‐inflammatory cytokines. Altogether, the results suggest that CCR1 and/or CCR5 are important for both viral clearance and eventual control of the immune response.


title: Chapter 5 Innate Immunity

text: Abstract Two major forms of immune defense are activated once a virus has breached a natural barrier to entry, innate and adaptive immunity. This chapter deals with the innate immune response, a mechanism that operates immediately to limit tissue injury and prevent the spread of virus to adjacent, healthy cells, the so-called “bystander” effect. Innate immunity is of broad specificity, modulated largely by the secretion of an extensive array of signaling molecules that collectively form local inflammatory responses. Almost all viruses have developed elaborate strategies to circumvent host innate immunity. Some viruses use the host innate response as a vital part of the replication cycle, for example by taking advantage of innate responses the number of cell surface viral receptors may increase or use of an expanded endoplasmic reticulum for virus assembly.


Management of COVID‐19 in hemodialysis patients: The Genoa experience


title: Overview of the marmoset as a model in nonclinical development of pharmaceutical products

text: Abstract Callithrix jacchus (common marmoset) is one of the more primitive non-human primate species and is used widely in fundamental biology, pharmacology and toxicology studies. Marmosets breed well in captivity with good reproductive efficiencies and their sexual maturity is reached within 18months of age allowing for rapid expansion of colonies and early availability of sexually mature animals permitting an earlier assessment of product candidates in the adult. Their relatively small size allows a reduction in material requirements leading to a reduction in development time and cost. Fewer animals are also required due to their ability to be used in both pharmacology and toxicology (nonclinical) studies. These factors, alongside a better understanding of their optimal nutrient and welfare requirements over recent years, facilitate the generation of a more cohesive and robust dataset. With the growth of biotechnology-derived pharmaceuticals, non-human primate use has, by necessity, also increased; nevertheless, there is also a growing public call for minimizing their use. Utilizing, the more primitive marmoset species may provide the optimal compromise and once the scientific rationale has been carefully considered and their use justified, there are several advantages to using the marmoset as a model in nonclinical development of pharmaceutical products.


title: Point‐of‐care ultrasound in respiratory and critical care: consolidation and expansion of imaging skills

text: We thank Drs Sikachi and Agrawal [1] for their response to our article [2] and wholeheartedly agree that point of care ultrasound imaging has a valuable role to play across a range of organ systems and disease presentations [3], including those of relevance in COVID-19 disease.


title: Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9

text: Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9). Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi). All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.


title: Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

text: Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.


title: Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

text: Normal epithelial and endothelial renewal and healing after bacterial and viral challenges are essential for homeostasis along the intestine and the blood and lymphatic vessels. We thus investigated whether and how virus affects migration of human epithelial cells and specifically how the nucleocapsid protein (N) modulates the cellular proteome and interactome using human Caco-2 cells in a wound-healing assay with Hazara virus as a model. Here, Hazara virus blocked cell migration in a dose- and time-dependent manner, disrupted the actin cytoskeleton and specifically reduced the expression of the IQ-motif-containing GTPase-activating protein 1 (IQGAP1) and water channel aquaporin 6 (AQP6) that regulate cytoskeletal organization, water homeostasis and vesicle communication. Moreover, in the Caco-2 cell proteome, we identified several distinct groups of molecules associating with N upon Hazara virus infection, being involved in the ensemble of important cellular processes, e.g., chaperone activity, metabolism, cellular defense against infections, cell morphology, and migration. These events do not only facilitate the virus life cycle, but they are also crucial for membrane and cytoskeleton dynamics, cellular self-renewal and wound healing, being so essential for body integrity and homeostasis.


title: Depletion of RIPK1 in hepatocytes exacerbates liver damage in fulminant viral hepatitis

text: The protein kinase RIPK1 plays a crucial role at the crossroad of stress-induced signaling pathways that affects cell’s decision to live or die. The present study aimed to define the role of RIPK1 in hepatocytes during fulminant viral hepatitis, a worldwide syndrome mainly observed in hepatitis B virus (HBV) infected patients. Mice deficient for RIPK1, specifically in liver parenchymal cells (Ripk1(LPC-KO)) and their wild-type littermates (Ripk1(fl/fl)), were challenged by either the murine hepatitis virus type 3 (MHV3) or poly I:C, a synthetic analog of double-stranded RNA mimicking viral pathogen-associated molecular pattern. Ripk1(LPC-KO) mice developed more severe symptoms at early stage of the MHV3-induced fulminant hepatitis. Similarly, administration of poly I:C only triggered increase of systemic transaminases in Ripk1(LPC-KO) mice, reflecting liver damage through induced apoptosis as illustrated by cleaved-caspase 3 labeling of liver tissue sections. Neutralization of TNF-α or prior depletion of macrophages were able to prevent the appearance of apoptosis of hepatocytes in poly I:C-challenged Ripk1(LPC-KO) mice. Moreover, poly I:C never induced direct hepatocyte death in primary culture whatever the murine genotype, while it always stimulated an anti-viral response. Our investigations demonstrated that RIPK1 protects hepatocytes from TNF-α secreted from macrophages during viral induced fulminant hepatitis. These data emphasize the potential worsening risks of an HBV infection in people with polymorphism or homozygous amorphic mutations already described for the RIPK1 gene.


KEY HIGHLIGHTS from the Canadian Thoracic Society’s Position Statement on Optimizing the Management of Sleep Disordered Breathing during the COVID-19 Pandemic.


Response to the Ebola virus disease outbreak in the Democratic Republic of the Congo


title: Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics)

text: The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic.


title: The Cruise Industry and the COVID-19 Outbreak

text: Abstract The movement of cruise ships has the potential to be a major trigger of coronavirus disease (COVID-19) outbreaks. In Australia, the cruise ship Ruby Princess became the largest COVID-19 epicenter. When the Ruby Princess arrived at the Port of Sydney in New South Wales on March 19, 2020, approximately 2,700 passengers disembarked. By March 24, about 130 had tested positive for COVID-19, and by March 27, the number had increased to 162. The purpose of this study is to analyze the relationship between the cruise industry and the COVID-19 outbreak. We take two perspectives: the first analysis focuses on the relationship between the estimated number of cruise passengers landing and the number of COVID-19 cases. We tracked the movement of all ocean cruise ships around the world using automatic identification system data from January to March 2020. We found that countries with arrival and departure ports and with ports that continued to accept cruise ships until March have a higher COVID-19 infection rate than countries that did not. The second analysis focuses on the characteristics of cruise ships infected with COVID-19. For this purpose, we utilize the list named “Cruise ships affected by COVID-19” released by the Centers for Disease Control and Prevention. As a result, cruise ships infected with COVID-19 were large in size and operated regular cruises that sailed from the same port of arrival and departure to the same ports of call on a weekly basis.


title: Development of Animal Models Against Emerging Coronaviruses: From SARS to MERS coronavirus

text: Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.


title: Global health security and the International Health Regulations

text: Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR) of the World Health Organization (WHO). The current HR(2005) contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever) required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005) call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO), global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1) pandemic of 2009-2010.


siRNA could be a potential therapy for COVID-19


title: National inventory of emergency departments in Singapore

text: BACKGROUND: Emergency departments (EDs) are the basic units of emergency care. We performed a national inventory of all Singapore EDs and describe their characteristics and capabilities. METHODS: Singapore EDs accessible to the general public 24/7 were surveyed using the National ED Inventories instrument ( http://www.emnet-nedi.org). ED staff members were asked about ED characteristics with reference to calendar year 2007. RESULTS: Fourteen EDs participated (100% response). All EDs were located in hospitals, and most (92%) were independent departments. One was a psychiatric ED; the rest were general EDs. Among general EDs, all had a contiguous layout, with medical and surgical care provided in one area. All but two EDs saw both adults and children; one ED was adult-only, and the other saw only children. Six were in the public sector and seven in private health-care institutions, with public EDs seeing the majority (78%) of ED patients. Each private ED had an annual patient census of <30,000. These EDs received 2% of ambulances and had an inpatient admission rate of 7%. Each public ED had an annual census of >60,000. They received 98% of ambulances and had an inpatient admission rate of 30%. Two public EDs reported being overcapacity; no private EDs did. For both public and private EDs, availability of consultant resources in EDs was high, while technological resources varied. CONCLUSION: Characteristics and capabilities of Singapore EDs varied and were largely dependent on whether they are in public or private hospitals. This initial inventory establishes a benchmark to further monitor the development of emergency care in Singapore.


Dental student creates coronavirus e-book for children.


Time To Expand Access and Utilization of Home Dialysis: Lessons From the COVID-19 Pandemic


title: Towards construction of viral vectors based on avian coronavirus infectious bronchitis virus for gene delivery and vaccine development

text: Abstract Manipulation of the coronavirus genome to accommodate and express foreign genes is an attractive approach for gene delivery and vaccine development. By using an infectious cloning system developed recently for the avian coronavirus infectious bronchitis virus (IBV), the enhanced green fluorescent protein (EGFP) gene, the firefly luciferase gene and several host and viral genes (eIF3f, SARS ORF6, Dengue virus 1 core protein gene) were inserted into various positions of the IBV genome, and the effects on gene expression, virus recovery, and stability in cell culture were studied. Selected viruses were also inoculated into chicken embryos for studies of foreign gene expression at different tissue level. The results demonstrated the stability of recombinant viruses depends on the intrinsic properties of the foreign gene itself as well as the position at which the foreign genes were inserted. For unstable viruses, the loss of expression of the inserted genes was found to result from a large deletion of the inserted gene and even IBV backbone sequences. This represents a promising system for development of coronavirus-based gene delivery vectors and vaccines against coronavirus and other viral infections in chicken.


title: Biogeopolitics of COVID‐19: Asylum‐Related Migrants at the European Union Borderlands

text: In biogeopolitics, the key state stakeholders develop and aim to accomplish their geopolitical goals by (mis)management and biopolitical governance of vulnerable population. In this paper, this population refers to asylum‐related migrants who use or aim to use an asylum request as their entry mechanism to the European Union. This paper explores the emergence of biogeopolitics at the EU borderland between Turkey and Greece during the COVID‐19 pandemic in 2020. Statistics about irregular migration from Turkey to Greece, field observations in Lesvos (Greece) as well as media and social media discussions about COVID‐19 in Lesvos are analysed. In the biogeopolitics of COVID‐19, the governance and (mis)management of asylum‐related migrants include policies and practices to let these migrants to live or die, including regulating illegal border‐crossings, everyday living conditions at the reception centres, and actions regarding the pandemic. The COVID‐19 pandemic was used as an additional tool to foster biogeopolitics.


title: ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Chinese people in December 2019 and has currently spread worldwide causing the COVID-19 pandemic with more than 150,000 deaths. In order for a SARS-CoV like virus circulating in wild life for a very long time to infect the index case-patient, a number of conditions must be met, foremost among which is the encounter with humans and the presence in homo sapiens of a cellular receptor allowing the virus to bind. Recently it was shown that the SARS-CoV-2 spike protein, binds to the human angiotensin I converting enzyme 2 (ACE2). This molecule is a peptidase expressed at the surface of lung epithelial cells and other tissues, that regulates the renin-angiotensin-aldosterone system. Humans are not equal with respect to the expression levels of the cellular ACE2. Moreover, ACE2 polymorphisms were recently described in human populations. Here we review the most recent evidence that ACE2 expression and/or polymorphism could influence both the susceptibility of people to SARS-CoV-2 infection and the outcome of the COVID-19 disease. Further exploration of the relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.


title: Human rhinoviruses: The cold wars resume

text: Abstract Background Human rhinoviruses (HRVs) are the most common cause of viral illness worldwide but today, less than half the strains have been sequenced and only a handful examined structurally. This viral super-group, known for decades, has still to face the full force of a molecular biology onslaught. However, newly identified viruses (NIVs) including human metapneumovirus and bocavirus and emergent viruses including SARS-CoV have already been exhaustively scrutinized. The clinical impact of most respiratory NIVs is attributable to one or two major strains but there are 100+ distinct HRVs and, because we have never sought them independently, we must arbitrarily divide the literature's clinical impact findings among them. Early findings from infection studies and use of inefficient detection methods have shaped the way we think of ‘common cold’ viruses today. Objectives To review past HRV-related studies in order to put recent HRV discoveries into context. Results HRV infections result in undue antibiotic prescriptions, sizable healthcare-related expenditure and exacerbation of expiratory wheezing associated with hospital admission. Conclusion The finding of many divergent and previously unrecognized HRV strains has drawn attention and resources back to the most widespread and frequent infectious agent of humans; providing us the chance to seize the advantage in a decades-long cold war.


Response to “COVID-19: room for treating T cell exhaustion?”


title: Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function

text: Angiotensin-converting enzyme 2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the COOH-terminus of its substrates. Because ACE2 efficiently hydrolyzes the potent vasoconstrictor angiotensin II to angiotensin (1–7), this has changed our overall perspective about the classical view of the renin angiotensin system in the regulation of hypertension and heart and renal function, because it represents the first example of a feedforward mechanism directed toward mitigation of the actions of angiotensin II. This paper reviews the new data regarding the biochemistry of angiotensin-(1–7)-forming enzymes and discusses key findings such as the elucidation of the regulatory mechanisms participating in the expression of ACE2 and angiotensin-(1–7) in the control of the circulation.


title: Internet blogs as a tourism marketing medium: A case study

text: Abstract This study explores a 2003 Yahoo Anniversary Website–I left my heart in Aegean Sea–built by Justin, a Taiwanese engineer. Justin returns from the romantic Aegean Sea and puts 124 photographs he took onto a website to share with his friends. Unexpectedly, the website becomes a hit and the address achieves wide distribution via various chain e-mails. The site helps to promote tourism to Greece, a destination relatively unknown to most Taiwanese. This investigation explores why the site appeals to so many visitors, impresses them, and even draws them to plan travel to Greece. The article describes the effect of the website by analyzing messages left on the site. The AIDA model is useful for classifying holistic messages. The data demonstrate that the website generates desire and action in over 45% of its readers. These individuals either announce plans to visit Greece immediately or at some time in the foreseeable future. The website thus significantly influences browsers and indirectly promotes Greek tourism. Then, this article describes the key success factors of this popular website. Finally, the article presents suggestions and implications for the tourism industry and for nations seeking to promote tourism.


title: On the Use of Human Mobility Proxies for Modeling Epidemics

text: Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.


title: Prevalence of Salmonella, Yersinia and Campylobacter spp. in Feral Raccoons (Procyon lotor) and Masked Palm Civets (Paguma larvata) in Japan

text: To estimate the public and animal health risk that alien species pose, the prevalence of Salmonella, Yersinia, and Campylobacter spp. in feral raccoons (Procyon lotor, n = 459) and masked palm civets (Paguma larvata, n = 153), which are abundant alien species in Japan, was investigated in urban and suburban areas of Japan. Salmonella enterica was detected from 29 samples [26 raccoons, 5.7%, 95% confidence interval (CI) 7.8–3.5%; three masked palm civets, 2.0%, 95% CI 4.2–0%]. Many of the isolates belonged to serovars that are commonly isolated from human gastroenteritis patients (e.g. S. Infantis, S. Typhimurium, and S. Thompson). The antimicrobial susceptibility test showed that 26.9 % of the isolates from raccoons were resistant to at least one antimicrobial agent, whereas none of the isolates from masked palm civets were resistant. Yersinia sp. was detected from 193 samples (177 raccoons, 38.6%, 95% CI 43.0–34.1%; 16 masked palm civets, 10.5%, 95% CI 15.3–5.6%). All virulent Yersinia strains belonged to Yersinia pseudotuberculosis, which was isolated from seven (1.5%, 95% CI 2.6–0.4%) raccoons and six (3.9%, 95% CI 7.0–0.8%) masked palm civets. According to the detection of virulence factors, all the Y. pseudotuberculosis isolates belonged to the Far Eastern systemic pathogenicity type. Campylobacter spp. was detected from 17 samples (six raccoons, 1.3%, 95% CI 2.3–0.3%; 11 masked palm civets, 7.2%, 95% CI 11.3–3.1%). Among these, three isolates from raccoons were identified as C. jejuni. These results showed that these pathogens can be transmitted by human activities, other wild animals, and the environment to feral raccoons and masked palm civets, and vice versa. As these animals have omnivorous behaviour and a wide range of habitats, they can play an important role in the transmission of the enteric pathogens.


title: Autophagy: molecular mechanisms, physiological functions and relevance in human pathology

text: Autophagy is a degradative mechanism mainly involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. Over the last years, yeast genetic screens have considerably increased our knowledge about the molecular mechanisms of autophagy, and a number of genes involved in fundamental steps of the autophagic pathway have been identified. Most of these autophagy genes are present in higher eukaryotes indicating that this process has been evolutionarily conserved. In yeast, autophagy is mainly involved in adaptation to starvation, but in multicellular organisms this route has emerged as a multifunctional pathway involved in a variety of additional processes such as programmed cell death, removal of damaged organelles and development of different tissue-specific functions. Furthermore, autophagy is associated with a growing number of pathological conditions, including cancer, myopathies and neurodegenerative disorders. The physiological and pathological roles of autophagy, as well as the molecular mechanisms underlying this multifunctional pathway, are discussed in this review.


Increased Flare of Acne Caused by Long‐Time Mask Wearing During COVID‐19 Pandemic among General Population


title: Propagation of Human Embryonic Stem Cells on Human Amniotic Fluid Cells as Feeder Cells in Xeno-Free Culture Conditions

text: Human embryonic stem cells (hESCs) have been routinely cultured on mouse embryonic fibroblast feederlayers with a medium containing animal materials. For clinical application of hESCs, animal-derived products from the animal feeder cells, animal substrates such as gelatin or Matrigel and animal serum are strictly to be eliminated in the culture system. In this study, we performed that SNUhES32 and H1 were cultured on human amniotic fluid cells (hAFCs) with KOSR XenoFree and a humanized substrate. All of hESCs were relatively well propagated on hAFCs feeders with xeno-free conditions and they expressed pluripotent stem cell markers, alkaline phosphatase, SSEA-4, TRA1-60, TRA1-81, Oct-4, and Nanog like hESCs cultured on STO or human foreskin fibroblast feeders. In addition, we observed the expression of nonhuman N-glycolylneuraminic acid (Neu5GC) molecules by flow cytometry, which was xenotransplantation components of contamination in hESCs cultured on animal feeder conditions, was not detected in this xeno-free condition. In conclusion, SNUhES32 and H1 could be maintained on hAFCs for humanized culture conditions, therefore, we suggested that new xenofree conditions for clinical grade hESCs culture will be useful data in future clinical studies.


title: Facile cleavage of C–C bond: conversion of pyrane derivative to 1,3-oxazin derivative

text: Abstract A cascade reaction that involves a unique C–C bond cleavage has been discovered. This protocol affords an unusual and facile method for the synthesis of 1,3-oxazin derivatives under mild conditions.


title: Effects of allochthonous inputs in the control of infectious disease of prey

text: Abstract Allochthonous inputs are important sources of productivity in many food webs and their influences on food chain model demand further investigations. In this paper, assuming the existence of allochthonous inputs for intermediate predator, a food chain model is formulated with disease in the prey. The stability and persistence conditions of the equilibrium points are determined. Extinction criterion for infected prey population is obtained. It is shown that suitable amount of allochthonous inputs to intermediate predator can control infectious disease of prey population, provided initial intermediate predator population is above a critical value. This critical intermediate population size increases monotonically with the increase of infection rate. It is also shown that control of infectious disease of prey is possible in some cases of seasonally varying contact rate. Dynamical behaviours of the model are investigated numerically through one and two parameter bifurcation analysis using MATCONT 2.5.1 package. The occurrence of Hopf and its continuation curves are noted with the variation of infection rate and allochthonous food availability. The continuation curves of limit point cycle and Neimark Sacker bifurcation are drawn by varying the rate of infection and allochthonous inputs. This study introduces a novel natural non-toxic method for controlling infectious disease of prey in a food chain model.


title: Activity-based protein profiling of host–virus interactions

text: Virologists have benefited from large-scale profiling methods to discover new host–virus interactions and to learn about the mechanisms of pathogenesis. One such technique, referred to as activity-based protein profiling (ABPP), uses active site-directed probes to monitor the functional state of enzymes, taking into account post-translational interactions and modifications. ABPP gives insight into the catalytic activity of enzyme families that does not necessarily correlate with protein abundance. ABPP has been used to investigate several viruses and their interactions with their hosts. Differential enzymatic activity induced by viruses has been monitored using ABPP. In this review, we present recent advances and trends involving the use of ABPP methods in understanding host–virus interactions and in identifying novel targets for diagnostic and therapeutic applications.


title: Lamprey PHB2 maintains mitochondrial stability by tanslocation to the mitochondria under oxidative stress

text: Before we have reported lamprey PHB2 could enhance the cellular oxidative-stressed tolerance, here the aim was to explore its mechanisms. We used flow cytometry analysis to identify a Lampetra morii homologue of PHB2 (Lm-PHB2) that could significantly decrease the levels of ROS generation in HEK293T cells. According to confocal microscopy observations, Lm-PHB2 contributed to maintain the mitochondrial morphology of HEK293T cells, and then both cellular nuclear location and translocation from the nucleus to mitochondria of Lm-PHB2 were also examined in HEK293T cells under oxidative stress. We also examined the expressions and locations of various Lm-PHB2 deletion mutants and the amino acid mutant by confocal microscopy and the results showed that the translocation of Lm-PHB2 into mitochondria was dependent on the Lm-PHB2(1-50aa) region and the 17th, 48th and 57th three arginines (R) of N-terminal were very critical. In addition, the analyses of QRT-PCR and Western blot demonstrated that Lm-PHB2 increased the expression levels of OPA1 and HAX1 in HEK293T cells treated with H(2)O(2). The analyses of immunofluorescence and immunoprecipitation showed that Lm-PHB2 could interact with OPA1 and HAX1, respectively. The above mentioned results indicate that Lm-PHB2 could assist OPA1 and HAX1 to maintain mitochondrial morphology and decrease ROS levels by the translocation from the nucleus to mitochondria under oxidative stress.


title: Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs

text: BACKGROUND: Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. RESULTS: In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. CONCLUSION: The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.


title: Prevalence of hospital infection and antibiotic use at a University Medical Center in Hong Kong

text: Summary Hospital infection prevalence surveys were performed in our 1400-bed University medical centre in Hong Kong from 1985 to 1988. We investigated the rates of four major hospital-acquired infections (HAIs) (pneumonia, symptomatic urinary tract infection, surgical site infection and laboratory-confirmed bloodstream infection) in order to identify current distribution and any changes after 15 years. A one-day point prevalence study was performed on 7 September 2005. All inpatients were surveyed for HAIs, community-acquired infections (CAIs), risk factors, pathogenic isolates and antibiotics prescribed. Infections were diagnosed according to Centers for Disease Control and Prevention (CDC) criteria. In total, 1021 patients were surveyed; of these, 41 had 42 HAIs (4% prevalence) and 389 (38%) were receiving antibiotics. The commonest HAI was pneumonia (1.4%) followed by bloodstream infection (0.9%) and symptomatic urinary tract infection (0.8%). The prevalence of postoperative surgical site infection was 5.6%. The nosocomial prevalence rate was highest in the Intensive Care Unit, followed by the Pediatric and Neonatal Intensive Care Units, Children's Cancer Centre/Bone Marrow Transplant Unit and Orthopaedics with Traumatology. Meticillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were the commonest pathogens. The rates are significantly lower than previously and reflect the increased resources for infection control made available following the outbreak of severe acute respiratory syndrome (SARS).


title: Practice recommendations for risk-adapted head and neck cancer radiotherapy during the COVID-19 pandemic: an ASTRO-ESTRO consensus statement

text: Abstract Introduction Due to the unprecedented disruption of health care services by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC), in a time of heightened risk for patients and staff, and of limited resources. Methods A panel of international experts from ASTRO, ESTRO and select Asia-Pacific countries completed a modified rapid Delphi process. Questions and topics were presented to the group, and subsequent questions developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios: early (risk mitigation) and late (severely reduced radiotherapy resources) were evaluated. The panel developed treatment recommendations for five HNC cases. Results In total, 29/31 (94%) of those invited accepted, and after a replacement 30/30 completed all three surveys (100% response rate). There was agreement or strong agreement across a number of practice areas including: treatment prioritisation, whether to delay initiation or interrupt radiotherapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.