title: Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

text: Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2,′5′-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother’s peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.


title: To Do or Not to Do?—A Review of Cancer Surgery Triage Guidelines in COVID-19 Pandemic

text: COVID-19 pandemic has emerged as a global health emergency involving more than 200 countries so far. The number of affected population is on rising, so is the mortality. This crisis has overwhelmed the healthcare infrastructures in many affected countries. Due to overall rising cancer incidence and specific concerns, a cohort of cancer patients forms a distinct subset of the population in whom a correct and timely treatment has a huge impact on the outcome. During this period, oncology care is definitely affected owing to many factors like lockdowns, reduced beds and deferral of elective cases to halt the spread of the pandemic. Surgery remains the best line of defence in many solid organ tumours especially in early stage and is potentially curative. China, the source of this pandemic, has taken more than 3 months to enter the post transitional phase of this pandemic. Deferring cancer surgeries for this long period may have a direct impact on the long-term outcomes of cancer patients. Many surgical oncology associations across the globe have come up with triage guidelines for surgical care of cancer patients; however, these are based on expert opinion rather than actual data. Herein, we intend to review these guidelines with respect to the risk of disease progression in cancer patients. In the absence of actual data on cancer surgery care during this pandemic, clinical decisions should be based on careful consideration of disease-related and patient-related factors. While some of the cancer surgeries can be safely delayed for some time, how long we can delay surgeries safely cannot be answered/ explained by any means. Thorough evaluation and discussion by an expert and experienced multidisciplinary team appears to be the most effective way forward.


title: Development of rapid immunochromatographic strip test for the detection of porcine epidemic diarrhoea virus

text: Porcine epidemic diarrhoea virus (PEDV) causes acute and severe watery diarrhoea and dehydration, as well as 50–100 per cent mortality in piglets. For the PEDV diagnosis, a rapid test kit that is specific and sensitive to PEDV is critical to monitor this disease at pig farms. The present study aimed to develop an immunochromatographic assay (ICA) strip test for detecting PEDV in faecal swabs. The newly developed diagnostic test showed a detection limit of 10(4.0) TCID(50)/ml of PEDV. Using faecal swab samples, the relative sensitivity and specificity of the ICA kit were 95.0 per cent and 98.6 per cent, respectively, compared with those of real-time RT-PCR. In samples from piglets experimentally infected with PEDV, the results showed 100 per cent agreement with those found by real-time RT-PCR. Our developed test strip will be useful for rapid diagnosis and can be used for epidemiological surveillance of PEDV infection.


title: Networked disease: emerging infections in the global city S Harris Ali Roger

text: Unknown


title: Changing circulation rate of human metapneumovirus strains and types among hospitalized pediatric patients during three consecutive winter-spring seasons

text: From 2001 through 2004, 808 pediatric patients admitted to hospital because of acute respiratory infections were examined for presence of respiratory viruses by either direct fluorescent staining using monoclonal antibodies or RT-PCR during three consecutive winter-spring seasons. On the whole, 336 (42%) patients were detected as positive for one or more respiratory viruses. The most widely circulating virus was human respiratory syncytial virus (hRSV) infecting 50% of positive patients, followed by human metapneumovirus (hMPV) found in 13% of patients, and then by influenza virus type A, human parainfluenzaviruses and coinfections. Significant variations in the circulation rate of hRSV, hMPV and influenzavirus type A were observed during the individual seasons. In addition, the circulation rates of the different types of hMPV changed yearly. In 2001–2002 and 2002–2003 hMPV circulated at a significant lower proportion than hRSV, while in 2003–2004 the circulation rates of the two viruses were closer. In conclusion, the 4 hMPV subtypes circulated yearly in Northern Italy flanking hRSV as major respiratory pathogens in the infantile patient population.


title: Coronavirus disease (COVID‐19): Characteristics in children and considerations for dentists providing their care

text: The emergence of the novel virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused a global pandemic called coronavirus disease (COVID‐19) and has become one of the most significant challenges to the healthcare profession. Dental practices are focal points for cross‐infection, and care must be taken to minimise the risk of infection to, from, or between dental care professionals and patients. The COVID‐19 epidemiological and clinical characteristics are still being collated but children's symptoms seem to be milder than those that adults experience. It is unknown whether certain groups, for example children with comorbidities, might be at a higher risk of more severe illness. Emerging data on disease spread in children, affected by COVID‐19, have not been presented in detail. The purpose of this article was to report current data on the paediatric population affected with COVID‐19 and highlight considerations for dentists providing care for children during this pandemic. All members of the dental team have a professional responsibility to keep themselves informed of current guidance and be vigilant in updating themselves as recommendations are changing so quickly.


Immunology: Are complement lysis and lymphocytotoxicity analogous?


title: Mitochondrial Functions in Infection and Immunity

text: Mitochondria have a central role in regulating a range of cellular activities and host responses upon bacterial infection. Multiple pathogens affect mitochondria dynamics and functions to influence their intracellular survival or evade host immunity. On the other side, major host responses elicited against infections are directly dependent on mitochondrial functions, thus placing mitochondria centrally in maintaining homeostasis upon infection. In this review, we summarize how different bacteria and viruses impact morphological and functional changes in host mitochondria and how this manipulation can influence microbial pathogenesis as well as the host cell metabolism and immune responses.


Early experiences of SARS-CoV2 infection in severe asthmatics receiving biologic therapy


title: Entity Perception of Two-Step-Matching Framework for Public Opinions

text: Abstract Entity perception of ambiguous user comments is a critical problem of target identification for huge amount of public opinions. In this paper, a Two-Step-Matching method is proposed to identify the precise target entity from multiple entities mentioned. Firstly, potential entities are extracted by BiLSTM-CRF model and characteristic words by TF-IDF model from public comments. Secondly, the first matching is implemented between potential entities and an official business directory by Jaro-Winkler distance algorithm. Then, in order to find the precise one, an industry-characteristic dictionary is developed into the second matching process. The precise entity is identified according to the count of characteristic words matching to industry-characteristic dictionary. In addition, associated rate (global indicator) and accuracy rate (sample indicator) are defined for evaluation of matching accuracy. The results for three data sets of public opinions about major public health events show that the highest associated rate and accuracy rate arrive at 0.93 and 0.95, averagely enhanced by 32% and 30% above the case of using the first matching process alone. This framework provides the method to find the true target entity of really wanted expression from public opinions.


title: Murine coronavirus neuropathogenesis: determinants of virulence

text: Murine coronavirus, mouse hepatitis virus (MHV), causes various diseases depending on the strain and route of inoculation. Both the JHM and A59 strains, when inoculated intracranially or intranasally, are neurovirulent. Comparison of the highly virulent JHM isolate, JHM.SD, with less virulent JHM isolates and with A59 has been used to determine the mechanisms and genes responsible for high neuropathogenicity of MHV. The focus of this review is on the contributions of viral spread, replication and innate and adaptive immunity to MHV neuropathogenesis. JHM.SD spreads more quickly among neurons than less neurovirulent MHVs, and is able to spread in the absence of the canonical MHV receptor, CEACAM1a. The observation that JHM.SD infects more cells and expresses more antigen, but produces less infectious virus per cell than A59 implies that efficient replication is not always a correlate of high neurovirulence. This is likely due to the unstable nature of the JHM.SD spike protein (S). JHM.SD induces a generally protective innate immune response; however, the strong neutrophil response may be more pathogenic than protective. In addition JHM.SD induces only a minimal T cell response, while the strong T cell response and the concomitant IFNγ induced by the less neurovirulent A59 is protective. Differences in the S and nucleocapsid (N) proteins between A59 and JHM.SD contribute to JHM.SD neuropathogenicity. The hemmagglutinin-esterase (HE) protein may enhance neuropathogenicity of some MHV isolates, but is unlikely a major contributor to the high neuroviruence of JHM.SD. Further data suggests that neither the internal (I) protein, nor nonstructural proteins ns4, and ns2 are significant contributors to neurovirulence.


Pandémie au virus SARS-CoV-2 en France: l’histoire d’une adaptation hors normes des soignants


title: Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases

text: BACKGROUND: The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs). METHODOLOGY/PRINCIPAL FINDINGS: The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like) could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA). Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2) of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or other virulent infectious diseases.


title: Transmission dynamics of 2019 novel coronavirus (2019-nCoV)

text: Background Since December 29, 2019, pneumonia infection with 2019-nCoV has rapidly spread out from Wuhan, Hubei Province, China to most others provinces and other counties. However, the transmission dynamics of 2019-nCoV remain unclear. Methods Data of confirmed 2019-nCoV cases before January 23, 2020 were collected from medical records, epidemiological investigations or official websites. Data of severe acute respiratory syndrome (SARS) cases in Guangdong Province during 2002-2003 were obtained from Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Exponential Growth (EG) and maximum likelihood estimation (ML) were applied to estimate the reproductive number (R) of 2019-nCoV and SARS. Findings As of January 23, 2020, a total of 830 confirmed 2019-nCoV cases were identified across China, and 9 cases were reported overseas. The average incubation duration of 2019-nCoV infection was 4.8days. The average period from onset of symptoms to isolation of 2019-nCoV and SARS cases were 2.9 and 4.2 days, respectively. The R values of 2019-nCoV were 2.90 (95%CI: 2.32-3.63) and 2.92 (95%CI: 2.28-3.67) estimated using EG and ML respectively, while the corresponding R values of SARS-CoV were 1.77 (95%CI: 1.37-2.27) and 1.85 (95%CI: 1.32-2.49). We observe a decreasing trend of the period from onset to isolation and R values of both 2019-nCoV and SARS-CoV. Interpretation The 2019-nCoV may have a higher pandemic risk than SARS broken out in 2003. The implemented public-health efforts have significantly decreased the pandemic risk of 2019-nCoV. However, more rigorous control and prevention strategies and measures to contain its further spread. Funding National Key Research and Development Program of China, Science and Technology Program of Guangdong Province, and Guangzhou Science and technology Plan Project.


title: Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis

text: A novel 5‐membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein‐processing α‐glucosidase with a K(i) value of 53 nm. This compound was further derivatized to antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN‐2), human SARS coronavirus, and human β‐hexosaminidase (K(i) =2.6 nm), a new target for the development of osteoarthritis therapeutics.


title: An adenoviral vector-based mucosal vaccine is effective in protection against botulism

text: A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a mucosal vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of H(C)50-specific IgG, IgG1 and IgG2a in sera and IgA in mucosal secretions as early as 2 weeks after vaccination. The antigen-specific serum antibodies were maintained at a high level at least until the 27th week. Immune sera showed high potency in neutralizing BoNT/C as indicated by in vitro toxin neutralization assay. The mice receiving single dose of 2 × 10(7) p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 10(4) × MLD(50) of BoNT/C. The protective immunity showed vaccine dose dependence from 10(5) to 2 × 10(7) p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 × 10(7) p.f.u. adenoviral vector could be protected against 100 × MLD(50) 27 weeks after vaccination. Animals with preexisting immunity to adenovirus could also be vaccinated intranasally and protected against lethal challenge with BoNT/C. These results suggest that the adenoviral vector is a highly effective gene-based mucosal vaccine against botulism.


title: Correlation of rhinovirus load in the respiratory tract and clinical symptoms in hospitalized immunocompetent and immunocompromised patients

text: While human rhinoviruses (HRVs) are well accepted as a major cause of common cold syndromes (rhinitis), their role in the etiology of lower respiratory tract infections is still controversial, and their detection in asymptomatic patients is relatively common. The HRV pathogenic role in four groups of hospitalized patients (pediatric immunocompetent and immunocompromised patients, and adult immunocompetent and immunocompromised patients) was investigated by quantifying HRV load in nasopharyngeal aspirates or bronchoalveolar lavage samples by real‐time reverse transcription PCR (RT‐PCR). Real‐time RT‐PCR was performed in duplicate on all respiratory samples resulting positive by qualitative RT‐PCR. In addition, molecular typing allowed detection of all known HRV species (A, B, and C). In immunocompetent pediatric patients HRVs were mostly associated with lower respiratory tract infections (in the absence of other viral agents) and wheezing, when viral load was ≥10(6) RNA copies/ml. In young immunocompromised patients (stem cell transplantation recipients), an inverse correlation between HRV persistence over time and time at which the infection occurred after transplantation was observed, whereas in adult immunocompromised patients (lung transplant recipients) HRVs could be detected at a medium–low level (<10(5) RNA copies/ml) in bronchoalveolar lavage samples taken routinely from asymptomatic patients. In conclusion, when detected at high viral load, HRVs may cause severe upper and lower respiratory tract infections, whereas when detected at a medium–low viral load, an event more frequent in immunocompromised subjects, they may represent only bystander viruses. J. Med. Virol. 81:1498–1507, 2009. © 2009 Wiley‐Liss, Inc.


title: Tourism jobs in demand: Where the best contracts and high salaries go at online offers

text: It has been suggested that the tourism sector is one in which temporary and low-skilled jobs abound. The aim of this study is to analyze the educational and experience requirements associated with job offers in tourism and their corresponding contracts and salaries. Nine thousand job advertisements were analyzed from one of the biggest employment websites in Spain. Online job offers allow a profile of employers' preferences to be drawn up in terms of occupations, educational levels and required experience, as well as the terms of contracts and salaries offered. Internal heterogeneity in the tourism sector arising from the coexistence of different functions and skills is highlighted. Our analysis shows that the occupation crucially conditions salary differences and contract types in tourism job offers.


title: An overview of the rangelands atmosphere–hydrosphere–biosphere interaction study experiment in northeastern Asia (RAISE)

text: Summary Intensive observations, analysis and modeling within the framework of the rangelands atmosphere–hydrosphere–biosphere interaction study experiment in northeastern Asia (RAISE) project, have allowed investigations into the hydrologic cycle in the ecotone of forest-steppe, and its relation to atmosphere and ecosystem in the eastern part of Mongolia. In this region, changes in the climate have been reported and a market oriented economy was introduced recently, but their impact on the natural environment is still not well understood. In this RAISE special issue, the outcome is presented of the studies carried out by six groups within RAISE, namely: (1) Land-atmosphere interaction analysis, (2) ecosystem analysis and modeling, (3) hydrologic cycle analysis, (4) climatic modeling, (5) hydrologic modeling, and (6) integration. The results are organized in five relevant categories comprising (i) hydrologic cycle including precipitation, groundwater, and surface water, (ii) hydrologic cycle and ecosystem, (iii) surface–atmosphere interaction, (iv) effect of grazing activities on soils, plant ecosystem and surface fluxes, and (v) future prediction. Comparison with studies on rangelands in other parts of the world, and some future directions of studies still needed in this region are also summarized.


title: BrainStem Encephalitis Associated with Chandipura in Andhra Pradesh Outbreak

text: Clinical data of 104 hospitalized children during the 2003 epidemic of encephalitis in Andhra Pradesh state was retrospectively analysed to know the clinical profile and risk factors associated with mortality. Fever was the first symptom associated with altered sensorium, seizures, diarrhoea and vomiting. Evolution of illness was very rapid with high fatality (47%). Majority of deaths occurred within the first 24 h of illness due to brainstem involvement. On multiple logistic regression analysis, high-grade fever, absent oculocephalic reflex and Glasgow coma score <7 were found to be significantly contributing to the mortality. Evidence of Chandipura virus was detected in these cases as the etiological agent.


title: An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. RESULTS: PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log(10) tissue culture infective dose (TCID(50)/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log(10) TCID(50)/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log(10) TCID(50)/mL vaccinates and the negative controls. CONCLUSIONS: These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.


Biologic therapy for psoriasis during the COVID‐19 outbreak: The choice is to weigh risks and benefits


title: The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the anti-viral function of ISG15

text: ISG15 is an interferon-induced and anti-viral ubiquitin-like protein (Ubl). Herc5, the major E3 enzyme for ISG15, mediates the ISGylation of over 300 proteins in interferon-stimulated cells. In addressing this broad substrate selectivity of Herc5, we found that: 1) the range of substrates extends even further and includes many exogenously expressed foreign proteins, 2) ISG15 conjugation is restricted to newly synthesized pools of proteins, and 3) Herc5 is physically associated with polyribosomes. These results lead to a model for ISGylation in which Herc5 broadly modifies newly synthesized proteins in a co-translational manner. This represents a novel mechanism for conjugation of a Ubl and further suggests that, in the context of an interferon-stimulated cell, newly translated viral proteins may be primary targets of ISG15. Consistent with this, we demonstrate that ISGylation of human papillomavirus (HPV) L1 capsid protein has a dominant-inhibitory effect on the infectivity of HPV16 pseudoviruses.


title: Loss of Angiotensin-Converting Enzyme-2 Leads to the Late Development of Angiotensin II-Dependent Glomerulosclerosis

text: Angiotensin-converting enzyme-2 (ACE2), a membrane-bound carboxymonopeptidase highly expressed in the kidney, functions as a negative regulator of the renin-angiotensin system. Here we report early accumulation of fibrillar collagen in the glomerular mesangium of male ACE2 mutant (ACE2(−/y)) mice followed by development of glomerulosclerosis by 12 months of age whereas female ACE2 mutant (ACE2(−/−)) mice were relatively protected. Progressive kidney injury was associated with increased deposition of collagen I, collagen III and fibronectin in the glomeruli and increased urinary albumin excretion compared to age-matched control mice. These structural and functional changes in the glomeruli of male ACE2 mutant mice were prevented by treatment with the angiotensin II type-1 receptor antagonist irbesartan. Loss of ACE2 was associated with a marked increase in renal lipid peroxidation product formation and activation of mitogen-activated protein kinase and extracellular signal-regulated kinases 1 and 2 in glomeruli, events that are also prevented by angiotensin II type-1 receptor blockade. We conclude that deletion of the ACE2 gene leads to the development of angiotensin II-dependent glomerular injury in male mice. These findings have important implications for our understanding of ACE2, the renin-angiotensin system, and gender in renal injury, with ACE2 likely to be an important therapeutic target in kidney disease.


Obsessive-compulsive disorder during the COVID-19 pandemic


title: Successive Passage In Vitro Led to Lower Virulence and Higher Titer of A Variant Porcine Epidemic Diarrhea Virus

text: A highly virulent porcine epidemic diarrhea virus (PEDV) appeared in China and spread rapidly to neighbor countries, which have led to great economic losses to the pig industry. In the present study, we isolated a PEDV using Vero cells and serially propagated 100 passages. PEDV SDSX16 was characterized in vitro and in vivo. The viral titers increased to 10(7.6) TCID(50)/mL (100th) by serial passages. The spike (S) gene and the whole gene of the SDSX16 virus was fully sequenced to assess the genetic stability and relatedness to previously identified PEDV. Along with successive passage in vitro, there were 18 nucleotides (nt) deletion occurred in the spike (S) gene resulting in a deletion of six amino acids when the SDSX16 strain was passaged to the 64th generation, and this deletion was stable until the P100. However, the ORF1a/b, M, N, E, and ORF3 genes had only a few point mutations in amino acids and no deletions. According to growth kinetics experiments, the SDSX16 deletion strain significantly enhanced its replication in Vero cells since it was passaged to the 64th generation. The animal studies showed that PEDV SDSX16-P10 caused more severe diarrhea and vomiting, fecal shedding, and acute atrophic enteritis than SDSX16-P75, indicating that SDSX16-P10 is enteropathogenic in the natural host, and the pathogenicity of SDSX16 decreased with successive passage in vitro. However, SDSX16-P10 was found to cause lower levels of cytokine expression than SDSX16-P75 using real-time PCR and flow cytometry, such as IL1β, IL6, IFN-β, TNF-α, indicating that SDSX16-P10 might inhibit the expression of cytokines. Our data indicated that successive passage in vitro resulted in virulent attenuation in vivo of the PEDV variant strain SDSX16.


title: Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

text: The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in “CCR5 research” are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.


To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia‐Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska‐Polak A, Lødrup‐Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic‐Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations – A GA(2)LEN‐DARE systematic review. Allergy 2011; 66: 458–468. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type‐C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.


title: Multiple Viral Infection Detected from Influenza-Like Illness Cases in Indonesia

text: Influenza is one of the common etiologies of the upper respiratory tract infection (URTI). However, influenza virus only contributes about 20 percent of influenza-like illness patients. The aim of the study is to investigate the other viral etiologies from ILI cases in Indonesia. Of the 334 samples, 266 samples (78%) were positive at least for one virus, including 107 (42%) cases of multiple infections. Influenza virus is the most detected virus. The most frequent combination of viruses identified was adenovirus and human rhinovirus. This recent study demonstrated high detection rate of several respiratory viruses from ILI cases in Indonesia. Further studies to determine the relationship between viruses and clinical features are needed to improve respiratory disease control program.


title: Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy

text: AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.


title: Caring during COVID‐19: A gendered analysis of Australian university responses to managing remote working and caring responsibilities

text: COVID‐19 is dramatically reconfiguring paid work and care. Emerging evidence in the global media suggests that academic women with caring responsibilities are being proportionately impacted. This article fills a key knowledge gap by examining how Australian universities are supporting academics to manage remote work and caring during the COVID‐19 pandemic. We conducted a desktop analysis of public information about remote working and care from 41 Australian universities and compared them to the world’s top 10 ranked universities. Findings suggest that during the pandemic, the Australian higher education sector positions decisions about caring leave and participation in the paid labour force as ‘private’ matters in which employees (mainly women) design their own ‘solutions’ when compared with international institutional counterparts. We argue that COVID‐19 provides another context in which universities have evaded their responsibility to ensure women’s full participation in the labour force.


Respiratory Viruses in Babies: Important Insights From Down Under


title: Occurrence and Possible Roles of Polysaccharides in Fungi and their Influence on the Development of New Technologies

text: The article summarizes the roles of polysaccharides in the biology of fungi and their relationship in the development of new technologies. The comparative approach between the evolution of fungi and the chemistry of glycobiology elucidated relevant aspects about the role of polysaccharides in fungi. Also, based on the knowledge of fungal glycobiology, it was possible to address the development of new technologies, such as the production of new anti-tumor drugs, vaccines, biomaterials, and applications in the field of robotics. We conclude that polysaccharides activate pathways of apoptosis, secretion of pro-inflammatory substances, and macrophage, inducing anticancer activity. Also, the activation of the immune system, which opens the way for the production of vaccines. The development of biomaterials and parts for robotics is a promising and little-explored field. Finally, the article is multidisciplinary, with a different and integrated approach to the role of nature in the sustainable development of new technologies.


title: β-Endorphin protects mice from neurological disease induced by the murine coronavirus MHV-JHM

text: Abstract The neurotropic murine coronavirus, MHV-JHM (JHMV) causes encephalitis and paralytic-demyelinating disease in susceptible strains of mice and rats, serving as a model for human demyelinating diseases such as multiple sclerosis. In this communication, we report that a single intracerebral administration of the naturally occurring neuropeptide, β-endorphin, reduced the incidence of JHMV-induced paralytic-demyelinating disease 40–50% in C57Bl/6 mice. Protection from disease was accompanied by significantly reduced virus replication in the brain as early as 3 days post-infection and did not occur in irradiated, or immunoincompetent mice. The data suggest that β-endorphin engages immune mechanisms of host resistance to JHMV infection to protect the mice from disease.


title: Elevation of Liver Fibrosis Index FIB-4 Is Associated With Poor Clinical Outcomes in Patients With COVID-19

text: BACKGROUND: COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19. METHODS: In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35–65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. RESULTS: Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30–8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90–13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36–15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01–1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor. CONCLUSIONS: In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.


title: Addressing the Impact of the Coronavirus Disease (COVID-19) Pandemic on Hematopoietic Cell Transplantation: Learning Networks as a Means for Sharing Best Practices

text: ABSTRACT The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.


title: SARS‐CoV‐2: What can saliva tell us?

text: An epidemic pneumonia was first reported in the city of Wuhan, China, in the end of December 2019, had its aetiological agent identified as a new coronavirus (Zhu et al., 2020). The World Health Organisation (WHO) declared on 11 March 2020 that the epidemic of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic now called COVID-19.


title: Age Matters but it should not be Used to Discriminate Against the Elderly in Allocating Scarce Resources in the Context of COVID-19

text: A patient’s age serves as a very useful guide to physicians in deciding what disease manifestations to anticipate, what treatment to offer for certain conditions, and how to prepare for possible emergencies. In the context of the COVID-19 pandemic, determining treatment options on the basis of a patient’s chronological age can easily give rise to unjustified discrimination. This is of particular significance in situations where the allocation of scarce critical care resources could have a direct impact on who will live and who will die. This paper examines the fairness of recommendations contained in resource allocation guidelines in the Philippines that have implications for the way elderly patients could be treated or excluded from some forms of critical care treatment in the context of the ongoing Corona virus emergency.


From SARS to COVID‐19: the Singapore journey


title: Secondary structure and mutational analysis of the ribosomal frameshift signal of rous sarcoma virus 1 1 Edited by D. E. Draper

text: Abstract Expression of the Gag-Pol polyprotein of Rous sarcoma virus (RSV) requires a −1 ribosomal frameshifting event at the overlap region of the gag and pol open reading frames. The signal for frameshifting is composed of two essential mRNA elements; a slippery sequence (AAAUUUA) where the ribosome changes reading frame, and a stimulatory RNA structure located immediately downstream. This RNA is predicted to be a complex stem-loop but may also form an RNA pseudoknot. We have investigated the structure of the RSV frameshift signal by a combination of enzymatic and chemical structure probing and site-directed mutagenesis. The stimulatory RNA is indeed a complex stem-loop with a long stable stem and two additional stem-loops contained as substructures within the main loop region. The substructures are not however required for frameshifting. Evidence for an additional interaction between a stretch of nucleotides in the main loop and a region downstream to generate an RNA pseudoknot was obtained from an analysis of the frameshifting properties of RSV mutants translated in the rabbit reticulocyte lysate in vitro translation system. Mutations that disrupted the predicted pseudoknot-forming sequences reduced frameshifting but when the mutations were combined and should re-form the pseudoknot, frameshifting was restored to a level approaching that of the wild-type construct. It was also observed that the predicted pseudoknot-forming regions had reduced sensitivity to cleavage by the single-stranded probe imidazole. Overall, however, the structure probing data indicate that the pseudoknot interaction is weak and may form transiently. In comparison to other characterised RNA structures present at viral frameshift signals, the RSV stimulator falls into a novel group. It cannot be considered to be a simple hairpin-loop yet it is distinct from other well characterised frameshift-inducing RNA pseudoknots in that the overall contribution of the RSV pseudoknot to frameshifting is less dramatic.


title: Challenges faced by mental health providers and patients during the coronavirus 2019 pandemic due to technological barriers

text: BACKGROUND: The novel coronavirus, SARS-CoV-2, has been responsible for the devastation of hundreds of thousands of lives directly and has caused disruptions globally. Vulnerable populations, specifically those suffering from serious mental illness and homelessness, are at higher risk of contracting COVID-19 infection resulting in medical complications and psychiatric destabilization. In addition, mental health has become increasingly relevant throughout the country given the psychological distress people have been facing due to the spread of COVID-19 and the toll of a more restricted way of living. Although the healthcare industry has quickly integrated novel ways of treating patients with mental illness with technological advances, these technologies are not applicable to different populations equally. There is a clear disparity that is represented within the public county health systems, which leads to a widening gap between those who receive adequate treatment for mental illness and those who do not. AIMS: The aims of this paper were to provide a commentary on the benefits of technology-based psychiatric and psychological interventions based off experience in a public health system and based off a relevant, thorough literature review. In addition, we aim to highlight the importance of accessibility of these interventions for vulnerable populations and provide recommendations for integrating these services expeditiously. METHODS: Literature review was conducted using MEDLINE, PubMed and Google Scholar. CONCLUSIONS: Based off data collected from experience in a public health system and literature review, we conclude that although the COVID-19 pandemic has initiated significant innovation to integrate technology for psychiatric care, this innovation is not equally accessible for vulnerable populations suffering from mental health disorders. Within a public county health system, there are barriers with providing mental healthcare to vulnerable populations. These barriers, which are applicable throughout the United States, serve as a rationale for the need of innovative solutions for the integration of these services in not only emergency situations such as the COVID-19 pandemic, but also in daily non-emergent operations to sufficiently address the needs for those needing mental healthcare.


title: Human Metapneumovirus Infection in Chimpanzees, United States

text: Zoonotic disease transmission and infections are of particular concern for humans and closely related great apes. In 2009, an outbreak of human metapneumovirus infection was associated with the death of a captive chimpanzee in Chicago, Illinois, USA. Biosecurity and surveillance for this virus in captive great ape populations should be considered.


title: Membrane Fusion

text: Membrane fusion of enveloped viruses with cellular membranes is mediated by viral glycoproteins, which are activated by proteolytic cleavage and/or interaction with cellular receptors. Fusion entails extensive conformational changes of the fusion protein that initially anchors to cellular membranes thus bridging two bilayers. Further refolding into a hairpin-like structure pulls viral and cellular membranes into close proximity to permit lipid bilayer fusion. Refolding provides the energy for fusion, which follows several defined lipidic intermediate states occurring concomitantly with refolding. Although different classes of fusion proteins use different structural motifs, the principle of repositioning both membrane anchors, the transmembrane and the fusion peptide region, at the same end of an elongated hairpin structure generated by receptor binding is maintained in all known viral fusion protein structures, suggesting that they follow similar principles to achieve lipid bilayer fusion.


title: NAATP on telemedicine and a ‘disease of isolation’

text: Because of COVID‐19 social distancing, many people are unable to go to in‐person recovery support meetings, or to treatment. There's not a lot of evidence about telemedicine and substance use disorder (SUD) treatment, because telemedicine is so recent, said Chelsey Cusimano, executive administrator of the National Association of Addiction Treatment Providers (NAATP). But it is all people have now.


title: COVID-19-related prejudice towards Asian medical students: A consequence of SARS-CoV-2 fears in Poland

text: Abstract The coronavirus disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 has triggered global panic. We have conducted an anonymous online survey of Asian medical students in Poland to assess whether they experience any form of prejudice related to the ongoing pandemic. As demonstrated, the COVID-19 outbreak had triggered xenophobic reactions towards students of Asian-origin (n=85) before the first SARS-CoV-2 case was confirmed in Poland. Facing prejudice, including discrimination related to COVID-19, may add to feelings of isolation of students of Asian origin who study abroad, and affect career development, especially for students. We recommend that universities should proactively develop policies that support students, faculty, and staff affected by discriminatory behavior both during the current outbreak and in the future. However, preventing such behaviors should also be enforced by national authorities


title: Co-variance nexus between COVID-19 mortality, humidity, and air quality index in Wuhan, China: New insights from partial and multiple wavelet coherence

text: The worldwide outbreak of COVID-19 disease has caused immense damage to our health and economic and social life. This research article helps to determine the impact of climate on the lethality of this disease. Air quality index and average humidity are selected from the family of climate variables, to determine its impact on the daily new cases of COVID-19-related deaths in Wuhan, China. We have used wavelet analysis (wavelet transform coherence (WTC), partial (PWC), and multiple wavelet coherence (MWC), due to its advantages over traditional time series methods, to study the co-movement nexus between our selected data series. Findings suggest a notable coherence between air quality index, humidity, and mortality in Wuhan during a recent outbreak. Humidity is negatively related to the COVID-19-related deaths, and bad air quality leads to an increase in this mortality. These findings are important for policymakers to save precious human lives by better understanding the interaction of the environment with the COVID-19 disease.


title: Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Part 2: Potential Alternatives to the Use of Animals in Preclinical Trials

text: Dramatically rising costs in drug development are in large part because of the high failure rates in clinical phase trials. The poor correlation of animal studies to human toxicity and efficacy have led many developers to question the value of requiring animal studies in determining which drugs should enter in-human trials. Part 1 of this 2-part series examined some of the data regarding the lack of concordance between animal toxicity studies and human trials, as well as some of the potential reasons behind it. This second part of the series focuses on some alternatives to animal trials (hereafter referred to as animal research) as well as current regulatory discussions and developments regarding such alternatives.


title: APA poll finds nearly half anxious about getting COVID‐19

text: Nearly half of Americans (48%) are anxious about the possibility of getting COVID‐19, and nearly four in 10 Americans (40%) are anxious about becoming seriously ill or dying from it, according to a new national poll released by the American Psychiatric Association (APA) March 15. However, many more Americans (62%) are anxious about the possibility of family and loved ones getting the coronavirus, the APA stated.


title: Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective

text: The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp. Communicated by Ramaswamy H. Sarma


title: At the Epicentre: Hong Kong and the SARS Outbreak Christine Loh Civic

text: Unknown


title: Henipavirus Neutralising Antibodies in an Isolated Island Population of African Fruit Bats

text: Isolated islands provide valuable opportunities to study the persistence of viruses in wildlife populations, including population size thresholds such as the critical community size. The straw-coloured fruit bat, Eidolon helvum, has been identified as a reservoir for henipaviruses (serological evidence) and Lagos bat virus (LBV; virus isolation and serological evidence) in continental Africa. Here, we sampled from a remote population of E. helvum annobonensis fruit bats on Annobón island in the Gulf of Guinea to investigate whether antibodies to these viruses also exist in this isolated subspecies. Henipavirus serological analyses (Luminex multiplexed binding and inhibition assays, virus neutralisation tests and western blots) and lyssavirus serological analyses (LBV: modified Fluorescent Antibody Virus Neutralisation test, LBV and Mokola virus: lentivirus pseudovirus neutralisation assay) were undertaken on 73 and 70 samples respectively. Given the isolation of fruit bats on Annobón and their lack of connectivity with other populations, it was expected that the population size on the island would be too small to allow persistence of viruses that are thought to cause acute and immunising infections. However, the presence of antibodies against henipaviruses was detected using the Luminex binding assay and confirmed using alternative assays. Neutralising antibodies to LBV were detected in one bat using both assays. We demonstrate clear evidence for exposure of multiple individuals to henipaviruses in this remote population of E. helvum annobonensis fruit bats on Annobón island. The situation is less clear for LBV. Seroprevalences to henipaviruses and LBV in Annobón are notably different to those in E. helvum in continental locations studied using the same sampling techniques and assays. Whilst cross-sectional serological studies in wildlife populations cannot provide details on viral dynamics within populations, valuable information on the presence or absence of viruses may be obtained and utilised for informing future studies.


Editorial: A home for virology, ecology, epidemiology, and evolutionary biology


La alteración del olfato y el gusto en pacientes COVID-19. Un recurso diagnostico en atención primaria


A new Director General for WHO—an opportunity for bold and inspirational leadership


title: Gastrointestinal Disorders of Donkeys and Mules

text: A review of common gastrointestinal disorders of donkeys and mules is presented. Clinically relevant aspects of donkey behavior, anatomy, and physiology are highlighted. Diagnosis, management, and treatment of conditions affecting the gastrointestinal tract from stomach to rectum, including liver and pancreas, are discussed.


title: Attenuation of Viruses by Large-Scale Recoding of their Genomes: the Selection Is Always Biased

text: PURPOSE OF REVIEW: This review summarizes the current understanding of virus attenuation by large-scale recoding of viral genomes and discusses what would ultimately be necessary for construction of better and safer live modified virus vaccines. RECENT FINDINGS: It has been shown that codon and codon pair deoptimization are rapid and robust methods that can be used for the development of attenuated vaccine candidates. The viruses attenuated by large-scale recoding have the added value that they are extremely genetically stable. However, the exact mechanisms that lead to viral attenuation by recoding are yet to be determined. SUMMARY: While the advantages of large-scale recoding (speed, simplicity, potency, and universal applicability) have been known for more than a decade, this approach has been only inadequately explored and the attention was focused on a limited number of RNA viruses. Attenuation of viruses by large-scale recoding should be explored to combat known and future viral threats.


title: Perception and Attitude of Emergency Room Resident Physicians toward Middle East Respiratory Syndrome Outbreak

text: Introduction. Middle East respiratory syndrome (MERS) outbreaks have had a considerable negative impact on health systems in Saudi Arabia. We aimed to study the psychological impact of a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak on emergency room resident physicians (ERRPs). Methods. We assessed the MERS-related psychological impact and concerns of ERRPs using a self-report questionnaire. Results. The majority (91%) of the ERRPs agreed that their work put them at risk of infection, but most (65%) did not agree that they should not be looking after patients infected with MERS. Despite that, 54% of ERRPs reported being afraid of contracting the infection from infected patients and only 4.2% of them were willing to change their current job. The majority of the ERRPs (85%) felt that their job would expose their families to risk of infection. Conclusions. Our study demonstrated the considerable psychological impact of MERS outbreaks on ERRPs. The ERRPs' concerns and the psychological impact of MERS outbreaks should be considered in greater detail by hospital policymakers.


Psychophysical olfactory testing in COVID‐19: is smell function really impaired in nearly all patients?


title: Applied Clinical Pharmacology in a Crisis – Interleukin‐6 Axis Blockade and COVID‐19

text: The global pandemic of coronavirus disease‐2019 (COVID‐19) represents an emergent threat to the public health. Mitigation strategies have been employed to varying effect in many Western nations. Treatment strategies to effectively address COVID‐19 and equitably distribute resources are needed, especially in overwhelmed hospitals.


title: Dermatological diseases presented before COVID‐19: Are patients with psoriasis and superficial fungal infections more vulnerable to the COVID‐19?

text: Recent studies have focused on the comorbid conditions of the COVID‐19. According to the current studies, numerous diseases including lung disease, cardiovascular disease, and immunosuppression appear to be at higher risk for severe forms of the COVID‐19. To date, there are no data in the literature on the comorbid dermatologic diseases and COVID‐19. We tried to analyze the previous dermatological comorbidity of 93 patients with COVID‐19 (51 males, 42 females) who presented to the dermatology outpatient clinics for the last 3 years. The most common dermatologic diseases in patients with COVID‐19 who have dermatologic diseases for the last three years were superficial fungal infections (24, 25.8%), seborrheic dermatitis (11, 11.8%), actinic keratosis (10, 10.8%), psoriasis (6, 6.5%) and eczema (6, 6.5%), respectively. In addition, the number of COVID‐19 patients who presented to dermatology in the last three months was 17 (11 men, 6 women). The median age of these patients was 58 (minimum 18, maximum 80) years, and the most common dermatologic diseases before diagnosed COVID‐19 were superficial fungal infections (5, 25%), psoriasis (4, 20%), and viral skin diseases (3, 15%). The possible similarity between cutaneous and mucosal immunity and immunosuppression suggests that patients with some dermatologic diseases especially superficial fungal infections and psoriasis may be more vulnerable to the COVID‐19. This article is protected by copyright. All rights reserved.


title: Chapter 3 Routes of Transmission in the Food Chain

text: Abstract More than 250 different foodborne diseases have been described to date, annually affecting about one-third of the world's population. The incidence of foodborne diseases has been underreported and underestimated, and the asymptomatic presentation of some of the illnesses, worldwide heterogeneities in reporting, and the alternative transmission routes of certain pathogens are among the factors that contribute to this. Globalization, centralization of the food supply, transportation of food products progressively farther from their places of origin, and the multitude of steps where contamination may occur have made it increasingly challenging to investigate foodborne and waterborne outbreaks. Certain foodborne pathogens may be transmitted directly from animals to humans, while others are transmitted through vectors, such as insects, or through food handlers, contaminated food products or food-processing surfaces, or transfer from sponges, cloths, or utensils. Additionally, the airborne route may contribute to the transmission of certain foodborne pathogens. Complicating epidemiological investigations, multiple transmission routes have been described for some foodborne pathogens. Two types of transmission barriers, primary and secondary, have been described for foodborne pathogens, each of them providing opportunities for preventing and controlling outbreaks. Primary barriers, the most effective sites of prophylactic intervention, prevent pathogen entry into the environment, while secondary barriers prevent the multiplication and dissemination of pathogens that have already entered the environment. Understanding pathogen dynamics, monitoring transmission, and implementing preventive measures are complicated by the phenomenon of superspreading, which refers to the concept that, at the level of populations, a minority of hosts is responsible for the majority of transmission events.


No evidence for an increased liver uptake of SARS-CoV-2 in metabolic associated fatty liver disease


title: Expression of the hepatitis E virus ORF1

text: Hepatitis E virus (HEV) is an unclassified, plus-strand RNA virus whose genome contains three open reading frames (ORFs). ORF1, the 5′ proximal ORF of HEV, encodes nonstructural proteins involved in RNA replication which share homology with the products of the corresponding ORF of members of the alphavirus-like superfamily of plus-strand RNA viruses. Among animal virus members of this superfamily (the alphavirus and rubivirus genera of the family Togaviridae), the product of this ORF is a nonstructural polyprotein (NSP) that is cleaved by a papain-like cysteine protease (PCP) within the NSP. To determine if the NSP of HEV is similarly processed, ORF1 was introduced into a plasmid vector which allowed for expression both in vitro using a coupled transcription/translation system and in vivo using a vaccinia virus-driven transient expression system. A recombinant vaccinia virus expressing ORF1 was also constructed. Both in vitro and in vivo expression under standard conditions yielded only the full-length 185 kDa polyprotein. Addition of co-factors in vitro, such as divalent cations and microsomes which have been shown to activate other viral proteases, failed to change this expression pattern. However, in vivo following extended incubations (24--36 hours), two potential processing products of 107 kDa and 78 kDa were observed. N- and C-terminus-specific immunoprecipitation and deletion mutagenesis were used to determine that the order of these products within the NSP is NH$_2$-78 kDa-107 kDa-COOH. However, site-specific mutagenesis of Cys(483), predicted by computer alignment to be one member of the catalytic dyad of a PCP within the NSP, failed to abolish this cleavage. Additionally, sequence alignment across HEV strains revealed that the other member of the proposed catalytic dyad of this PCP, His(590), was not conserved. Thus, the cleavage of the NSP observed following prolonged in vivo expression was not mediated by this protease and it is doubtful that a functional PCP exists within the NSP. Attempts to detect NSP expression and processing in HEV-infected primary monkey hepatocytes were not successful and therefore this proteolytic cleavage could not be authenticated. Overall, the results of this study indicate that either the HEV NSP is not processed or that it is cleaved at one site by a virally-encoded protease novel among alpha-like superfamily viruses or a cellular protease.


title: Caring for Tuberculosis Patients: Understanding the Plight of Nurses at a Regional Hospital in Limpopo Province, South Africa

text: Tuberculosis (TB) is a disease which is caused by a relatively large, non-motile, rod-shaped pathogen called Mycobacterium tuberculosis. TB is a major cause of illness and death worldwide, especially in Asia and Africa. Despite the fact that TB is a curable illness, the tragedy is that TB remains the biggest killer in the world as a single pathogen. The aim of this study was to determine the experiences of nurses caring for TB patients at a regional hospital in Limpopo Province, South Africa. Qualitative, exploratory, and descriptive designs were used. A non-probability purposive sampling method was used to select the participants. The personal experiences of six nurses with more than five years’ experience caring for TB patients at a regional hospital were explored, and it was guided by data saturation. Data were collected through in-depth individual interviews. Data were analyzed using Colaizzi’s method. Trustworthiness was ensured and ethical considerations were observed in this study. The research findings revealed six major themes from the raw data: challenges of the working environment, problems impacting on the quality of nursing care, fear, anxiety, stress and risk of contracting infection, nurses’ perceptions towards patients, support structure available in the hospital, and support needs for the nurses. Therefore, there is an urgent need to address the challenges experienced by nurses caring for communicable diseases through provision of a positive practice work environment.


title: Studying the Dynamics of Coronavirus Replicative Structures

text: Coronaviruses (CoVs) generate specialized membrane compartments, which consist of double membrane vesicles connected to convoluted membranes, the so-called replicative structures, where viral RNA synthesis takes place. These sites harbor the CoV replication–transcription complexes (RTCs): multi-protein complexes consisting of 16 nonstructural proteins (nsps), the CoV nucleocapsid protein (N) and presumably host proteins. To successfully establish functional membrane-bound RTCs all of the viral and host constituents need to be correctly spatiotemporally organized during viral infection. Few studies, however, have investigated the dynamic processes involved in the formation and functioning of the (subunits of) CoV RTCs and the replicative structures in living cells. In this chapter we describe several protocols to perform time-lapse imaging of CoV-infected cells and to study the kinetics of (subunits of) the CoV replicative structures. The approaches described are not limited to CoV-infected cells; they can also be applied to other virus-infected or non-infected cells.


Isolation of Porcine Epidemic Diarrhea Virus during Outbreaks in South Korea, 2013–2014


title: Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing

text: Inhalation of nitric oxide (NO) improved arterial oxygenation and enabled the reduction of inspired oxygen therapy and airway pressure support in patients with severe acute respiratory syndrome (SARS). In addition, chest radiography showed decreased spread or density of lung infiltrates, and the physiological effects remained after termination of inhaled NO therapy. These findings suggest not only a pulmonary vasodilator effect of inhaled NO, but also an effect on SARS.


title: Five Questions Critical Care Educators Should Ask About Simulation-Based Medical Education

text: Simulation is now commonly used in health care education, and a growing body of evidence supports its positive impact on learning. However, simulation-based medical education (SBME) involves a range of modalities, instructional methods, and presentations associated with different advantages and limitations. This review aims at better understanding the nature of SBME, its theoretic and proven benefits, its delivery, and the challenges posed by SBME. Areas requiring further research and development are also discussed.


title: Complete genome sequence of bat coronavirus HKU2 from Chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome

text: Abstract Apart from bat-SARS-CoV, we have identified a novel group 1 coronavirus, bat-CoV HKU2, in Rhinolophus sinicus (Chinese horseshoe bats). Since it has been suggested that the receptor-binding motif (RBM) of SARS-CoV may have been acquired from a group 1 coronavirus, we conducted a surveillance study and identified bat-SARS-CoV and bat-CoV HKU2 in 8.7% and 7.5% respectively of R. sinicus in Hong Kong and Guangdong. Complete genome sequencing of four strains of bat-CoV HKU2 revealed the smallest coronavirus genome (27164 nucleotides) and a unique spike protein evolutionarily distinct from the rest of the genome. This spike protein, sharing similar deletions with other group 2 coronaviruses in its C-terminus, also contained a 15-amino acid peptide homologous to a corresponding peptide within the RBM of spike protein of SARS-CoV, which was absent in other coronaviruses except bat-SARS-CoV. These suggest a common evolutionary origin in the spike protein of bat-CoV HKU2, bat-SARS-CoV, and SARS-CoV.


The role of occupational dermatology in the COVID‐19 outbreak


title: Behavioural change models for infectious disease transmission: a systematic review (2010–2015)

text: We review behavioural change models (BCMs) for infectious disease transmission in humans. Following the Cochrane collaboration guidelines and the PRISMA statement, our systematic search and selection yielded 178 papers covering the period 2010–2015. We observe an increasing trend in published BCMs, frequently coupled to (re)emergence events, and propose a categorization by distinguishing how information translates into preventive actions. Behaviour is usually captured by introducing information as a dynamic parameter (76/178) or by introducing an economic objective function, either with (26/178) or without (37/178) imitation. Approaches using information thresholds (29/178) and exogenous behaviour formation (16/178) are also popular. We further classify according to disease, prevention measure, transmission model (with 81/178 population, 6/178 metapopulation and 91/178 individual-level models) and the way prevention impacts transmission. We highlight the minority (15%) of studies that use any real-life data for parametrization or validation and note that BCMs increasingly use social media data and generally incorporate multiple sources of information (16/178), multiple types of information (17/178) or both (9/178). We conclude that individual-level models are increasingly used and useful to model behaviour changes. Despite recent advancements, we remain concerned that most models are purely theoretical and lack representative data and a validation process.


title: Conformational plasticity of the VEEV macro domain is important for binding of ADP-ribose

text: Abstract Venezuelan equine encephalitis virus (VEEV) is a new world alphavirus which can be involved in several central nervous system disorders such as encephalitis and meningitis. The VEEV genome codes for 4 non-structural proteins (nsP), of which nsP3 contains a Macro domain. Macro domains (MD) can be found as stand-alone proteins or embedded within larger proteins in viruses, bacteria and eukaryotes. Their most common feature is the binding of ADP-ribose (ADPr), while several macro domains act as ribosylation writers, erasers or readers. Alphavirus MD erase ribosylation but their precise contribution in viral replication is still under investigation. NMR-driven titration experiments of ADPr in solution with the VEEV macro domain (in apo- and complex state) show that it adopts a suitable conformation for ADPr binding. Specific experiments indicate that the flexibility of the loops β5-α3 and α3-β6 is critical for formation of the complex and assists a wrapping mechanism for ADPr binding. Furthermore, along with this sequence of events, the VEEV MD undergoes a conformational exchange process between the apo state and a low-populated “dark” conformational state.


title: Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a carbamoyl linker

text: Abstract 5-Arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesised from N-methyl-C-diethoxyphosphorylnitrone and N-arylacrylamides in good yields. cis- and trans-isoxazolidine phosphonates obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. Isoxazolidines having phenyl substituted with halogen (Ar=2-F-C6H4; 3-Br-C6H4; and 4-Br-C6H4) have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC50 in the 100–170μM range.


title: Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti‐viral activity

text: Side effects of interferon–ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications. The aim of this study was to evaluate the efficacy of a hemoglobin–ribavirin conjugate (HRC 203) in murine hepatitis virus strain 3 (MHV‐3) induced viral hepatitis. HRC 203 had greater anti‐viral activity on both isolated hepatocytes and macrophages, whereas both ribavirin and HRC 203 inhibited production of the pro‐inflammatory cytokines interferon gamma (IFN‐γ) and tumor necrosis factor alpha (TNF‐α) by macrophages. In vivo, untreated MHV‐3–infected mice all developed clinical and biochemical signs of acute viral hepatitis and died by day 4 post infection. Livers recovered from untreated infected mice showed greater than 90% necrosis. In contrast, survival was enhanced in both ribavirin‐ and HRC 203–treated mice with a marked reduction in biochemical [ALT(max) 964 ± 128 IU/L (ribavirin); 848 ± 212 IU/L (HRC 203)] and histological evidence of hepatic necrosis (<10% in ribavirin/HRC 203 vs. 90% in untreated controls). Clinically, HRC 203–treated mice behaved normally, in contrast to ribavirin‐treated mice, which developed lethargy and abnormal fur texture. In conclusion, targeted delivery of ribavirin to the liver alters the course of MHV‐3 infection as demonstrated by prolonged survival, improved behavior, and reduced signs of histologically evident disease, as well as inhibition of viral replication and production of inflammatory cytokines in vitro. (Hepatology 2006;43:581–591.)


title: Performance of materials used for biological personal protective equipment against blood splash penetration

text: For occupational safety, healthcare workers must select and wear appropriate personal protective equipment (PPE), protective clothing, and masks as countermeasures against exposure to infectious body fluids and blood splash. It is important for healthcare workers to ensure the protective performance of each PPE against penetration of pathogens. The International Standards Organization (ISO) 22609 test evaluates the effectiveness of medical facemasks to protect against penetration of splashed synthetic blood. However, in this method, the protective performance is determined only visually, without quantification of leaked liquid volume. Therefore, in this study, we modified the ISO 22609 test method to quantify the volume of leaked liquid and obtain a more accurate assessment of the protection performance. We tested non-woven and woven materials used for masks or protective clothing, and the performance of each material was classified using this new method. We found that the quantity of leaked synthetic blood was dependent on the structural characteristics of each material. These findings will allow healthcare workers to select the most appropriate PPE for a given situation or task.


title: All those D‐dimers in COVID‐19

text: One of the most consistent abnormal haemostatic laboratory markers in COVID‐19 is raised D‐dimers. Increased D‐dimers have also been observed in several studies published in the Journal of Thrombosis and Haemostasis to have prognostic implications.(1,2) But some of the perplexing questions in this regard are what may be the reasons for such marked elevation in D‐dimers and may it have any ‘useful’ purpose apart from prognostication?


title: COVID-19 and the male susceptibility: the role of ACE2, TMPRSS2 and the androgen receptor

text: Abstract COVID-19 is the pandemic that hit the world starting December 2019. Recent studies and international statistics have shown an increased prevalence, morbidity as well as mortality of this disease in male patients compared to female patients. The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor. This could help understand the susceptibility of urological patients, especially those receiving androgen deprivation therapy for prostate cancer, and testosterone replacement therapy.


title: Quest for a COVID-19 Cure by Repurposing Small-Molecule Drugs: Mechanism of Action, Clinical Development, Synthesis at Scale, and Outlook for Supply

text: [Image: see text] The outbreak of the COVID-19 pandemic has spurred an intense global effort to repurpose existing approved drugs for its treatment. In this review, we highlight the development of seven small-molecule drugs that are currently being assessed in clinical trials for the treatment of COVID-19. Three sections are presented for each drug: (1) history, mechanism of action, and status of clinical trials; (2) scalable synthetic routes and final forms; and (3) outlook for supply should clinical trials show treatment efficacy. A brief overview of diagnostic testing and vaccine development is also presented.


title: COVID-19 and Laparoscopic Surgery: Scoping Review of Current Literature and Local Expertise

text: BACKGROUND: The current coronavirus disease (COVID-19) pandemic is holding the world in its grip. Epidemiologists have shown that the mortality risks are higher when the health care system is subjected to pressure from COVID-19. It is therefore of great importance to maintain the health of health care providers and prevent contamination. An important group who will be required to treat patients with COVID-19 are health care providers during semiacute surgery. There are concerns that laparoscopic surgery increases the risk of contamination more than open surgery; therefore, balancing the safety of health care providers with the benefit of laparoscopic surgery for the patient is vital. OBJECTIVE: We aimed to provide an overview of potential contamination routes and possible risks for health care providers; we also aimed to propose research questions based on current literature and expert opinions about performing laparoscopic surgery on patients with COVID-19. METHODS: We performed a scoping review, adding five additional questions concerning possible contaminating routes. A systematic search was performed on the PubMed, CINAHL, and Embase databases, adding results from gray literature as well. The search not only included COVID-19 but was extended to virus contamination in general. We excluded society and professional association statements about COVID-19 if they did not add new insights to the available literature. RESULTS: The initial search provided 2007 records, after which 267 full-text papers were considered. Finally, we used 84 papers, of which 14 discussed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eight papers discussed the added value of performing intubation in a low-pressure operating room, mainly based on the SARS outbreak experience in 2003. Thirteen papers elaborated on the risks of intubation for health care providers and SARS-CoV-2, and 19 papers discussed this situation with other viruses. They conclude that there is significant evidence that intubation and extubation is a high-risk aerosol-producing procedure. No papers were found on the risk of SARS-CoV-2 and surgical smoke, although 25 papers did provide conflicting evidence on the infection risk of human papillomavirus, hepatitis B, polio, and rabies. No papers were found discussing tissue extraction or the deflation risk of the pneumoperitoneum after laparoscopic surgery. CONCLUSIONS: There seems to be consensus in the literature that intubation and extubation are high-risk procedures for health care providers and that maximum protective equipment is needed. On the other hand, minimal evidence is available of the actual risk of contamination of health care providers during laparoscopy itself, nor of operating room pressure, surgical smoke, tissue extraction, or CO(2) deflation. However, new studies are being published daily from current experiences, and society statements are continuously updated. There seems to be no reason to abandon laparoscopic surgery in favor of open surgery. However, the risks should not be underestimated, surgery should be performed on patients with COVID-19 only when necessary, and health care providers should use logic and common sense to protect themselves and others by performing surgery in a safe and protected environment.


title: Identification of immunogenic determinants of the spike protein of SARS-like coronavirus

text: Bat SARS-like coronavirus (SL-CoV) has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike (S) proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63–64% sequence identity. Although there have been reports studying the overall immunogenicity of S(SL), knowledge on the precise location of immunodominant determinants for S(SL) is still lacking. In this study, using a series of truncated expressed S(SL) fragments and S(SL) specific mouse sera, we identified two immunogenic determinants for S(SL). Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the S(SARS). This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.


Laboratory biosafety guide for 2019-nCoV (Second Edition)


title: Co-detection of Pandemic (H1N1) 2009 Virus and Other Respiratory Pathogens

text: From May through October 2009, a total of 10,624 clinical samples from 23 US states were screened for multiple respiratory pathogen gene targets. Of 3,110 (29.3%) samples positive for pandemic (H1N1) 2009 virus, 28% contained >1 other pathogen, most commonly Staphylococcus aureus (14.7%), Streptococcus pneumoniae (10.2%), and Haemophilus influenzae (3.5%).


title: Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease

text: BACKGROUND: Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. OBJECTIVES: The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. METHODS: Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 μm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. RESULTS: Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. CONCLUSIONS: This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.


title: A Study of the Use and Outcomes From Respiratory Viral Testing at a Mid-Sized Children’s Hospital

text: This study was a retrospective analysis of inpatient and emergency department (ED) data on respiratory pathogen panel (RPP) testing between December 16, 2013, and December 15, 2015, at a mid-sized children’s hospital. We assessed whether RPP decreases antibiotic days of therapy and length of hospital stay for pediatric patients with acute respiratory infections. In the inpatient population, patients testing positive with RPP were given fewer antibiotic days of therapy (2.99 vs 4.30 days; P = .032) and had shorter hospital stays (2.84 vs 3.80 days; P = .055) than patients testing negative. In the ED population, patients testing positive with RPP received fewer discharge prescriptions for antibiotics than patients not tested (8.8% vs 41.1%; P < .001). RPP use was more prevalent in admitted patients than in ED patients (78.9% vs 7.3%; P < .001). Our results suggest that RPP testing curbs antibiotic use and decreases length of hospital stay.


Recommendations on contingency operations for hospitals in response to COVID-19 cases identified in inpatients – Taiwan


Surveillance for Coronaviruses in Bats, Lebanon and Egypt, 2013–2015


title: Vaccine Target Discovery

text: Abstract With the rise in novel infectious agents and disease pandemics, a new era of vaccine discovery is necessary. To address this, the new field of immunomics is described, which is synergistically powered by integrating bioinformatics methodologies with technological advances in biology and high-throughput instrumentation. By incorporating biological data from immunology and molecular biology with current genomics and proteomics, immunomics is geared to deliver an insight into immune function, optimal stimulation of immune responses and precise mapping and rational selection of immune targets that cover antigenic diversity. These efforts are expected to contribute towards the development of new generation of vaccines, tailored to both the genetic make-up of the human population and of the pathogen. Vaccine technologies are also being explored for prevention or control of non-communicable diseases.


title: Direct endotracheal intubation using a novel detachable optic probe (Sunscope) by emergency medical technicians with various training backgrounds

text: Abstract Objective Effective airway management requires both proper technique and the appropriate devices. With the widespread implementation of advanced life-support techniques in emergency medical services (EMS), orotracheal intubation is now performed not only by professional practitioners but, in many occasions, nonprofessionals. With extensively diversified skill equipped, we tested whether the Sunscope, a patented tracheal intubation device with a digital display, is able to facilitate tracheal intubation by naïve EMS personnel with various training backgrounds. Methods We conducted a study to determine rate of success and time required to insert an orotracheal tube into a mannequin using Sunscope. The participants were placed into the professional group (i.e., anesthesiologists and emergency medical paramedics; EMT-P) or the nonprofessional group (i.e., emergency medical technicians; EMT). Intubation required three steps: equipment preparation, vocal cord exposure, and tube insertion. The time required for each step was recorded by a senior staff member, and the data were analyzed by nonparametric statistics. Results Each consecutive step in the operating procedure was significantly shorter for the professional group in comparison with the nonprofessional group during the first trial: equipment preparation, 10.5 ± 2.1 vs. 11.9 ± 4.1 seconds; vocal cord exposure, 7.4 ± 7.7 vs. 12.2 ± 7.7 seconds; tube insertion, 8.8 ± 4.8 vs. 17.6 ± 9.4 seconds; and total time required for intubation, 26.7 ± 8.8 vs. 35.8 ± 19.6 seconds. The professional practitioners showed no significant improvement, in terms of time reduction, on the following three trials. On the other hand, the nonprofessional practitioners showed no significant differences, in terms of time required to expose the vocal cords and total operation time, following the third trial in comparison with the professional practitioners. Conclusion Our research demonstrates that professional practitioners are able to use the Sunscope on their first attempt. Despite a lack of training in conventional endotracheal intubation, emergency medical technicians (EMT-I and -II) were able to complete intubation on their first attempt; a significant reduction in the time required to intubate was noted after repeated practice. All levels of naïve EMTs were able to readily visualize the vocal cords through Sunscope and, thereby, reliably insert the endotracheal tube in less than 1 minute, regardless of their skills before testing.


title: Idiopathic sclerosing orbital pseudotumor in seven cats

text: Objective To review the clinical presentation and histopathologic findings on a series of cats with orbital fibrotic disease and compare the data to that of humans with sclerosing orbital pseudotumor. Animals A retrospective study was undertaken, which identified tissue samples from seven cats between 1997 and 2002 with a history of orbital mass effect and pathology characterized by fibrous tissue proliferation. Procedure Information was obtained from medical records for affected cats, including age, sex, clinical signs, management, and outcome, with histopathology re‐examined. Results Six of seven cats presented with unilateral orbital involvement that progressed to bilateral orbital disease despite treatment. Onset was insidious, evolving over weeks to months and was associated with fixation of orbital structures. Owners of six of the cats opted for euthanasia because of disease progression and pain. Histopathology of affected orbital tissue included extensive fibrosis with encapsulation of normal tissues without characteristics of neoplasia. Conclusions Clinical findings and histopathology of globes and orbital tissues in cats bore many similarities to idiopathic sclerosing orbital pseudotumor in humans. In cats, the prognosis for the globe appears to be poor but an elucidation of the pathogenesis and earlier diagnosis coupled with more aggressive treatment modalities as indicated in humans may be beneficial.


title: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

text: Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.


title: Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk

text: Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. Their structures were established by chemical tests and detailed spectroscopic analysis as 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (1), 7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (2) and 7,8-didehydro-24S-O-acetylhydroshengmanol-3-O-β-D-galactopyranoside (3), respectively.


title: A non-contact infection screening system using medical radar and Linux-embedded FPGA: Implementation and preliminary validation

text: Abstract Objectives In this study, an infection screening system was developed to detect patients suffering from infectious diseases. In addition, the system was also designed to deal with the variability in age and gender, which would affect the accuracy of the detection. Furthermore, to enable a low-cost, non-contact and embedded system, multiple vital signs from a medical radar were measured and all algorithms were implemented on a Field Programmable Gate Array, named PYNQ-Z1. Methods The system consisted of two main stages: digital signal processing and data classification. In the former stage, Butterworth filters, with flexible cut-off frequencies depending on age and gender, and a time-domain peak detection algorithm were deployed to compute three vital signs, namely heart rate, respiratory rate, and standard deviation of heart beat-to-beat interval. For the classification problem, two machine learning models, Support Vector Machine and Quadratic Discriminant Analysis, were implemented. Results The Student's t-test showed that our proposed digital signal processing algorithms coped well with the variability of human cases in age and gender. Meanwhile, the f1-score of roughly 98.0% represented the high sensitivity and specificity of our proposed machine learning methods. Conclusion This study outlines the implementation of an infection screening system, which achieved competent performance. The system might be beneficial for fast screening of infected patients at public health centers in underdeveloped areas, where people have little access to healthcare.