title: Differentiated phenotypes of primary murine alveolar epithelial cells and their susceptibility to infection by respiratory viruses

text: Severe respiratory viral infections are associated with spread to the alveoli of the lungs. There are multiple murine models of severe respiratory viral infections that have been used to identify viral and host factors that contribute to disease severity. Primary cultures of murine alveolar epithelial cells provide a robust in vitro model to perform mechanistic studies that can be correlated with in vivo studies to identify cell type-specific factors that contribute to pathology within the alveoli of the lung during viral infection. In this study, we established an in vitro model to compare the responses of type I (ATI) and type II (ATII) alveolar epithelial cells to infection by respiratory viruses used in murine models: mouse-adapted severe acute respiratory syndrome-associated coronavirus (SARS-CoV, v2163), murine coronavirus MHV-1, and influenza A (H1N1) virus, strain PR8. Murine alveolar cells cultured to maintain an ATII cell phenotype, determined by expression of LBP180, were susceptible to infection by all three viruses. In contrast, ATII cells that were cultured to trans-differentiate into an ATI-like cell phenotype were susceptible to MHV-1 and PR8, but not mouse-adapted SARS-CoV. Epithelial cells produce cytokines in response to viral infections, thereby activating immune responses. Thus, virus-induced cytokine expression was quantified in ATI and ATII cells. Both cell types had increased expression of IL-1β mRNA upon viral infection, though at different levels. While MHV-1 and PR8 induced expression of a number of shared cytokines in ATI cells, there were several cytokines whose expression was induced uniquely by MHV-1 infection. In summary, ATI and ATII cells exhibited differential susceptibilities and cytokine responses to infection by respiratory viruses. This in vitro model will be critical for future studies to determine the roles of these specialized cell types in the pathogenesis of respiratory viral infection.


title: A questionnaire-based survey on the uptake and use of cattle vaccines in the UK

text: BACKGROUND: Vaccination is a widely used strategy for disease control in cattle in the UK and abroad. However, there has been limited research describing the uptake and use of cattle vaccines on UK farms. AIM: To describe the current uptake and usage of cattle vaccines in the UK. DESIGN: A questionnaire, available in paper and online format, was distributed to cattle farmers by convenience sampling. PARTICIPANTS: All UK cattle farmers were eligible to participate in the study. RESULTS: Eighty-six per cent of respondents (n=229/266) had vaccinated their cattle in the past year. Diseases most commonly vaccinated against were Bovine Viral Diarrhoea, Leptospirosis and Infectious Bovine Rhinotracheitis. Vaccination compliance was limited in certain areas, for example only 48 per cent of respondents stated that they administered the second dose in the primary course within the recommended timeframe, and 14 per cent of respondents stated that they vaccinated earlier than the youngest recommended age. Although outside the scope of this study, further work is needed to establish the extent of inadequate compliance and the effect this has on vaccine efficacy. The role of the veterinarian was highlighted as the main supplier of vaccines and preferred source of vaccination information. Respondents preferred to receive recommendations regarding vaccination by face-to-face communication with the veterinarian. CONCLUSIONS: The results provide a description of the current uptake and usage of cattle vaccines in the UK. Uptake is generally high but there are areas of usage of vaccines which could be improved upon. The veterinarian plays a key role as supplier of vaccines and a source of information for the majority of farmers. Although outside the scope of this study, further work is needed to establish the extent of inadequate compliance and the effect this has on vaccine efficacy. Although the respondents in this study represent a biased population of farmers, the findings indicate areas for future investigation in order to improve vaccination strategies in cattle in the UK.


title: Innovative Preventive and Resilience Approaches Against Aedes-linked Vector-borne Arboviral Diseases Threat and Epidemics Burden in Gulf Council Countries

text: Facing the local and imported borderless Aedes-linked vector-borne viral diseases threat and epidemics burden, the Health Committee of the Gulf Cooperation Council (GCC), including the Saudi Arabian government, announced that all Gulf countries are still free from the threat of a Zika virus epidemic. This article provides a vision of integrated eco-friendly and sustainable behavioral communication change (BCC), biological control preparedness and resilience approaches, and innovations implementation in Saudi Arabia and GCC for the purpose of controlling the threat of Aedes-linked vector-borne viral diseases. Implementing innovative Aedes-linked arboviral preventive and resilient control measures is pivotal in improving community-based surveillance-response systems, BCC multidisciplinary and empowerment methods, and in enhancing community social mobilization and risk communication strategies. Moreover, boosting social, cultural and ecological preparedness, and prompt management approaches are necessary against the threat of local and global zoonotic epidemics and pandemics. Nurturing evidence and proven tick or mosquito vector populations' reduction, planned urbanization, climate change and waste management systems, and implementing data sharing and tailored mitigation solutions are crucial against the persisting Aedes competence and the public health threat of dengue, MERS-CoV, and influenza outbreaks. Sustained investment and ample financial allocation are needed to improve Muslim pilgrimage (Hajj and Umrah mass gathering) including point of entry screening and treatment, community-based education and awareness campaigns, and increasing mosquito vector viral pathogens surveillance interventions. Increasing evidence-based population participation and resilient emergency community preparedness and rapid response programs integration are critical to reduce mosquito breeding sites, dengue, and other arboviral infections.


title: Coronavirus (COVID-19) – An epidemic or pandemic for financial markets

text: The novel Coronavirus disease (COVID-19) has quickly evolved from a provincial health scare to a global meltdown. While it has brought nearly half the world to a standstill it has affected the financial markets in unseen ways by eroding a quarter of wealth in nearly a month. This paper investigates the reaction of financial markets globally in terms of their decline and volatility as Coronavirus epicentre moved from China to Europe and then to the US. Findings suggest that the earlier epicentre China has stabilised while the global markets have gone into a freefall especially in the later phase of the spread. Even the relatively safer commodities have suffered as the pandemic moves into the US.


title: Characterization of Chinese Porcine Epidemic Diarrhea Virus with Novel Insertions and Deletions in Genome

text: Outbreaks of porcine epidemic diarrhoea virus (PEDV) have caused great economic losses to the global pig industry. PEDV strains with variants in the spike (S) gene have been reported in several countries. To better understand the molecular epidemiology and genetic diversity of PEDV field isolates, in this study, we characterised the complete genome sequence of a novel PEDV variant JSCZ1601 from a outbreak in China in 2016. The PEDV isolate was 28,033 nucleotides (nt) in length without the polyadenylated sequences. Phylogenetic analysis based on the full-length genome sequence of JSCZ1601 grouped it with the pandemic variants determined post-2010 into group 2 (G2). However, the S gene of JSCZ1601 formed a new subgroup separated from the subgroups containing the other G2 strains. Comparative analysis of the amino acids encoded by the S genes revealed the N-terminal of the deduced JSCZ1601 S protein had a novel two-amino-acid deletion (N58 and S59) compared with all identified genogroups. Further, compared with the reference strains, a ‘G’ insertion was detected in the 5′ terminal of the 5′UTR of the JSCZ1601. The animal experiment revealed that this strain was high pathogenic to neonatal pigs. Taken together, a PEDV strain with the new molecular characterizations and phylogenies was found in mainland China. It is necessary to strengthen the monitoring of PEDV variations.


Non‐complicated evolution of COVID‐19 infection in a patient with psoriasis and psoriatic arthritis during treatment with adalimumab


Implications du COVID-19 pour la prise en charge des rhumatismes inflammatoires chroniques


title: Reflections from London’s Level-1 Major Trauma Centres during the COVID crisis

text: Emergence of the Covid-19 pandemic resulted in dramatic changes in global healthcare provision. Resources were redirected across all healthcare sectors to support the treatment of viral pneumonia with resultant effects on other essential services. We describe the impact of this on the provision of major trauma care in a major capital city.


Early nutritional management in non-critically ill coronavirus disease 2019 patients


title: A Preliminary Study to Determine Comprehensive Research and Development Plans for Promoting Mental Health Services

text: OBJECTIVES: The aim of this study was to analyze research and development projects in mental health services in Korea, using priority evaluation of mental health promotion policies to determine direction of the service. METHODS: An online survey was conducted that targeted experts in the mental health service regarding promotion of mental health in Korea in 2016. The survey was based on 32 policy projects that resulted from 12 strategies according to 4 policy objectives. RESULTS: Analysis of 32 mental health projects were assessed regarding the possibility of technology development success, magnitude of the ripple effect, and necessity of a national response. It was observed that 3 policy projects relevant to suicide, had a high relative priority. This was followed by policies for improvement of health insurance and the medical benefit cost system, and policies for reinforcement of crisis psychological support such as those for disaster victims. CONCLUSION: The prioritization of mental health services should place an emphasis on promotion of a healthy mental lifestyle, rehabilitation support for patients with serious mental illness, and reinforcement of social safety networks for suicide prevention.


title: Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients

text: The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly-diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, especially short and medium chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, and mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading, RBCs from COVID-19 patients may be incapable of responding to environmental variations in hemoglobin oxygen saturation when traveling from the lungs to peripheral capillaries and, as such, may have a compromised capacity to transport and deliver oxygen.


title: Infectious Bronchitis Virus induces acute interferon-gamma production through polyclonal stimulation of chicken leukocytes

text: Abstract Infectious Bronchitis Virus, a member of the Coronaviridae, is a respiratory pathogen in poultry. We found that in vitro stimulation with IBV resulted in ChIFN-γ production in splenocytes of both infected birds and uninfected birds. The non-specific stimulation did not occur when other avian viruses or other coronaviruses were used or when mammalian cells were stimulated with IBV. Inactivation of IBV reduced ChIFN-γ production, but ChIFN-γ remained elevated compared to unstimulated cells. An increase in ChIFN-γ mRNA was detected in splenocytes from IBV-infected and uninfected chickens as early as 1 h after stimulation with IBV. These results indicate that IBV acts as a polyclonal stimulus, inducing a rapid production of IFN-γ even without previous exposure to the virus.


SARS-CoV-2 pandemic and pediatric endoscopic surgery


title: Detection and phylogenetic analysis of porcine epidemic diarrhea virus in central China based on the ORF3 gene and the S1 gene

text: BACKGROUND: Porcine epidemic diarrhea (PED) has increased in severity in China since 2010. To investigate further the infectivity, genetic diversity and molecular epidemiology of its causative agent, the porcine epidemic diarrhea virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue of piglets with severe diarrhea, from 17 cities in central China. Both the spike (S) glycoprotein (S1, 1–789 amino acids (aa)) and the full-length ORF3 gene of 21 representative field strains from 21 farms in 11 cities were sequenced and analysed. METHODS: PEDV was detected by reverse transcription-polymerase chain reaction (RT-PCR), and S1 and ORF3 sequences were processed by the Clustal W method via DNAMAN 8 software, and phylogenetic trees were constructed by the neighbor-joining method using MEGA 6 software. RESULTS: The prevalence of PEDV was 92.25% and was detected in 119 of 129 samples, with 94.03% (63 of 67) of pig farms harbouring the disease. According to the phylogenetic analysis of the S1 genes, our isolates all fell into group G2 (variants) and showed a close relationship to isolates from Chinese (HN1303, CH/ZMDZY/11 and AJ1102), Korean (AD01), American (MN, IA1, IA2 and 13–019349) sources, and these isolates differed genetically from other Chinese (LZC, CH/HNZZ/2011 and SD-M) and Korean (SM98) strains as well Japanese (83-P5 and MK) strains. In addition, our isolates differed from attenuated vaccine strains, CV777 (used in China) and DR13 (used in Korea). According to our derived amino acid sequence analysis, we detected one novel variant PEDV, viz: CH/HNLY, with 4-aa insertion/deletion (RSSS/T) at position 375 and 1-aa (D) deletion at position 430 compared to the CV777 attenuated strain. These mutations were located on the receptor binding domain. Our ORF3 gene analyses showed that the prevalent PEDV isolates were variants, and the isolated strains differed genetically from the vaccine strains. CONCLUSIONS: These findings illustrated the existence of genetic diversity among geographically distinct PEDV strains, and our study has provided an impetus to conduct further research on the PEDV receptor binding protein and on the new and efficacious vaccines design. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0646-8) contains supplementary material, which is available to authorized users.


title: Epidemiology of human adenovirus infection in children hospitalized with lower respiratory tract infections in Hunan, China

text: To investigate the current genotypes of circulating human adenovirus (HAdV) strains, we molecularly genotyped HAdV in the nasopharyngeal aspirates (NPAs) of patients with acute lower respiratory tract infections (ALRTIs) and attempted to determine their associations with clinical symptoms. A total of 4751 NPA samples were collected from 4751 patients admitted to Hunan Provincial People's Hospital from September 2007 to March 2014, of which 447 (9.4%) samples were HAdV positive. Fourteen different HAdV types were identified; HAdV types 1 to 7 (HAdV 1‐7) were identified in 95.7% of the 447 NPA samples with HAdV‐7 and HAdV‐3 being the most prevalent. In addition, 93.3% (417 of 447) of patients were younger than 5 years. The incidence of HAdV infection peaked in summer. Different HAdV types showed a predilection for different age groups and different seasonal distribution patterns. Coinfection of HAdVs and other respiratory viruses was detected in 63.3% (283 of 447) of the HAdV‐positive samples. The most common clinical diagnosis was pneumonia and the most common symptoms were fever and cough. In comparison with children infected with HAdV‐3 alone, those infected with HAdV‐7 alone had an increased frequency of severe pneumonia involvement (11.6% vs 32.4%; P = 0.031), higher intensive care unit admission rates (7.0% vs 26.5%; P = 0.019), and a longer length of hospital stay (P = 0.03). Mixed infections in younger children were associated with a longer hospital stay (P = 0.023). Our results demonstrate the recent changes in the trends of circulating HAdV genotypes associated with ALRTIs in Hunan China.


Hochdosiertes Chloroquin bei COVID-19 gefährlich


title: Complemented palindrome small RNAs first discovered from SARS coronavirus

text: In this study, we reported for the first time the existence of complemented palindrome small RNAs (cpsRNAs) and proposed cpsRNAs and palindrome small RNAs (psRNAs) as a novel class of small RNAs. The first discovered cpsRNA UCUUUAACAAGCUUGUUAAAGA from SARS coronavirus named SARS-CoV-cpsR-22 contained 22 nucleotides perfectly matching its reverse complementary sequence. Further sequence analysis supported that SARS-CoV-cpsR-22 originated from bat betacoronavirus. The results of RNAi experiments showed that one 19-nt segment of SARS-CoV-cpsR-22 significantly induced cell apoptosis. These results suggested that SARS-CoV-cpsR-22 could play a role in SARS-CoV infection or pathogenicity. The discovery of psRNAs and cpsRNAs paved the way to find new markers for pathogen detection and reveal the mechanisms in the infection or pathogenicity from a different point of view. The discovery of psRNAs and cpsRNAs also broaden the understanding of palindrome motifs in animal of plant genomes.


title: Viral–Bacterial Interactions in Acute Otitis Media

text: Acute otitis media (AOM) is a polymicrobial disease, which usually occurs as a complication of viral upper respiratory tract infection (URI). While respiratory viruses alone may cause viral AOM, they increase the risk of bacterial middle ear infection and worsen clinical outcomes of bacterial AOM. URI viruses alter Eustachian tube (ET) function via decreased mucociliary action, altered mucus secretion and increased expression of inflammatory mediators among other mechanisms. Transient reduction in protective functions of the ET allows colonizing bacteria of the nasopharynx to ascend into the middle ear and cause AOM. Advances in research help us to better understand the host responses to viral URI, the mechanisms of viral–bacterial interactions in the nasopharynx and the development of AOM. In this review, we present current knowledge regarding viral–bacterial interactions in the pathogenesis and clinical course of AOM. We focus on the common respiratory viruses and their established role in AOM.


title: Predicting Super Spreading Events during the 2003 Severe Acute Respiratory Syndrome Epidemics in Hong Kong and Singapore

text: One of the intriguing characteristics of the 2003 severe acute respiratory syndrome (SARS) epidemics was the occurrence of super spreading events (SSEs). Here, the authors report the results of identifying the occurrence of SSEs in the Hong Kong and Singapore epidemics using mathematical and statistical analysis. Their predicted occurrence of SSEs agreed well with the reported occurrence of all seven super spreaders in the two cities. Additional unidentified SSEs were also found to exist. It was found that 71.1% and 74.8% of the infections were attributable to SSEs in Hong Kong and Singapore, respectively. There also seemed to be “synchronized” occurrences of infection peaks in both the community and the hospitals in Hong Kong. The results strongly suggested that the infection did not depend on the total number of symptomatic cases, with only a very small proportion of symptomatic individuals being shown to be infectious (i.e., able to infect other individuals). The authors found that the daily infection rate did not correlate with the daily total number of symptomatic cases but with the daily number of symptomatic cases who were not admitted to a hospital within 4 days of the onset of symptoms.


title: Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection

text: Lack of effective treatment strategy and vaccine makes SARS-CoV-2 infection a big threat to mankind. Analyzing the host transcriptional changes in response to virus infection will help delineate the biological processes impacted by the virus and will potentially facilitate drug development. Using RNA seq datasets of virus infected lung cell lines A549 (infected with either SARS-CoV-2 or Influenza A virus (IAV)) and Calu3 (infected with either SARS-CoV-2 or MERS-CoV), we present a detailed analysis of genes expression changes in response to each of these viral infections. Upregulation of the antiviral interferon signaling was observed with all three viral infections. However, upregulation of the cytokine/inflammatory processes, downregulation of mitochondrial organization and respiration processes, and perturbation in the autophagic processes were specifically observed in SARS-CoV-2 infected cells, which were absent in IAV infected cells. Upregulation of the inflammatory processes was concordant with the gene expression signature of COVID-19 lungs and with inflammatory symptoms observed in severe cases of COVID-19 patients. Coexpression networks analysis also facilitated the identification of protein-protein interaction (PPI) subnetworks of genes in the inflammation and mitochondrial processes that were either coordinately up or downregulated in SARS-CoV-2 infected cells, respectively. Comparing the expression of marker genes of lung cell types from single cell RNA seq data with expression profile of A549 cells revealed that they likely represent the lung epithelial lineage cells. The cellular processes uniquely perturbed in infected cells that were identified in this analysis likely delineates lung epithelial cells response to the SARS-CoV-2 infection.


title: Kawasaki disease: pathophysiology and insights from mouse models

text: Kawasaki disease is an acute febrile illness and systemic vasculitis of unknown aetiology that predominantly afflicts young children, causes coronary artery aneurysms and can result in long-term cardiovascular sequelae. Kawasaki disease is the leading cause of acquired heart disease among children in the USA. Coronary artery aneurysms develop in some untreated children with Kawasaki disease, leading to ischaemic heart disease and myocardial infarction. Although intravenous immunoglobulin (IVIG) treatment reduces the risk of development of coronary artery aneurysms, some children have IVIG-resistant Kawasaki disease and are at increased risk of developing coronary artery damage. In addition, the lack of specific diagnostic tests and biomarkers for Kawasaki disease make early diagnosis and treatment challenging. The use of experimental mouse models of Kawasaki disease vasculitis has considerably improved our understanding of the pathology of the disease and helped characterize the cellular and molecular immune mechanisms contributing to cardiovascular complications, in turn leading to the development of innovative therapeutic approaches. Here, we outline the pathophysiology of Kawasaki disease and summarize and discuss the progress gained from experimental mouse models and their potential therapeutic translation to human disease.


title: The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation

text: Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation.


Nonstructural Proteins of Human Coronavirus NL63


title: Viral Short ORFs and Their Possible Functions

text: Definition of functional genomic elements is one of the greater challenges of the genomic era. Traditionally, putative short open reading frames (sORFs) coding for less than 100 amino acids were disregarded due to computational and experimental limitations; however, it has become clear over the past several years that translation of sORFs is pervasive and serves diverse functions. The development of ribosome profiling, allowing identification of translated sequences genome wide, revealed wide spread, previously unidentified translation events. New computational methodologies as well as improved mass spectrometry approaches also contributed to the task of annotating translated sORFs in different organisms. Viruses are of special interest due to the selective pressure on their genome size, their rapid and confining evolution, and the potential contribution of novel peptides to the host immune response. Indeed, many functional viral sORFs were characterized to date, and ribosome profiling analyses suggest that this may be the tip of the iceberg. Our computational analyses of sORFs identified by ribosome profiling in DNA viruses demonstrate that they may be enriched in specific features implying that at least some of them are functional. Combination of systematic genome editing strategies with synthetic tagging will take us into the next step—elucidation of the biological relevance and function of this intriguing class of molecules.


title: Polymerase‐chain‐reaction‐based diagnosis of viral pulmonary infections in immunocompromised children

text: AIM: Viral pneumonia is a serious complication in immunocompromised children. Its aetiology is difficult to identify owing to the limitations of conventional microbiological tests. The aim of this study was to determine whether polymerase chain reaction (PCR) assays for respiratory viruses increase the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised children. METHODS: BAL samples obtained from immunocompromised children hospitalized with pneumonia were processed for respiratory viruses by viral culture, rapid antigen test and PCR (for CMV, adenovirus, influenza, parainfluenza, herpesvirus, RSV and hMPV). RESULTS: The study group included 42 patients (mean age 7.2 ± 5.1 years) with 50 episodes of clinical pneumonia (50 BAL samples). Forty viral pathogens were identified in 30 episodes (60%). PCR increased the diagnostic rate by fourfold (75% identified by PCR alone, p < 0.0001). When viral culture and rapid antigen test were used as the gold standard, PCR was found to have high sensitivity (86–100% when assessed) and specificity (80–96%). The PCR results prompted the initiation of specific antiviral therapy and the avoidance of unnecessary antibiotic treatment in 17 (34%) episodes. CONCLUSION: PCR‐based diagnosis from BAL may increase the rate of pathogen detection in immunocompromised children, decrease the time to diagnosis and spare patients unnecessary antimicrobial treatment.


Mitteilungen der DGPPN 5/2020


title: COVID-19 as a Vascular Disease: Lesson Learned from Imaging and Blood Biomarkers

text: COVID-19, a disease initially thought to be prominently an interstitial pneumonia with varying degrees of severity, can be considered a vascular disease with regards to serious complications and causes of mortality Quite recently, blood clots have emerged as the common factor unifying many of the symptoms initially attributed without an explanation to COVID-19 Cardiovascular biomarkers and particularly, D-dimer and troponin appear to be very powerful prognostic markers, signaling the need for earlier and more aggressive interventions and treatments in order to avoid and/or minimize arterial/venous thromboembolism and myocardial infarct The ultrasound imaging patterns at both the lung and peripheral vascular level can also be very useful weapons that have the advantage of being able to monitor longitudinally the clinical picture, something that real-time PCR/nasopharyngeal swab is not able to do and that CT can only pursue with significant radiation exposure A lesson learned in the early phase of the COVID-19 pandemic suggests quitting and starting again with targeted imaging and blood vascular biomarkers


title: Enhanced Accumulation of Coronavirus Defective Interfering RNA from Expressed Negative-Strand Transcripts by Coexpressed Positive-Strand RNA Transcripts

text: Abstract Expression of negative-strand murine coronavirus mouse hepatitis virus (MHV) defective interfering (DI) RNA transcripts in MHV-infected cells results in the accumulation of positive-strand DI RNAs (M. Joo et al., 1996, J. Virol. 70, 5769–5776). However, the expressed negative-strand DI RNA transcripts are poor templates for positive-strand DI RNA synthesis. The present study demonstrated that DI RNA accumulation from the expressed negative-strand DI RNA transcripts in MHV-infected cells was enhanced by the coexpression of complementary RNA transcripts that correspond to the 5′ region of positive-strand DI RNA. The positive-strand RNA transcripts corresponding to the 5′ end-most 0.7–2.0 kb DI RNA had a similar enhancement effect. The coexpressed positive-strand RNA transcripts lacking the leader sequence or those containing only the leader sequence failed to demonstrate this enhancement effect, demonstrating that the presence of the leader sequence in the coexpressed positive-strand RNA transcripts was necessary, but not sufficient, for the enhancement of DI RNA accumulation from the coexpressed negative-strand DI RNA transcripts. Negative-strand DI RNA transcripts that were coexpressed with the partial-length positive-strand RNA transcripts were no more stable than those expressed alone, suggesting that a higher stability of the expressed negative-strand RNA transcripts was an unlikely reason for the higher DI RNA accumulation in cells coexpressing two complementary DI RNA transcripts. Sequence analyses unexpectedly demonstrated that the leader sequence of the majority of accumulated DI RNAs switched to helper virus derived leader sequence, suggesting that enhancement of DI RNA accumulation was mediated by the efficient utilization of helper virus derived leader sequence for DI RNA synthesis. Furthermore, our data suggested that this leader switching, a type of homologous RNA–RNA recombination, occurred during positive-strand DI RNA synthesis and that MHV positive-strand RNA synthesis mechanism may have a preference toward recognizing double-stranded RNA structures over single-stranded negative-strand RNA to produce positive-strand DI RNAs.


title: Nurses reports of actual work hours and preferred work hours per shift among frontline nurses during coronavirus disease 2019 (COVID-19) epidemic: A cross-sectional survey

text: Abstract Background A novel coronavirus disease that emerged in China in December 2019 (COVID-19) has rapidly spread to all over the world, leading to 823 626 people diagnosed and 40 598 deaths globally as of April 1, 2020. Nurses are providing care to patients with COVID-19 who require hospitalization. To ensure adequate response capacity and to maintain the health of nurses at risk of infection, it is important to analyse the actual work hours and the nurses reported preferred work hours per shift among frontline nurses. Objective To analyse the actual work hours and preferred work hours per shift of nurses reports among frontline nurses fighting the COVID-19 epidemic and to explore the influencing factors on the nurses reported preferred work hours. Design Cross-sectional survey Setting(s) This study was conducted in 10 designated hospitals providing treatments to patients with COVID-19 in China. Participants Nurses providing care to patients with COVID-19 in designated hospitals in China. Methods A self-designed questionnaire with open-ended questions was used to assess frontline nurses caring for COVID-19 cases in 10 designated hospitals. Quantitative and qualitative methods were used to analyse the actual work hours, the nurses reported preferred work hours and factors influencing nurses reported preferred work hours among the frontline nurses. Results A total of 109 nurses responded to the survey. The actual work hours per shift among frontline nurses were exceeded the nurses reported preferred work hours [Median (interquartile range): 5.00(2.00) h vs 4.00 (2.00)h; Minmum-Maxmum: 4-12 h vs 4-8 h], and 60.55% (66/109) of the nurses regarded 4 h as the preferred number of work hours per shift. Five key themes associated with the influencing factors emerged, including circumstances, personal preventable equipment, the physical and emotional needs of nurse, the safety needs of nurse and work intensity. Conclusions These findings suggest that there is a gap between the actual work hours and the nurses reported preferred work hours among frontline nurses in different units and different posts. The main influencing factors were circumstances, personal preventable equipment, the physical and emotional needs of nurse, the safety needs of nurse and work intensity.


title: High prevalence and diversity of bovine astroviruses in the faeces of healthy and diarrhoeic calves in South West Scotland

text: Abstract Astroviruses (AstV) are single-stranded, positive-sense RNA viruses and one of the major causes of infant diarrhoea worldwide. Diarrhoea is a common and important cause of morbidity and mortality in calves; therefore, we investigated whether the presence of AstV is associated with calf diarrhoea. We identified diverse AstV lineages from faecal samples of both healthy and diarrhoeic calves and healthy adult cattle in South West Scotland. AstV was common in calves (present in 74% (85/115) of samples) but uncommon in adult cattle (present in 15% (3/20) of samples). No association was found between the presence of AstV and calf diarrhoea or the presence of a specific AstV lineage and calf diarrhoea. AstV was strongly associated with the presence of rotavirus Group A (RVA), and a protective effect of age was evident for both AstV and RVA. Co-infections with multiple AstV lineages were detected in several calves and serial infection with different viruses could also be seen by longitudinal sampling of individuals. In summary, our study found genotypically diverse AstV in the faeces of calves in South West Scotland. However, no association was identified between AstV and calf diarrhoea, which suggests the virus does not play a primary role in the aetiology of calf diarrhoea in the group studied.


docid: kcfxwjjn

title: Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy

text: BACKGROUND: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. METHODS: In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R. RESULTS: The TLR7 rs179008A > T (p < 0.001) polymorphism was associated while the TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p < 0.001) and TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations. CONCLUSIONS: Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.


title: Will COVID-19 affect food supply in distribution centers of Brazilian regions affected by the pandemic?

text: BACKGROUND: Currently, there is great concern about the consequences of COVID-19 on health and also on food supply globally. Ceasas are important food distribution centers in Brazil that have great economic importance in Brazilian agribusiness. SCOPE AND APPROACH: In this work, the price of fruits and vegetables sold in four Ceasas in different regions affected by COVID-19 in the first quarter of 2020 were evaluated, with the aim of verifying the possible effects of the pandemic on food supply chains. Data were collected from the institutions' websites and subjected to analysis of variance and Tukey's test (p ≤ 0.05), principal component analysis and Cluster analysis (Euclidean distance). Key findings and conclusions: The regions affected by COVID-19 showed great variations in the prices of products sold in the studied Ceasas. Statistical analysis showed that food prices were dependent on the regions and the period in which they were traded. In general, the month of March proved to have the greatest impact on the consumer's pocket. The strengthening of Ceasas as platforms for supplying food from short supply chains is essential to guarantee internal food security during crises such as that caused by the coronavirus.


title: First International Proficiency Study on West Nile Virus Molecular Detection

text: Background: West Nile virus (WNV) molecular detection is being conducted by a growing number of laboratories, but the degree of proficiency may vary between them. External quality control is needed. Methods: We have conducted an international quality assurance study on WNV molecular detection. Participating laboratories tested noninfectious samples inactivated by heat and gamma irradiation. Participants received 7 coded lyophilized samples containing WNV of genetic lineages 1a, 1b, and 2 at 2600 to 18 000 000 RNA copies/mL, 3 samples containing heterologous flaviviruses, and 2 negative samples. Results: Thirty laboratories participated. The average laboratory achieved 50% detection probability from 7762 copies/mL onward (probit analysis; 95% CI = 1174–24547 copies/mL). Lineages 1a and 1b were detected with equal efficiencies, but the lineage 2 strain (Ug37) was detected at significantly lower rates. Only 27% of participants were able to detect the 6 samples containing ≥1.8 × 10(4) copies/mL. Three laboratories generated false-positive results in negative samples. Six of 30 laboratories reported correct strain identification in 3 samples containing non-WNV flaviviruses. We observed a significant positive correlation between the capability of detecting non-WNV flaviviruses and detecting WNV lineage 2. Conclusions: Most participants showed good performance in detecting lineage 1 WNV, the predominant virus in the Northern Hemisphere. The inability of some laboratories to detect even highly concentrated lineage 2 WNV downgraded the overall outcome. The lineage 2 material received through this study will provide laboratories with the necessary template for improving their assays. Such material is otherwise hard to obtain.


title: Pathogenicity of experimental infection with ‘pneumotropic’ porcine coronavirus

text: Virus localisation and lesions were studied in 14 one-week-old piglets following combined intranasal-oral inoculation with a British isolate of ‘pneumotropic’ porcine coronavirus (pcv) and were compared with the effects of transmissible gastroenteritis virus (tgev) infection in five piglets. Unlike TGEV-infected piglets, all pcv-inoculated piglets remained clinically healthy. Seroconversion was detected at seven days after inoculation. Mild bronchointerstitial pneumonia involving terminal airways was consistently present at two days after infection and thereafter. Both pcv and tgev infected bronchiolar epithelium and alveolar macrophages but, unlike tgev, replication by pcv in villous enterocytes was limited and did not cause villous atrophy.


title: Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea

text: We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.


title: A survey of feline leukaemia virus antigenaemia among cats in eastern Austria: a retrospective analysis of serum samples routinely tested between 1996 and 2011

text: OBJECTIVES: The aim of this retrospective analysis was to determine the seroprevalence of feline leukaemia virus (FeLV) antigenaemia among owned cats in Vienna and the surrounding area. METHODS: Samples were tested between 1996 and 2011 by the Department of Clinical Virology at the University of Veterinary Medicine, Vienna, Austria. All samples were sent to the university as part of routine diagnostic procedures, either to determine infection in clinically symptomatic individuals or to rule out infection prior to vaccination. To allow for statistical comparison, samples analysed between 2008 and 2011 were pooled into one population (n = 444) and evaluated against samples tested in 1996 (n = 840). Furthermore, analyses of subgroups were undertaken to determine the effect of sex and age on the prevalence of FeLV antigenaemia. RESULTS: With respect to the samples tested at the University of Veterinary Medicine in Vienna, it was determined that the level of FeLV antigenaemia in eastern Austria between 1996 and 2011 was 5.6%. The proportion of FeLV antigenaemic cats was highly variable and has not fallen significantly over this period, despite advances in vaccination, and the education of pet owners and animal welfare charities. CONCLUSIONS AND RELEVANCE: This study confirms the importance of continued and regular vaccination against FeLV among Austrian cats, particularly those allowed access to the outdoors. Within the remit of this retrospective study, it was not possible to follow-up results of repeat testing or of other assays (PCR) of individual cats. As a result of this, no conclusions can be drawn as to the possibility of transient antigenaemic cats or false-positive enzyme-linked immunosorbent assay results.


title: COVID-19 Reinfection: Myth or Truth?

text: The novel coronavirus disease (COVID-19) has posed a large problem to this world and has exposed the skeleton of healthcare system all over. There have been reports of patients getting reinfected with COVID-19 as they tested positive for the virus again after discharge. We try to address the issue of this reinfection and want to clarify whether this entity actually exists or is it just a myth.


COVID‐19 pandemic: implications on the surgical treatment of gastrointestinal and hepatopancreatobiliary tumours in Europe


title: Involuntary ambulatory triage during the COVID-19 pandemic – A neurosurgical perspective

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to health-care systems around the world. As approximately one-third of the world´s population is living under “lockdown” conditions, medical resources are being reallocated and hospital admissions are limited to emergencies. We examined the decision-making impact of these actions and their effects on access to hospital treatment in patients with neurosurgical conditions. METHODS: This retrospective cohort study analyzes hospital admissions of two major neurosurgical services in Germany during the nationwide lockdown period (March 16(th) to April 16(th), 2020). Spinal or cranial conditions requiring immediate hospital admission and treatment constituted emergencies. RESULTS: A total of 243 in-patients were treated between March 16(th) and April 16(th) 2020 (122 patients at the University Medical Center Mainz, 121 patients at the University Medical Center Göttingen). Of these, 38.0±16% qualified as emergency admission. Another 1,688 admissions were reviewed during the same periods in 2018 and 2019, providing a frame of reference. Overall, emergency admissions declined by 44.7±0.7% during lockdown. Admissions for cranial emergencies fell by 48.1±4.44%, spinal emergencies by 30.9±14.6%. CONCLUSION: Above findings indicate that in addition to postponing elective procedures, emergency admissions were dramatically curtailed during the COVID-19 lockdown. As this surely is unexpected and unintended, reasons are undoubtedly complex. As consequences in morbidity and mortality are still unpredictable, efforts should be made to accommodate all patients in need of hospital access going forward.


Comment to Döhla et al., Rapid point-of-care testing for SARS-CoV- 2 in a community screening setting shows low sensitivity


title: Interfering with disease: opportunities and roadblocks to harnessing RNA interference

text: Abstract RNA interference (RNAi) is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. Short double-stranded RNAs, known as small interfering RNAs (siRNA), are incorporated into an RNA-induced silencing complex that directs degradation of RNA containing a homologous sequence. RNAi has been shown to work in mammalian cells, and can inhibit viral infection and control tumor cell growth in vitro. Recently, it has been shown that intravenous injection of siRNA or of plasmids expressing sequences processed to siRNA can protect mice from autoimmune and viral hepatitis. RNAi could provide an exciting new therapeutic modality for treating infection, cancer, neurodegenerative disease and other illnesses.


title: Birth seasonality studies in a large Prader–Willi syndrome cohort

text: Prader‐Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11‐q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11‐q13 deletion seen in PWS. Certain occupations such as hydrocarbon‐exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11‐q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation.


title: Controlled fluorescence quenching by antibody-conjugated graphene oxide to measure tau protein

text: We report an ultrasensitive immunoassay for tau protein—a key marker of Alzheimer's disease. This sensing platform relies on graphene oxide (GO) surfaces conjugated with anti-human tau antibody to provide quantitative binding sites for the tau protein. The GO quenches standard fluorescein isothiocyanate labelled tau (tau-FITC) when tau protein and tau-FITC are both present and compete for the binding sites. This change in fluorescence signal can be used to quantitate tau protein. In contrast with traditional enzyme-linked immunosorbent assay (ELISA), our method does not require enzyme-linked secondary antibodies for protein recognition nor does it require an enzyme substrate for optical signal generation. This requires fewer reagents and has less systematic error than the antigen–antibody recognition steps in ELISA. Our method has a tau protein detection limit of 0.14 pmol ml(−1) in buffer. This approach could be developed into a promising biosensor for the detection of tau protein and may be useful in the clinical diagnosis of tau-induced neurodegeneration syndromes.


Rethinking the role of senior medical students in the COVID‐19 response


title: An alternative workflow for molecular detection of SARS-CoV-2 – escape from the NA extraction kit-shortage, Copenhagen, Denmark, March 2020

text: The World Health Organization has declared COVID-19 caused by the newly discovered SARS-CoV-2 a pandemic. Due to growing demand for reagents and/or kits to extract SARS-CoV-2 RNA for subsequent RT-qPCR diagnostics, there is a worldwide risk of shortages. With a detection sensitivity of 97.4% (95% CI: 86.2–99.9%), we describe a simple, fast, alternative workflow for molecular detection of SARS-CoV-2, where samples are simply heat-processed for 5 min at 98 °C before a commonly-used RT-qPCR procedure.


title: Novel Coronavirus 2019 Transmission Risk in Educational Settings

text: Transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools is unknown. Our investigations, especially in preschools, could not detect SARS-CoV-2 transmission despite screening of symptomatic and asymptomatic children. The data suggest that children are not the primary drivers of SARS-CoV-2 transmission in schools and could help inform exit strategies for lifting of lockdowns.


title: Effect van influenzavaccinatie op het aantal sterfgevallen tijdens perioden van verhoogde circulatie van influenzavirus in de populatie

text: Het probleem van influenza is dat het een syndroom is dat niet specifiek is voor influenza, omdat meerdere micro-organismen influenza-achtige ziektebeelden kunnen veroorzaken: coronavirus, influenza A en B, para-influenza, rhinovirussen en het respiratoir syncytiaal virus. Voorts is de mortaliteit als hard eindpunt van influenza gering zodat een vaccinatieeffect niet gemakkelijk aantoonbaar is. Toch wil men gaarne zekerheid hebben dat de gelden, aangewend om influenza te voorkomen, goed besteed zijn. Daarom hebben Armstrong et al. op een andere manier dan gebruikelijk naar het effect van influenzavaccinatie gekeken, namelijk door de toename van de sterfte die niet optreedt bij gevaccineerden, te vergelijken met die bij niet-gevaccineerden gedurende perioden waarin er veel influenzavirus circuleert en in perioden waarin dat niet zo is. Het onderzoek omvatte 24.535 mensen van 75 jaar of ouder in 73 huisartspraktijken en vond plaats van januari 1996 tot augustus 2000.


title: Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells

text: Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.


title: Complete Genome Sequence of a Novel Strain of Infectious Bronchitis Virus, Isolated from Chickens in China in 2016

text: An avian infectious bronchitis virus (IBV) was detected from trachea swabs of chickens in Hubei province, China, in 2016. The complete genome of the IBV strain, CK/CH/HB/2016, was characterized and analyzed to better understand IBV epidemiology in China.


Reflections on the quality of health care after the SARS-CoV-2 pandemic


title: Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein

text: Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses. In this study, we show strong evidence that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus, specifically interacts with Nmi. This interaction was identified through a yeast two-hybrid screen and co-immunoprecipitation in human cells. We observed that Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23 binding of Nmi disrupts the interaction of Nmi with STAT1. In cells overexpressing UL23, we observed (a) significantly reduced levels of Nmi and STAT1 in the nuclei, the sites where these proteins act to induce transcription of IFN-γ stimulated genes, and (b) decreased levels of the induction of the transcription of IFN-γ stimulated genes. UL23-deficient HCMV mutants induced higher transcription of IFN-γ stimulated genes and exhibited lower titers than parental and control revertant viruses expressing functional UL23 in IFN-γ treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit nuclear translocation of Nmi and its associated protein STAT1, leading to a decrease of IFN-γ induced responses and an increase of viral resistance to IFN-γ. Our results further highlight the roles of UL23-Nmi interactions in facilitating viral immune escape from IFN-γ responses and enhancing viral resistance to IFN antiviral effects.


Deceases in Acute Heart Failure Hospitalizations during COVID‐19


docid: ekfuspva

title: Gastrointestinal: Bowel ischemia in a suspected coronavirus disease (COVID‐19) patient


title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation

text: BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality. METHODS: Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality. RESULTS: Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.


title: Cotton-Tipped Plastic Swabs for SARS-CoV-2 RT-qPCR Diagnosis to Prevent Supply Shortages

text: CDC and WHO guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis only recommend synthetic fiber swabs for nasopharyngeal (NP) sampling. We show that cotton-tipped plastic swabs do not inhibit PCR and have equivalent performance to rayon swabs. Cotton-tipped plastic swabs are massively produced worldwide and would prevent swab supply shortages under the current high SARS-CoV-2 testing demands, particularly in developing countries.


title: Biomedical Research Goes Viral: Dangers and Opportunities

text: Researchers around the globe have been mounting, accelerating and redeploying efforts across disciplines and organizations to tackle the SARS CoV-2 outbreak. However, humankind continues to be afflicted by numerous other devastating diseases in increasing numbers. Here, we outline considerations and opportunities toward striking a good balance between maintaining and redefining research priorities.


title: CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa

text: In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) colonizes the lungs, leading to chronic inflammation of the bronchial epithelium. ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) mRNA is differentially expressed in primary human airway epithelial cells from bronchi (hAECBs) from patients with CF and healthy patients at baseline and upon infection with Pa. CHAC1 degrades glutathione and is associated with ER stress and apoptosis pathways. In this study, we examined the roles of CHAC1 in the inflammatory response and apoptosis in lung epithelial cells. First, we confirmed by reverse transcription quantitative polymerase chain reaction that CHAC1 mRNA was overexpressed in hAECBs from patients without CF compared with the expression in hAECBs from patients with CF upon Pa (PAK strain) infection. Moreover, the Pa virulence factors LPS and flagellin were shown to induce CHAC1 expression in cells from patients without CF. Using NCI-H292 lung epithelial cells, we found that LPS-induced CHAC1 mRNA expression was PERK-independent and involved ATF4. Additionally, using CHAC1 small interfering RNA, we showed that reduced CHAC1 expression in the context of LPS and flagellin stimulation was associated with modulation of inflammatory markers and alteration of NF-κB signaling. Finally, we showed that Pa was not able to induce apoptosis in NCI-H292 cells. Our results suggest that CHAC1 is involved in the regulation of inflammation in bronchial cells during Pa infection and may explain the excessive inflammation present in the respiratory tracts of patients with CF.


Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases


title: Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus

text: The recent emergence and re-emergence of alphaviruses, in particular the chikungunya virus (CHIKV), in numerous countries has invoked a worldwide threat to human health, while simultaneously generating an economic burden on affected countries. There are currently no vaccines or effective drugs available for the treatment of the CHIKV, and with few lead compounds reported, the vital medicinal chemistry is significantly more challenging. This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, and molecular dynamics simulations, as well as work done to evaluate and confirm the active site of nsP3. Virtual screening was carried out based on blind docking as well as focused docking, using the database of 1541 compounds from NCI Diversity Set II, to identify hit compounds for nsP3. The top hit compounds were further subjected to molecular dynamic simulations, yielding a greater understanding of the dynamic behavior of nsP3 and its complexes with various ligands, concurrently confirming the outcomes of docking, and establishing in silico lead compounds which target the CHIKV nsP3 enzyme. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-014-2216-6) contains supplementary material, which is available to authorized users.


Comment on ‘Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic?’


title: eHealth – Smart Devices revolutionieren die Kardiologie

text: BACKGROUND: The use of smart devices such as smartphones and smartwatches in cardiology continues to significantly increase. The widespread use is also promoted by patients and the industry. OBJECTIVES: The goal is to assess different opportunities of smart devices in cardiology. MATERIALS AND METHODS: A selected review of the literature was carried out. Scientific and clinical studies regarding possible applications of these devices were evaluated. RESULTS: The use of smartphones in Germany is among the highest worldwide. This allows very broad use of this technology in general and in the medical field. There are various potential applications ranging from a reference source over clinical decision support to biosignal sensing. Particularly, the combination of biosignal collection and interpretation by artificial intelligence could lead to a significant improvement of our diagnostic methods and precisely predict the course of various cardiovascular diseases. CONCLUSIONS: Smart devices are already increasingly used in daily clinical practice. Due to the numerous technical opportunities, the use of these devices will further spread and, most probably, will transform cardiology.


title: Cost-effectiveness of transfusion of platelet components prepared with pathogen inactivation treatment in the United States

text: Abstract Background: The Intercept Blood System (IBS) for platelets has been developed to reduce pathogen transmission risks during transfusions. Objective: This study was a comprehensive economic analysis of the cost-effectiveness of using the IBS for single-donor apheresis platelets (AP) and random-donor pooled platelet concentrates (PC) versus AP and PC without the IBS in the United States in patient populations in which platelets are commonly transfused. Methods: All data used in this analysis were summarized from existing published sources (primarily indexed in MEDLINE) and data on file at Baxter Healthcare Corporation (Chicago, Illinois) and Cerus Corporation (Concord, California). A literature-based decision-analytic model was developed to assess the economic costs and clinical outcomes associated with the use of AP and PC treated with the IBS for several conditions and procedures that account for a considerable proportion of the platelet usage in the United States: acute lymphocytic leukemia, non-Hodgkin's lymphoma, coronary artery bypass graft, and hip arthroplasty Risks of infection with HIV, hepatitis C virus (HCV), hepatitis B virus, human T-cell lymphotropic virus type 1, or bacterial agents were incorporated into the model. Possible benefits of reduction of the risk of emerging HCV like pathogens and elimination of the need for gamma irradiation were explored in sensitivity analyses. Results: The incremental cost per quality-adjusted life-year gained by using AP + IBS versus untreated AP ranged from $1,308,833 to $4,451,650 (without bacterial testing) and $4,759,401 to $22,968,066 (with bacterial testing). Corresponding figures for PC + IBS versus untreated PC ranged from $457,586 to $1,816,060. Inclusion of emerging HCV like virus and the elimination of the need for gamma irradiation improved the cost-effectiveness to a range of $177,695 to $1,058,127 for AP without bacterial testing, $176,572 to $1,330,703 for AP with bacterial testing, and $22,888 to $153,564 for PC. The model was most likely to be affected by mortality from bacterial contamination, IBS effect on platelet utilization, and the inclusion of potential benefits (ie, gamma irradiation and/or emergent HCVlike virus). The model was relatively insensitive to changes in the IBS price and viral transmission risks. Conclusions: The cost-effectiveness of pathogen inactivation via the IBS for platelets is comparable to that of other accepted blood safety interventions (eg, nucleic acid amplification technology). The IBS for platelets may be considered a desirable strategy to increase the safety of platelet transfusions and a potential insurance against the threat of emerging pathogens.


title: Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong

text: Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.


docid: heysgffz

title: COVID-19 Outbreak in Malaysia: Actions Taken by the Malaysian Government

text: AIM AND BACKGROUND: COVID-19, a novel pneumonia disease originated from Wuhan, was confirmed by World Health Organization on 12th January 2020 before becoming an outbreak in all countries. OUTBREAK SITUATION: A stringent screening process in all airports had been enforced after the first case outside China was reported in Thailand. Up to 14th April 2020, Malaysia reported two waves of COVID-19 cases, which the first wave was successfully ended in less than two months. In early March 2020, the second wave arose with worrying situations. ACTIONS TAKEN: Malaysia government enforced the Movement Control Order starting from 18th March 2020 to seriously break the chain of COVID-19. Media actively spread the hashtag #stayhome. Non-governmental organizations including prison inmates were the earliest to sew personal protective equipment to frontliners. Various organizations hosted fund raising to provide essentials mainly to hospitals. Provisional hospital was set up, collaborations with healthcare service providers were granted while additional laboratories were assigned in enhancing the proficiency of Ministry of Health. ECONOMIC DOWNTURN: Initial financial stimulus amount RM 20.0 billion was released in February 2020 before the highlighted PRIHATIN package, amount RM 250 billion was announced. The PRIHATIN package was an all-inclusive support from the government to society in various backgrounds from students, families to business owners.


title: RE-MuSiC: a tool for multiple sequence alignment with regular expression constraints

text: RE-MuSiC is a web-based multiple sequence alignment tool that can incorporate biological knowledge about structure, function, or conserved patterns regarding the sequences of interest. It accepts amino acid or nucleic acid sequences and a set of constraints as inputs. The constraints are pattern descriptions, instead of exact positions of fragments to be aligned together. The output is an alignment where for each pattern (constraint), an occurrence on each sequence can be found aligned together with those on the other sequences, in a manner that the overall alignment is optimized. Its predecessor, MuSiC, has been found useful by researchers since its release in 2004. However, it is noticed in applications that the pattern formulation adopted in MuSiC, namely, plain strings allowing mismatches, is not expressive and flexible enough. The constraint formulation adopted in RE-MuSiC is therefore enhanced to be regular expressions, which is convenient in expressing many biologically significant patterns like those collected in the PROSITE database, or structural consensuses that often involve variable ranges between conserved parts. Experiments demonstrate that RE-MuSiC can be used to help predict important residues and locate phylogenetically conserved structural elements. RE-MuSiC is available on-line at http://140.113.239.131/RE-MUSIC.


title: SARS Clinical Features, United States, 2003

text: We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.


The international response to the COVID-19 pandemic in radiation oncology


title: A multiple center clinical evaluation of an ultra-fast single-tube assay for SARS-CoV-2 RNA

text: OBJECTIVES: To evaluate the performance of an ultra-fast single-tube nucleic acid isothermal amplification detection assay for SARS-CoV-2 RNA using clinical samples from multiple centers. METHODS: A reverse transcription recombinase-aided amplification (RT-RAA) assay for SARS-CoV-2 was conducted within 15minutesat39°C with portable instruments after addition of extracted RNA. The clinical performance of RT-RAA assay was evaluated using 947 clinical samples from five institutions in four regions of China, and the approved commercial real-time fluorescent RT-PCR (qRT-PCR) kits were used for parallel detection. The sensitivity and specificity of RT-RAA were compared and analyzed. RESULTS: The RT-RAA test results of 926 samples were consistent with those of qRT-PCR (330 were positive, 596 were negative) and 21 were inconsistent. The sensitivity and specificity of RT-RAA was 97.63% [330/338, 95% confidence interval (CI): 95.21 to 98.90] and 97.87% (596/609, 95% CI: 96.28 to 98.81), respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 96.21% (330/343, 95% CI: 93.45 to 97.88), and 98.68% (596/604, 95% CI: 97.30 to 99.38), respectively. The total coincidence rate was 97.78% (926/947, 95% CI: 96.80 to 98.70) and the Kappa was 0.952 (P <0.05). CONCLUSION: With comparable sensitivity and specificity to the commercial qRT-PCR kits, RT-RAA assay for SARS-CoV-2 exhibited distinctive advantages of simplicity and rapidity in terms of operation and turn-around time.


docid: jkjkkjrf

title: The guanine nucleotide exchange factor GBF1 participates in rotavirus replication

text: Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference, or inhibiting its activity by treatment with Brefeldin A (BFA) or Golgicide A (GCA) significantly reduce the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly since in the presence of either BFA or GCA the assembly of infectious mature triple-layered virions was significantly prevented and only doubled layered-particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface VP7, a step required for its incorporation into virus particles. Although a post-translational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking-down its expression reduces VP7 trimerizarion. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when co-transfected with NSP4. Rotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite the significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for the COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4, and the assembly of the virus surface proteins VP7 and VP4.


title: Neumonía adquirida en la comunidad en pacientes adultos con síndrome de Down. Presentación de tres casos clínicos y revisión de la literatura

text: Resumen John Langdon Down fue el primero en describir el cuadro clínico de esta alteración genética caracterizada por trisomía del cromosoma 21, también conocida como síndrome de Down (SD). La frecuente aparición de infecciones respiratorias en el SD se atribuye a numerosas anomalías estructurales y funcionales, a la presencia de malformaciones congénitas cardíacas y a déficits de IgG. Se presentan tres casos clínicos de pacientes adultos con SD que padecieron una neumonía adquirida en la comunidad y se realiza una revisión bibliográfica considerando los aspectos epidemiológicos, la prevalencia, el cuadro clínico, los datos de laboratorio y los radiológicos, la morbimortalidad, la evolución y la importancia de la prevención. Estos pacientes pueden presentar síntomas de infección aguda del aparato respiratorio bajo, como fiebre alta, tos con o sin expectoración, dolor torácico por irritación pleural, disnea, fatiga, mialgias, así como otros síntomas atípicos. La radiografía de tórax puede mostrar un foco de condensación inflamatoria en un pulmón, o un infiltrado alveolointersticial bilateral. La analítica de sangre puede mostrar leucocitosis, aumento de la proteína C reactiva, deficiencia de IgG y de los linfocitos CD4+. Los pacientes con SD son altamente susceptibles a padecer infecciones respiratorias del tracto superior como del inferior. Los médicos deben tener especial precaución ante la presencia de síntomas respiratorios en estos pacientes, ya que en muchas ocasiones pueden desarrollar neumonías y bronconeumonías que se presentan de forma atípica y con complicaciones que se acompañan de alta mortalidad. Abstract John Langdon Down first described this genetic disorder known today as Down syndrome (DS), due to a trisomy of chromosome 21. The frequent appearance of respiratory infections in DS is attributed to structural and functional anomalies of the respiratory system, the presence of congenital heart malformations and IgG deficits. We present three clinical cases of adult DS patients with community-acquired pneumonia, and a review of the literature regarding: epidemiology, prevalence, symptomatology, laboratory and radiographic findings, morbidity, mortality, clinical evolution and the importance of prevention of pneumonia in DS patients. These patients presented symptoms of acute infection of the lower respiratory tract: high fever, scanty productive cough with or without sputum, pleuritic chest pain, dyspnea, fatigue, myalgia, and other atypical symptoms. Chest radiography showed focal inflammatory condensation in the affected lung and bilateral alveolo-interstitial infiltrate. Laboratory tests showed increased values of leukocytes and C-reactive protein, deficiency of IgG and low lymphocyte CD4+. Patients with DS are highly susceptible to lower and higher respiratory tract infection. Community physicians should take exceptional precautions on detecting respiratory symptoms in these patients, since they may result in pneumonia and bronchopneumonia. Presentation may be atypical and the complications may even lead to mortality.


title: Global research trends in West Nile virus from 1943 to 2016: a bibliometric analysis

text: BACKGROUND: West Nile virus (WNV) is an emerging infectious disease which is most commonly transmitted to humans through mosquito, and is considered a major public-health problem worldwide. The aim of the current study is to bibliometrically analyze the quantity and quality of publications indexed in Scopus from different countries to reveal the characteristics of global research output regarding WNV. METHODS: This study is a bibliometric analysis based on the Scopus database. This study focused on identifying WNV publication trends with regard to publication year, publication type, prolific countries, language of publication, as well as, prolific journals, citations, and collaboration patterns. RESULTS: A total of 4729 publications were considered in this study, which were published between 1943 and 2016. The annual quantity of literature published before 2000 followed a low rate of research growth; while the quantity of publications after 2000 were published in a stage of rapid development. The country with the greatest number of publications in WNV research field was the USA with 2304 (48.7%) publications, followed by France with 224 (4.7%) publications, and Canada with 222 (4.7%) publications. Contributions from low- and middle-income countries (LMIC) were considerably small, that is, (n = 519 publications; 11%). All publications related to WNV achieved h-index of 140 and were cited 124,222 times. The median [interquartile range] number of citations per article thus amounts to 9 [2-28]. The USA had the highest h-index of 131. Emerging Infectious Diseases is the most productive journal with 227 articles, followed by Journal of Virology with 162 publications. The result designated that Centers for Disease Control and Prevention was ranked the first in terms of publication output, followed by National Center for Emerging and Zoonotic Infectious Diseases. CONCLUSIONS: There is an obvious trend of WNV research after 2000, and countries with high income have more contributions in WNV research field. The research output is low among LMIC. The USA produced the largest number of publications. The Centers for Disease Control and Prevention obtained the leading position of the institutions in terms of publication output. In general, this study not only presents a full view of global WNV research, but also can contribute for future further research in this field.


title: Review and comparison between the Wells–Riley and dose‐response approaches to risk assessment of infectious respiratory diseases

text: Abstract Infection risk assessment is very useful in understanding the transmission dynamics of infectious diseases and in predicting the risk of these diseases to the public. Quantitative infection risk assessment can provide quantitative analysis of disease transmission and the effectiveness of infection control measures. The Wells–Riley model has been extensively used for quantitative infection risk assessment of respiratory infectious diseases in indoor premises. Some newer studies have also proposed the use of dose‐response models for such purpose. This study reviews and compares these two approaches to infection risk assessment of respiratory infectious diseases. The Wells–Riley model allows quick assessment and does not require interspecies extrapolation of infectivity. Dose‐response models can consider other disease transmission routes in addition to airborne route and can calculate the infectious source strength of an outbreak in terms of the quantity of the pathogen rather than a hypothetical unit. Spatial distribution of airborne pathogens is one of the most important factors in infection risk assessment of respiratory disease. Respiratory deposition of aerosol induces heterogeneous infectivity of intake pathogens and randomness on the intake dose, which are not being well accounted for in current risk models. Some suggestions for further development of the risk assessment models are proposed. PRACTICAL IMPLICATIONS: This review article summarizes the strengths and limitations of the Wells–Riley and the dose‐response models for risk assessment of respiratory diseases. Even with many efforts by various investigators to develop and modify the risk assessment models, some limitations still persist. This review serves as a reference for further development of infection risk assessment models of respiratory diseases. The Wells–Riley model and dose‐response model offer specific advantages. Risk assessors can select the approach that is suitable to their particular conditions to perform risk assessment.


title: Medical residents’ attitudes and emotions related to Middle East respiratory syndrome in Saudi Arabia: A cross-sectional study

text: OBJECTIVES: To determine medical residents’ emotions, attitudes, and knowledge related to Middle East respiratory syndrome (MERS) outbreaks. METHODS: In this is a cross sectional study, self-administered questionnaires were distributed and collected before resident education activities in 4 tertiary hospitals in Riyadh, Kingdom of Saudi Arabia, between November 2015 and January 2016. The questionnaire included questions related to residents’ demographic data and their emotions, attitudes, and knowledge related to an MERS outbreak. RESULTS: Of the 228 participants analyzed, 85.5% believed their work put them at risk of infection, and two-thirds believed their family was exposed to a greater risk of infection. However, only 2.6% would change their job. Nearly half of the residents indicated that their hospital had a clear plan, and only 28% considered themselves not well prepared for an MERS outbreak. CONCLUSIONS: Our study highlights medical residents’ attitude and emotions related to MERS outbreaks. Residents’ concerns and emotions in relation to MERS should be considered in greater detail by hospital policymakers.


title: Virological surveillance of influenza-like illness in the community using PCR and serology

text: Abstract Background: Surveillance of winter respiratory viral illness has been carried out for nearly 30 years using a clinical diagnosis by general practitioners as part of the Scottish Sentinel General Practice (SSGP) network. Contemparaneous laboratory diagnosis has not been available previously. Objectives: To assess the proportion of influenza-like illness (ILI) attributable to influenza, respiratory syncytial virus (RSV) and picornavirus infection during the winter season. To compare the influenza PCR data with serology of paired blood samples. Study design: Combined nose and throat swabs, from patients with ILI attending 15 general practices across Scotland, were submitted to the laboratory in virus PCR sample solution (VPSS). The extracted nucleic acid was tested using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) assay. Serological analysis was performed on paired serum samples using complement fixation assays. The rate of influenza virus positivity was compared with reports of ILI obtained from the SSGP network. Results: Of 240 samples received at the laboratory, 132 (55%) were PCR positive for influenza A virus. There were nine (3.8%) picornavirus and three (1.2%) RSV PCR positives, two (0.8%) were dual influenza A/picornavirus infections. Ninety four (39.2%) were negative for all viruses tested. Results on paired sera from 89 patients showed a rising titre to influenza A in 48 of the 57 PCR positive samples (84.2%). One PCR negative patient displayed a significant rising titre to influenza A. Virological data paralleled the SSGP data but was available at least a week earlier. Conclusions: Influenza A infection was detected in the majority of patients with ILI; picornavirus infection was also shown to be an important cause of illness. PCR is a rapid and sensitive method for respiratory virus surveillance. Serology is slow, insensitive and difficult to interpret at low titres.


title: COVID‐19 in an HIV‐positive Kidney Transplant Recipient

text: We report a case of a 50‐year‐old male with a history of HIV and kidney transplant who presented with SARS‐CoV‐2. We also present a review of COVID‐19 cases in kidney transplant recipients.


title: Modular organization of SARS coronavirus nucleocapsid protein

text: The SARS-CoV nucleocapsid (N) protein is a major antigen in severe acute respiratory syndrome. It binds to the viral RNA genome and forms the ribonucleoprotein core. The SARS-CoV N protein has also been suggested to be involved in other important functions in the viral life cycle. Here we show that the N protein consists of two non-interacting structural domains, the N-terminal RNA-binding domain (RBD) (residues 45–181) and the C-terminal dimerization domain (residues 248–365) (DD), surrounded by flexible linkers. The C-terminal domain exists exclusively as a dimer in solution. The flexible linkers are intrinsically disordered and represent potential interaction sites with other protein and protein-RNA partners. Bioinformatics reveal that other coronavirus N proteins could share the same modular organization. This study provides information on the domain structure partition of SARS-CoV N protein and insights into the differing roles of structured and disordered regions in coronavirus nucleocapsid proteins.


title: Antibacterial performance of a novel photocatalytic-coated cordierite foam for use in air cleaners

text: Abstract A novel titanium dioxide-coated cordierite foam (TiO2/cordierite foam) was developed for use in air cleaners. By a simple impregnation procedure, TiO2 nanoparticles were immobilized firmly onto the surface of a cordierite foam substrate through high-temperature (500°C) calcination. The strong bactericidal performance of the fabricated foam was evaluated by a newly developed test method for complex three-dimensional through-pore structures. This method could trace 5–6log units of decrease in bacterial cell numbers in an air environment, thus meeting the criteria of both the JIS and ISO standard test methods. With 0.25mWcm−2 of UV-A irradiation for 24h, the bactericidal rate of the TiO2/cordierite foam exceeded 99.9% for five types of airborne or droplet-based infectious pathogens: Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Legionella pneumophila (L. pneumophila), Klebsiella pneumoniae (K. pneumoniae), and methicillin-resistant Staphylococcus aureus (MRSA). The results of repeat testing, where the same sample was used three times, revealed that the bactericidal rate for E. coli was maintained at 99.9% in the second and third use, indicating that the TiO2/cordierite foam possesses a long-term bactericidal action. The TiO2/cordierite foam also exhibited a high photocatalytic degradation capability on gaseous acetaldehyde, which is associated with sick building syndrome, and volatile organic compounds to generate CO2 and H2O. The results demonstrated that TiO2-coated cordierite foam has great potential for use in air-cleaning filters with not only high bactericidal performance to remove pathogens in the air and in droplets, but also strong decontaminating and deodorizing functionality.


title: A Reverse Genetics System for Cypovirus Based on a Bacmid Expressing T7 RNA Polymerase

text: Dendrolimus punctatus cypovirus (DpCPV), belonging to the genus Cypovirus within the family Reoviridae, is considered the most destructive pest of pine forests worldwide. DpCPV has a genome consisting of 10 linear double-stranded RNA segments. To establish a reverse genetics system, we cloned cDNAs encoding the 10 genomic segments of DpCPV into three reverse genetics vectors in which each segment was transcribed under the control of a T7 RNA polymerase promoter and terminator tagged with a hepatitis delta virus ribozyme sequence. We also constructed a vp80-knockout Autographa californica multiple nucleopolyhedrovirus bacmid to express a T7 RNA polymerase codon-optimized for Sf9 cells. Following transfection of Sf9 cells with the three vectors and the bacmid, occlusion bodies (OBs) with the typical morphology of cypovirus polyhedra were observed by optical microscopy. The rescue system was verified by incorporation of a HindIII restriction enzyme site null mutant of the 9th genomic segment. Furthermore, when we co-transfected Sf9 cells with the reverse genetics vectors, the bacmid, and an additional vector bearing an egfp gene flanked with the 5′ and 3′ untranslated regions of the 10th genomic segment, aggregated green fluorescence co-localizing with the OBs was observed. The rescued OBs were able to infect Spodopetra exigua larvae, although their infectivity was significantly lower than that of wild-type DpCPV. This reverse genetics system for DpCPV could be used to explore viral replication and pathogenesis and to facilitate the development of novel bio-insecticides and expression systems for exogenous proteins.


title: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease

text: The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.


title: Lung Cancer and the COVID-19 pandemic: Recommendations from the Brazilian Thoracic Oncology Group

text: New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.