title: H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination

text: A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.


title: Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations

text: Abstract Diamond-Blackfan anemia (DBA) is a rare congenital disorder presenting remarkable phenotypic overlap with other inherited bone marrow failure syndromes, making differential diagnosis challenging and its confirmation often reached with great delay. By whole exome sequencing, we unraveled the presence of pathogenic variants affecting genes already known to be involved in DBA pathogenesis (RPL5 and RPS19) in three patients with otherwise uncertain clinical diagnosis, and provided new insights on DBA genotype-phenotype correlations. Remarkably, the RPL5 c.482del frameshift mutation has never been reported before, whereas the RPS19 c.3G>T missense mutation, although previously described in a 2-month-old DBA patient without malformations and refractory to steroid therapy, was detected here in the mosaic state in different bodily tissues for the first time in DBA patients.


title: Evidence of Aujeszky’s disease in wild boar in Serbia

text: BACKGROUND: Aujeszky’s disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky’s disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky’s disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. RESULTS: Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky’s disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. CONCLUSIONS: This is the first demonstration of Aujeszky’s disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously.


SEVERE ASTHMA DURING THE COVID-19 PANDEMIC: CLINICAL OBSERVATIONS


title: Viral infections in patients with hematological malignancies

text: Viral infections remain one of the most frequent complications in patients with hematological malignancies, especially in those receiving an allogeneic stem cell transplantation. Viral infections result from reactivation of latent infection rather than from acquisition of new infection. Infections caused by herpes viruses, including cytomegalovirus and Epstein-Barr virus, respiratory viruses and hepatitis B virus are frequently associated with high morbidity and mortality in the immunocompromised host. Major advances have been made primarily by the availability of rapid diagnostic tests and the introduction of potent antiviral compounds into clinical practice.


title: Impact of porcine epidemic diarrhea on herd and individual Berkshire sow productivity

text: Abstract Porcine epidemic diarrhea (PED) is an emerging disease of pigs in several countries. In the present study, individual sow productivity of Berkshire sows exposed to PED virus at different stages of production was compared. On a commercial farrow-to-finish farm in Kagoshima Prefecture, Japan, the clinical presence of PED was observed in the farrowing barn on January 6, 2014, and all gilts and sows were immunized on January 9, except those in the farrowing barn. The sows were categorized into six groups based on the period in which they were exposed to PED virus: between days 0–30 (G1), 31–60 (G2), 61–90 (G3), or after 91 days of pregnancy (G4), during lactation (L), and after weaning (W). The control group was not exposed to PED during the period of PED outbreak. The study was based on 574 production records. The sows of the G4 and L groups had the fewest piglets weaned (4.8±0.4, and 4.0±0.3 pigs, respectively; P<0.05) and the greatest pre-weaning mortality (33.1±4.8%, and 39.7±4.1%, respectively; P<0.05). The number of piglets weaned and pre-weaning mortality, however, did not differ among the G1, G2, G3, and uninfected groups. The G4 and W groups had slightly lesser farrowing rates than the uninfected group (P<0.05), however, similar subsequent piglet litter performance as the uninfected group. In conclusion, the effect of PED on individual sow productivity differed with the production stage in which sows were exposed to PED virus.


title: Universal primers that amplify RNA from all three flavivirus subgroups

text: BACKGROUND: Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. RESULTS: Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5) coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. CONCLUSION: Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers.


title: Melamine and other food safety and health scares in China: Comparing households with and without young children

text: Abstract The purpose of this study was to determine whether household responses to melamine and other recent food safety and health scares in China in recent years differed between households that did or did not have young children (less than six years of age). A consumer survey was conducted in Hohhot, China in September 2009, one year after the melamine contamination of milk was disclosed to the public. Households with young children who were not being breast-fed reported that they had reduced milk consumption by at least 1/3 in the immediate aftermath of the melamine disclosure and 39% reported that they cut out milk consumption altogether. A significantly higher percentage of households with children reported being concerned with the effects of melamine in milk and two communicable diseases: SARS and H1N1 influenza than were those with no children. A significantly higher percentage of households with no young children were concerned with the effects of Trace Sudan in chicken, Clenbuterol in pork, chicken eggs with red yolks, and excess iodine in milk powder than were those with young children. All households that reduced consumption of fluid milk following news of the melamine contamination reported a much greater concern with most food safety and health scares than did households that did not reduce consumption of fluid milk. Survey data revealed that most consumers had a relatively low level of knowledge of the Food Safety Law that went into effect just over three months before this survey was conducted. Households with children also were significantly more concerned about melamine and two communicable diseases, SARS and H1N1 than were households without children.


title: Case-control study of the epidemiological and clinical features of human adenovirus 55 and human adenovirus 7 infection in children with acute lower respiratory tract infections in Beijing, China, 2008–2013

text: BACKGROUND: In adults, the emerging human adenovirus (HAdV) type 55 (HAdV-55) has been reported to cause more severe cases of adenovirus induced acute lower respiratory tract infections (ALRTIs) compared to other HAdV serotypes (HAdV-3, HAdV-7, HAdV-14). However, there is a dearth of comparative studies in children that address differences in the clinical epidemiological features between HAdV-55 and other HAdV serotypes that can also induce severe infection (such as HAdV-7). METHODS: We conducted a retrospective review of pediatric patients hospitalized at Beijing Children’s Hospital with ALRTI from April 2008 to December 2013 who had adenovirus detected from nasopharyngeal or throat samples by PCR. We further compared pediatric patients infected with HAdV-55 to those infected with HAdV-7 using a case-control methodology by matching each subject with HAdV-55 infection to 4 patients with HAdV-7 infection within 2 months of each HAdV-55 infection. Demographic, clinical, and etiological data were collected and analyzed. RESULTS: Over the five-year period, HAdV was detected in 194 children. Of these, 8 were HAdV-55 positive. Epidemiological results showed that HAdV-55 infection was observed only in 4% of adenovirus infected children whereas HAdV-7 infection proportioned 53%. Most cases of HAdV-55 infection were identified during March and April, whereas HAdV-7 infection occurred throughout the year. Wheezing was significantly less frequent in the HAdV-55 group. No patients infected with HAdV-55 presented with vomiting or had any underlying disease. Coinfections with other respiratory tract pathogens were frequent among children infected with either HAdV-55 or HAdV-7. CONCLUSIONS: HAdV-55 circulated in Beijing during spring and appeared to cause pediatric respiratory infections that were as severe as HAdV-7 infections. Broader surveillance studies are needed.


title: Plant-based solutions for veterinary immunotherapeutics and prophylactics

text: An alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today’s market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require “cold chain” storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current plant biotechnology developments aimed to address these challenges.


title: Taking the Longer View of COVID‐19

text: What are the prospects for dealing with COVID‐19 more effectively in the future? This editorial addresses the question from the perspective of long‐term control of coronavirus infection.


title: Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats

text: Abstract Measles virus (MV) replication in brain tissue of Lewis rats with acute (AE) and subacute (SAME) encephalitis was characterized by biochemical techniques. Messenger RNAs specific for measles virus nucleocapsid (N), phospho (P)-, matrix (M), fusion (F), and haemagglutinin (H) protein were detected in all brain extracts examined. The quantity of the individual MV mRNA species was quite different in comparison to lytically infected Vero cells. A steep gradient of MV transcripts was found in brain tissue which is most likely due to strongly attenuated transcription of mRNAs along the viral genome, representing particularly low transcription of the glycoprotein genes. In addition, in vitro translation assays only revealed synthesis of N and P protein in consistent fashion. The mRNAs for the glycoproteins did not direct the synthesis of detectable viral proteins whereas the M mRNA revealed some activity in animals with AE. The data indicate a strong restriction of the MV envelope gene expression in infected brain tissue, which is independent of the incubation time and type of the central nervous system (CNS) disease. This phenomenon which is similar to the findings observed in measles inclusion body encephalitis and subacute sclerosing panencephalitis suggest that host factors may initially be responsible for the initiation of transcriptional and translational alterations.


title: A role for galectin-3 in CD13-mediated homotypic aggregation of monocytes

text: Abstract We recently reported that anti-CD13 mAbs induce homotypic aggregation of monocytic cells. This phenomenon is signal transduction dependent and does not require CD13 aminopeptidase activity. Since CD13 is heavily glycosylated and a member of the galectin family (galectin-4) has been shown to associate with CD13 in the intestinal epithelium, we hypothesized that CD13-mediated aggregation might proceed through a carbohydrate-dependent mechanism involving galectin-3, the most highly expressed galectin on monocytes. We report here that lactose and anti-galectin-3 antibodies completely abrogate homotypic aggregation induced by anti-CD13 antibodies. Furthermore, galectin-3 co-immunoprecipitates with CD13 from resting U-937 cells and this association decreases during the aggregation process, a phenomenon that may have functional implications. Together, the results presented here point to a key role for galectin-3 in CD13-mediated homotypic aggregation of monocytic cells.


title: Mating strategy is determinant of Adenovirus prevalence in European bats

text: Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for Adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting Adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of Adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of Adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of Adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of Adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by Adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of Adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances (P. pygmaeus). These results increase our knowledge about the transmission mechanisms of Adenoviruses. Author Summary Adenoviruses are DNA viruses with a wide range of vertebrate hosts, including humans, causing ocular, respiratory and gastrointestinal diseases. Here, we focus on the prevalence of Adenoviruses in bats, which are known to be natural reservoir of many viruses, using the results of recent screenings for prevalence of these viruses in 33 European bat species. Our aim is to find association between Adenoviruses prevalence and biological and behavioral host traits, considering the heterogeneity both between and within species in order to have a deeper understanding of mechanisms of viral transmission. Our results highlight the importance of mating strategy: bats species using swarming as mating strategy are less likely to be infected by Adenoviruses. Moreover, we found that locality of capture can explain a higher prevalence of Adenovirus within species. However, no general pattern has been found in the analysis at individual level, suggesting a strong species specificity and complex viral transmission dynamics.


Tuberculosis and COVID-19 in India: Challenges and opportunities


title: SARS Coronavirus Spike Protein-Induced Innate Immune Response occurs via Activation of the NF-κB pathway in Human Monocyte Macrophages in vitro

text: A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6, IL-8) responses. We confirmed cytokine mRNA increases by real time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6nM of S produced a significant increase in IL-8 (p=0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6 nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-κB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-κB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-κB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes thru recognition by toll-like receptor (TLR)2 ligand.


title: Real-time estimation of the reproduction number of the novel coronavirus disease (COVID-19) in China in 2020 based on incidence data

text: Background: Since the first appearance in Wuhan, China in December 2019, the novel coronavirus disease (COVID-19) has posed serious threats to the public health in many Chinese places and overseas It is essential to quantify the transmissibility on real-time basis for designing public health responses Methods: We estimated the time-varying reproduction numbers in China, Hubei province and Wuhan city by using the renewable equation determined by the serial interval (SI) of COVID-19 We compare the average reproduction numbers in different periods of time to explore the effectiveness of the public health control measures against the COVID-19 epidemic Results: We estimated the reproduction numbers at 2 61 (95% CI: 2 47-2 75), 2 76 (95% CI: 2 54-2 95) and 2 71 (95% CI: 2 43-3 01) for China, Hubei province and Wuhan respectively We found that the reproduction number largely dropped after the city lockdown As of February 16, the three reproduction numbers further reduced to 0 98, 1 14 and 1 41 respectively Conclusions: The control of COVID-19 epidemic was effective in substantially reducing the disease transmissibility in terms of the reproduction number in China reduced to 0 98 as of February 16 At the same time, the reproduction number in Wuhan was probably still larger than 1, and thus the enhancement in the public health control was recommended to maintain


Letter to the Editor ”The Battle of Humans and COVID-19: A War without Smoke”


title: SARS-CoV-2 pandemic lockdown: Effects on air quality in the industrialized Gujarat state of India

text: Abstract Two weeks after the world health organization described the novel coronavirus (SARS-CoV-2) outbreak as pandemic, the Indian government implemented lockdown of industrial activities and traffic flows across the entire nation between March 24 and May 31, 2020. In this paper, we estimated the improvements achieved in air quality during the lockdown period (March 24, 2020 and April 20, 2020) compared to the pre-lockdown (January 1, 2020 and March 23, 2020) by analyzing PM2.5, PM10, SO4, CO, NO2 and O3 data from nine different air quality monitoring stations distributed across four different zones of the industrialized Gujarat state of western Indian. The Central Pollution Control Board (CPCB)-Air Quality Index (AQI) illustrated better air qualities during the lockdown with higher improvements in the zones 2 (Ahmedabad and Gandhinagar) and 3 (Jamnagar and Rajkot), and moderate improvements in the zones 1 (Surat, Ankleshwar and Vadodra) and 4 (Bhuj and Palanpur). The concentrations of PM2.5, PM10, and NO2 were reduced by 38–78%, 32–80% and 30–84%, respectively. Functioning of the power plants possibly led to less reduction in CO (3–55%) and the declined emission of NO helped to improve O3 (16–48%) contents. We observed an overall improvement of 58% in AQI for the first four months of 2020 compared to the same interval of previous year. This positive outcome resulted from the lockdown restrictions might help to modify the existing environmental policies of the region.


title: Managing People with Diabetes Fasting for Ramadan During the COVID‐19 Pandemic: A South Asian Health Foundation Update

text: The month of Ramadan forms one of the five pillars of the Muslim faith. Adult Muslims are obligated to keep daily fasts from dawn to sunset, with exceptions. This year Ramadan is due to begin on 23 April 2020 and the longest fast in the UK will be approximately 18 hours in length. In addition, due to the often high‐calorie meals eaten to break the fast, Ramadan should be seen as a cycle of fasting and feasting. Ramadan fasting can impact those with diabetes, increasing the risk of hypoglycaemia, hyperglycaemia and dehydration. This year, Ramadan will occur during the global COVID‐19 pandemic. Reports show that diabetes appears to be a risk factor for more severe disease with COVID‐19. In addition, the UK experience has shown diabetes and COVID‐19 is associated with dehydration, starvation ketosis, diabetic ketoacidosis and hyperglycaemic hyperosmolar state. This makes fasting in Ramadan particularly challenging for those Muslims with diabetes. Here, we discuss the implications of fasting in Ramadan during the COVID‐19 pandemic and make recommendations for those with diabetes who wish to fast.


title: Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same β-coronavirus group, induces sever acute respiratory disease, threatening human health. Since the outbreak of SARS-CoV-2 infection began, the disease has rapidly spread worldwide. Thus, a search for effective drugs, able to inhibit the coronavirus, has become a global pursuit. The 3C-like protease (3CL(pro)), which hydrolyzes the polyprotein to produce functional proteins, is essential for coronavirus replication and considered an important therapeutic target for diseases caused by coronaviruses, including coronavirus disease 2019 (COVID-19). Many 3CL(pro) inhibitors have been proposed, and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe the recent developments in the structure of 3CL(pro) and its function in coronavirus replication and summarize new insights into 3CL(pro) inhibitors and their mechanisms of action. We also discuss the clinical application prospects and limitations of 3CL(pro) inhibitors for COVID-19 treatment.


title: Implementation of an algorithm for selection of antimicrobial therapy for diarrhoeic calves: Impact on antimicrobial treatment rates, health and faecal microbiota

text: Abstract This study evaluated the impact of an algorithm targeting antimicrobial therapy of diarrhoeic calves on the incidence of diarrhoea, antimicrobial treatment rates, overall mortality, mortality of diarrhoeic calves and changes in the faecal microbiota. The algorithm was designed to target antimicrobial therapy in systemically ill calves from on two dairy farms. Retrospective (farm 1: 529 calves; farm 2: 639 calves) and prospective (farm 1: 639 calves; farm 2: 842 calves) cohorts were examined for 12 months before and after implementation of the algorithm. The Mantel–Haenszel test and Kaplan–Meier survival curves were used to assess the cumulative incidence risk (CIR) and time to development of each outcome before and after implementation of the algorithm. The CIR of antimicrobial treatment rates was 80% lower after implementation of the algorithm on both farms (CIR 0.19, 95% confidence interval 0.17–0.21). There was no difference in the CIR of overall mortality, but the CRI for mortality of diarrhoeic calves was lower in the period after implementation of the algorithm on one farm. The faecal microbiota of 15 healthy calves from both farms at each time period were characterised using a sequencing platform targeting the V4 region of the 16S rRNA gene. On both farms, there were significant differences in community membership and structure (parsimony P< 0.001). Use of the algorithm for treatment of diarrhoeic calves reduced antimicrobial treatment rates without a negative impact on the health of calves. However, the experimental design did not take into account the potential confounding effects of dietary changes between the study periods.


title: The immune gene repertoire of an important viral reservoir, the Australian black flying fox

text: BACKGROUND: Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity. RESULTS: Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts. CONCLUSIONS: This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection.


title: Mice Susceptible to SARS Coronavirus

text: Murine models of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) will greatly advance research on this emerging virus. When BALB/c mice were simultaneously inoculated intranasally and orally, replication of SARS-CoV was found in both lung and intestinal tissue.


Opinion piece: Microneurosurgery in COVID-19 positive patients


title: Prolonged Detection of Japanese Encephalitis Virus in Urine and Whole Blood in a Returned Short-term Traveler

text: We describe a fatal case of Japanese encephalitis virus infection following short-term travel to Thailand. Viral RNA was detected in urine and whole blood out to 26 and 28 days, respectively, after the onset of symptoms. Live virus was isolated from a urine specimen from day 14.


title: Comparative protective immunity provided by live vaccines of Newcastle disease virus or avian metapneumovirus when co-administered alongside classical and variant strains of infectious bronchitis virus in day-old broiler chicks

text: Abstract This study reports on the simultaneous administration of live NDV or aMPV subtype B vaccines alongside two live IBV (Massachusetts-H120 and 793B-CR88) vaccines in day-old maternal-antibody positive commercial broiler chicks. In the first experiment, chicks were divided into four groups; one unvaccinated and three groups vaccinated with live NDV VG/GA-Avinew, live H120 + CR88, or VG/GA-Avinew + H120 + CR88. In the second experiment, live aMPV subtype B vaccine was used in place of NDV. Clinical signs were monitored daily and oropharyngeal swabs were taken at regular intervals for vaccine virus detection. Blood was collected at 21 dpv for serology. 10 chicks from each group were challenged with virulent strains of M41 or QX or aMPV subtype B. For IBV, after 5 days post challenge (dpc), tracheal ciliary protection was assessed. For aMPV, clinical scores were recorded up to 10 dpc. For NDV, haemagglutination inhibition (HI) antibody titres were assayed as an indicator of protective immunity. In both experiments, ciliary protection for IBV vaccinated groups was maintained above 90%. The protection against virulent aMPV challenge was not compromised when aMPV, H120 and CR88 were co-administered. NDV HI mean titres in single and combined NDV-vaccinated groups remained above the protective titre (>3 log2). Both experiments demonstrated that simultaneous administration of live NDV VG/GA-Avinew or aMPV subtype B alongside H120 and CR88 vaccines does not interfere with protection conferred against NDV, IBV or aMPV.


title: Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study

text: BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world’s health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter’s search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms (“corona,” “2019-nCov,” and “COVID-19”), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news.


title: Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo

text: BACKGROUND: There is a continued need for strategies to prevent influenza. While cetylpyridinium chloride (CPC), a broad-spectrum antimicrobial agent, has an extensive antimicrobial spectrum, its ability to affect respiratory viruses has not been studied in detail. OBJECTIVES: Here, we evaluate the ability of CPC to disrupt influenza viruses in vitro and in vivo. METHODS: The virucidal activity of CPC was evaluated against susceptible and oseltamivir- resistant strains of influenza viruses. The effective virucidal concentration (EC) of CPC was determined using a hemagglutination assay and tissue culture infective dose assay. The effect of CPC on viral envelope morphology and ultrastructure was evaluated using transmission electron microscopy (TEM). The ability of influenza virus to develop resistance was evaluated after multiple passaging in sub-inhibitory concentrations of CPC. Finally, the efficacy of CPC in formulation to prevent and treat influenza infection was evaluated using the PR8 murine influenza model. RESULTS: The virucidal effect of CPC occurred within 10 minutes, with mean EC(50) and EC(2log) ranging between 5 to 20 μg/mL, for most strains of influenza tested regardless of type and resistance to oseltamivir. Examinations using TEM showed that CPC disrupted the integrity of the viral envelope and its morphology. Influenza viruses demonstrated no resistance to CPC despite prolonged exposure. Treated mice exhibited significantly increased survival and maintained body weight compared to untreated mice. CONCLUSIONS: The antimicrobial agent CPC possesses virucidal activity against susceptible and resistant strains of influenza virus by targeting and disrupting the viral envelope. Substantial virucidal activity is seen even at very low concentrations of CPC without development of resistance. Moreover, CPC in formulation reduces influenza-associated mortality and morbidity in vivo.


title: Pancreatic injury in the course of coronavirus disease 2019 (COVID‐19): a not‐so‐rare occurrence

text: Despite respiratory symptoms are typically found during the course of coronavirus disease 2019 (COVID‐19), gastrointestinal manifestations are increasingly described. However, data regarding COVID‐19‐associated pancreatic injury are still limited, as well as the mechanisms underlying COVID‐19 induced‐pancreatic damage have not been completely clarified. Herein, we described pancreatic abnormalities in six (8.5%) out of 70 patients with COVID‐19 hospitalized in our unit from February 25, 2020 to May 10, 2020. We hypothesized that pancreatic damage may be associated with several factors including direct effect of SARS‐CoV‐2, inflammatory cascade, dehydration and multiple organ dysfunction. This article is protected by copyright. All rights reserved.


title: A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas

text: B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and their approximate affinities for the antigen using only 50 μl of hybridoma cell culture supernatant. Moreover, we found that mouse hybridomas secreting IgG antibodies also have membrane form IgG expression without Igα. Based on this surface IgG, we used flow cytometry to isolate rare γ2a isotype switched variants from a γ2b antibody secreting hybridoma cell line. Also, we used fluorescent antigen to single cell sort antigen binding hybridoma cells from bulk mixture of fused hybridoma cells instead of the traditional multi-microwell plate screening and limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal antibodies specific for the native antigen identified with these methods are suitable for in vivo therapeutic uses, but also for sandwich ELISA assays, histology, flow cytometry, immune precipitation and x-ray crystallography.


title: A novel method for making human monoclonal antibodies

text: Abstract We have developed a B cell immortalization method for low B cell numbers per well using simultaneous B cell stimulation by CpG2006 and B cell infection by Epstein-Barr virus (EBV), followed by an additional CpG2006 and interleukin-2 (IL-2) stimulus. Using this method, immunoglobulin G (IgG)-producing immortalized B cell lines were generated from peripheral blood IgG+CD22+ B cells with an efficiency of up to 83%. Antibody can already be obtained from the culture supernatant after 3–4 weeks. Moreover, clonality analysis demonstrated monoclonality in 87% of the resulting immortalized B cell lines. Given the high immortalization efficiency and monoclonality rate, evidence is provided that no further subcloning is necessary. An important application of this B cell immortalization method is the characterization of (autoreactive) antibodies from patients with autoimmune disease. This could eventually lead to the identification of new autoantigens, disease markers or targets for therapy.


title: Single Center Trends in Acute Coronary Syndrome Volume and Outcomes During the COVID-19 Pandemic

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected healthcare delivery across the world. In this report, we aim to further characterize the changes in cardiac catheterization at our institution, specifically in the setting of acute coronary syndrome (ACS). METHODS: We performed a retrospective analysis of patients undergoing cardiac catheterization between December 23, 2019 and April 12, 2020 at our institution. All patients with cardiac catheterizations for ACS, ST-elevation myocardial infarction (STEMI) activation, and out-of-hospital cardiac arrest (OHCA) were analyzed. Cardiac catheterization volume, as well as clinical and procedural characteristics of patients undergoing cardiac catheterization, was compared before and during the COVID-19 pandemic. RESULTS: Patients presenting with ACS and OHCA were similar in terms of demographics and comorbidities during both time periods. The mean monthly volume for ACS cases dropped by 26% during the pandemic, which was consistent among both unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) and STEMI cases. OHCA volume decreased significantly as well (five cases per month before to zero cases during the pandemic, P = 0.01). Among patients with STEMI, initial markers of cardiac injury, door-to-balloon time, and all-cause mortality were similar in both time periods. CONCLUSIONS: With the start of the COVID-19 pandemic, there was a reduction in cardiac catheterization volume across the spectrum of ACS at our institution, which was consistent with reports from other centers across the globe. Patients with STEMI during the initial phase of the COVID-19 pandemic did not seem to have delays in presentation or significant differences in all-cause mortality at our institution.


Coronavirus lockdown: forced inactivity for the oldest old?


title: Genomic and single nucleotide polymorphism analysis of infectious bronchitis coronavirus

text: Abstract Infectious bronchitis virus (IBV) is a Gammacoronavirus that causes a highly contagious respiratory disease in chickens. A QX-like strain was analysed by high-throughput Illumina sequencing and genetic variation across the entire viral genome was explored at the sub-consensus level by single nucleotide polymorphism (SNP) analysis. Thirteen open reading frames (ORFs) in the order 5′-UTR-1a-1ab-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR were predicted. The relative frequencies of missense: silent SNPs were calculated to obtain a comparative measure of variability in specific genes. The most variable ORFs in descending order were E, 3b, 5′UTR, N, 1a, S, 1ab, M, 4c, 5a, 6b. The E and 3b protein products play key roles in coronavirus virulence, and RNA folding demonstrated that the mutations in the 5′UTR did not alter the predicted secondary structure. The frequency of SNPs in the Spike (S) protein ORF of 0.67% was below the genomic average of 0.76%. Only three SNPS were identified in the S1 subunit, none of which were located in hypervariable region (HVR) 1 or HVR2. The S2 subunit was considerably more variable containing 87% of the polymorphisms detected across the entire S protein. The S2 subunit also contained a previously unreported multi-A insertion site and a stretch of four consecutive mutated amino acids, which mapped to the stalk region of the spike protein. Template-based protein structure modelling produced the first theoretical model of the IBV spike monomer. Given the lack of diversity observed at the sub-consensus level, the tenet that the HVRs in the S1 subunit are very tolerant of amino acid changes produced by genetic drift is questioned.


title: Distinctive Cellular Response to Aluminum Based Adjuvants

text: Abstract Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant’s effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant. To test this hypothesis, human macrophages derived from peripheral monocytic cell line (THP-1) and cells derived from the human brain (primary astrocytes) were evaluated. Three commercially available formulations of ABAs (Alhydrogel, Imject alum, and Adju-Phos) were examined. Alum was also used as a reference. Cell viability, reactive oxygen species formation, and production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were quantified. Cells were exposed to different concentrations (10-100 µg/mL) of the adjuvants for 24 h or 72 h. The two FDA approved adjuvants (Alhydrogel and Adju-Phos) decreased cell viability in both cell types. At the 72 h time point, the decrease in viability was accompanied with increased ROS formation. The size of the aluminum agglomerates was not relatable to the changes observed. After exposure to ABAs, astrocytes and macrophages presented a distinct profile of cytokine secretion which may relate to the function and unique characteristics of each cell type. These variations indicate that aluminum adjuvants may have differing capability of activating cells of different origin and thus their utility in specific vaccine design should be carefully assessed for optimum efficacy.


title: Pharmacologic modulation of ACE2 expression

text: Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.


title: Efficient Autoproteolytic Processing of the MHV-A59 3C-like Proteinase from the Flanking Hydrophobic Domains Requires Membranes

text: Abstract The replicase gene of the coronavirus MHV-A59 encodes a serine-like proteinase similar to the 3C proteinases of picornaviruses. This proteinase domain is flanked on both sides by hydrophobic, potentially membrane-spanning, regions. Cell-free expression of a plasmid encoding only the 3C-like proteinase (3CLpro) resulted in the synthesis of a 29-kDa protein that was specifically recognized by an antibody directed against the carboxy-terminal region of the proteinase. A protein of identical mobility was detected in MHV-A59-infected cell lysates.In vitroexpression of a plasmid encoding the 3CLpro and portions of the two flanking hydrophobic regions resulted in inefficient processing of the 29-kDa protein. However, the efficiency of this processing event was enhanced by the addition of canine pancreatic microsomes to the translation reaction, or removal of one of the flanking hydrophobic domains. Proteolysis was inhibited in the presence ofN-ethylmaleimide (NEM) or by mutagenesis of the catalytic cysteine residue of the proteinase, indicating that the 3CLpro is responsible for its autoproteolytic cleavage from the flanking domains. Microsomal membranes were unable to enhance thetransprocessing of a precursor containing the inactive proteinase domain and both hydrophobic regions by a recombinant 3CLpro expressed fromEscherichia coli.Membrane association assays demonstrated that the 29-kDa 3CLpro was present in the soluble fraction of the reticulocyte lysates, while polypeptides containing the hydrophobic domains associated with the membrane pellets. With the help of a viral epitope tag, we identified a 22-kDa membrane-associated polypeptide as the proteolytic product containing the amino-terminal hydrophobic domain.


title: Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

text: Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated.


title: Erythema multiforme‐like lesions in children and COVID‐19

text: During examination of cases of chilblains in children and adolescents, we identified four patients who also showed skin lesions similar to erythema multiforme (EM). They had no other known triggers for EM. One of them had a positive PCR for SARS‐CoV‐2, while the other 3 were negative. Skin biopsies from two patients showed features not typical of EM, such as deep perivascular and perieccrine infiltrate and absence of necrosis of keratinocytes. Immunohistochemistry for SARS‐CoV/SARS‐CoV‐2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies. All patients had an excellent outcome, and had minimal or no systemic symptoms. The coincidence of EM, a condition commonly related to viruses, and chilblains in the setting of COVID‐19, as well as the positivity for SARS‐CoV/SARS‐CoV‐2 spike protein by immunohistochemistry strongly suggest a link between EM‐like lesions and SARS‐CoV‐2.


title: A medium-throughput screen for inhibitors of human metapneumovirus

text: Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.


title: Effects of intravenously infused Fluosol-DA 20% in rats

text: Abstract Rats were injected with a fractionated 50 ml/kg dose of Fluosol®-DA 20% with and without exposure to 100% oxygen. Animals were killed at 24, 43, 92, and 183 days post-treatment and samples taken for hematological, hepatic enzyme, histological, and perfluorochemical analyses. There were no significant differences in hemograms or hepatic enzyme findings between treatment and control groups. Differences in organ weights and histology were a result of perfluorochemical (PFC) accumulation in the tissues of treated animals. All changes were reversible. There were no effects from breathing high oxygen levels in either treatment or control animals.


Depression, Dependence and Prices of the COVID-19-Crisis


title: Siniperca chuatsi rhabdovirus (SCRV) induces autophagy via PI3K/Akt-mTOR pathway in CPB cells

text: Autophagy is an important mechanism for organisms to eliminate viruses and other intracellular pathogens. Siniperca chuatsi rhabdovirus (SCRV) is an agent that has caused devastating losses in Chinese perch (Siniperca chuatsi) industry. But the role of autophagy in Siniperca chuatsi rhabdovirus (SCRV) infection is not clearly understood. In this study, we identified that SCRV infection triggered autophagy in CPB cells, which was demonstrated by the appearance of the membrane vesicles, GFP-LC3 punctuate pattern, conversion of LC3-I to LC3-II, and the co-localization of autophagosomes and lysosomes. The changes of autophagy flux in SCRV infection indicated that autophagy was inhibited at the early stage of SCRV infection, but was promoted at the late stage. UV-inactivated SCRV can induce autophagy, suggesting that SCRV replication is not essential for the induction of autophagy. Furthermore, we found inducing autophagy with Rapa inhibited SCRV proliferation, but inhibiting autophagy with 3-MA or CQ increased SCRV production in CPB cells. Then we assessed the effects of PI3K/Akt-mTOR signaling pathway on SCRV induced autophagy. We found that SCRV infection activated PI3K/AKT signaling pathway at 4 hpi, but inhibited it at 8 hpi. SCRV-N mRNA and protein level were decreased by inhibiting PI3K with LY294002, but increased by activating PI3K with 740Y–P. Those results indicated that SCRV infection induced autophagy via the PI3K/Akt-mTOR signal pathway, which will provide new insights into SCRV pathogenesis and antiviral treatment strategies.


title: Prevalence of depression and its impact on quality of life among frontline nurses in emergency departments during the COVID-19 outbreak

text: BACKGROUND: Frontline medical staff exposed to the novel coronavirus disease (COVID-19) could be psychologically and mentally exhausted. This study examined the prevalence of depressive symptoms (depression hereafter) and its correlates and the association between depression and quality of life (QOL) in Emergency Department (ED) nurses during the COVID-19 pandemic in China. METHODS: This national, cross-sectional online survey was conducted between March 15 to March 20, 2020 in China. Depression and QOL were measured using the 9-item Patient Health Questionnaire, and the World Health Organization Quality of Life Questionnaire-Brief Version, respectively. RESULTS: The overall prevalence of depression in 1,103 ED nurses was 43.61% (95% CI=40.68%-46.54%). Multiple logistic regression analysis revealed that working in tertiary hospitals (OR=1.647, P=0.009), direct patient care of COVID-19 patients (OR=1.421, P=0.018), and currently smoking (OR=3.843, P<0.001) were significantly associated with depression. After controlling for covariates, nurses with depression had an overall lower quality of life compared to those without (F((1,1103))=423.83, P<0.001). CONCLUSION: Depression is common among ED nurses during the COVID-19 pandemic. Considering the negative impact of depression on quality of patient care and nurses’ quality of life, a heightened awareness and early treatment of depression for frontline ED nurses should be provided.


Pathogens and autophagy: subverting to survive


title: SARS-CoV-2 Infection and High-Risk Non-Muscle-Invasive Bladder Cancer: Are There Any Common Features?

text: BACKGROUND: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death. SUMMARY: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. KEY MESSAGES: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field.


title: Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project

text: The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination.


title: Prediction of bifurcations by varying critical parameters of COVID-19

text: Coronavirus disease 2019 is a recent strong challenge for the world. In this paper, an epidemiology model is investigated as a model for the development of COVID-19. The propagation of COVID-19 through various sub-groups of society is studied. Some critical parameters, such as the background of mortality without considering the disease state and the speed of moving people from infected to resistance, affect the conditions of society. In this paper, early warning indicators are used to predict the bifurcation points in the system. In the interaction of various sub-groups of society, each sub-group can have various parameters. Six cases of the sub-groups interactions are studied. By coupling these sub-groups, various dynamics of the whole society are investigated.


Angiotensin II for the Treatment of COVID-19–Related Vasodilatory Shock


title: Does the novel coronavirus 2019 like heart more than the other family members of coronaviruses?

text: The disaster due to the novel coronavirus disease 2019 (COVID-19) around the world has made investigators enthusiastic about working on different aspects of COVID-19. However, although the pandemic of COVID-19 has not yet ended, it seems that COVID-19 compared to the other coronavirus infections (the Middle East Respiratory Syndrome [MERS] and Severe Acute Respiratory Syndrome [SARS]) is more likely to target the heart. Comparing the previous presentations of the coronavirus family and the recent cardiovascular manifestations of COVID-19 can also help in predicting possible future challenges and taking measures to tackle these issues.


title: Recognition of Lys48-linked di-ubiquitin and deubiquitinating activities of the SARS coronavirus papain-like protease

text: Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific poly-ubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The Severe Acute Respiratory Syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1–S1′ preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.


title: In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors

text: Abstract Coronaviruses with the largest viral genomes are positive-sense RNA viruses associated with a history of global epidemics such as the severe respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and recently the coronavirus disease 2019 (COVID-19). There has been no vaccines or drugs available for the treatment of human coronavirus infections to date. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. We have used molecular docking approach and have successfully identified the best lead molecules for each enzyme target. Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. Hence both these lead molecules can be further taken for wet-lab experimentation studies before repurposing them as anti-coronaviral drug candidates.


title: Fatal outbreaks in dogs associated with pantropic canine coronavirus in France and Belgium

text: Infection with pantropic canine coronavirus was detected during outbreaks in France and Belgium. This was concurrent in most cases with canine parvovirus 2c. One outbreak was a deadly acute systemic disease with a single pantropic canine coronavirus infection. This is the first report of a fatality associated with pantropic canine coronavirus alone outside Italy.


title: Acute Respiratory Distress Syndrome

text: The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma, and is present in ~10% of all intensive care unit patients worldwide. Despite some improvements over the past decades, mortality remains high at 30–40% in most studies. Pathologic specimens from patients with ARDS most frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory edema fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with recent proposed modifications for under-resourced settings and for pediatric patients. Patient management focuses on implementing a lung-protective ventilation strategy; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to suffer ongoing functional and/or psychologic sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, prognostic and/or predictive enrichment in clinical studies to identify responsive subsets, and ongoing efforts to understand fundamental mechanisms of lung injury that may respond to specific treatments.


title: Impact of urbanization on pollution-related agricultural input intensity in Hubei, China

text: Agricultural input intensity increases significantly during the rapid urbanization in China, which has contributed to the increasingly serious non-point pollution. Using the vector autoregression (VAR) model, this study analyzes the impact of urbanization on pollution-related agricultural input intensity in Hubei, China. Results of an impulse response function analysis reveal that pesticide use intensity continues to rise following shocks from the urban population proportion and the secondary and tertiary industry proportion. Responses of chemical fertilizer intensity first decrease and then increase subjected to the shocks from the urban population proportion and secondary and tertiary industry proportion. The intensity of agricultural plastic film use first increases and then decreases when receives the shocks from the urban population proportion which is the opposite to the response to the shock from the secondary and tertiary industry proportion. In addition, the responses of pesticide use intensity, chemical fertilizer use intensity and agricultural plastic film use intensity trend decrease following their own shocks after positive initial responses. The variance decomposition results demonstrate that the shocks due to pesticide use intensity, chemical fertilizer use intensity and agricultural plastic film use intensity generally explain the largest proportion of their own variation over the 10-year horizon. However, an increase in the urban population proportion plays a critical role in determining the variations of pesticide use intensity in late periods, it account for 56.88% the variations in the tenth period. And the contribution of the urban population proportion to the variations in agricultural plastic film use intensity increases consistently, it account for 33.74% of the variations in the tenth period. Therefore, the hidden drivers of these phenomena need to be further understood regarding the relationships between urbanization and diffuse pollution from agricultural production.


title: Serological Study of An Imported Case of Middle East Respiratory Syndrome and His Close Contacts in China, 2015

text: The first imported Middle East respiratory syndrome (MERS) case in China was identified in May 2015. We determined the kinetics of antibody (IgG and IgM) and neutralizing antibodies against MERS-coronavirus (MERS-CoV) in this case before discharge. Moreover, no seroconversion was found among 53 close contacts by anti-MERS IgG antibody enzyme-linked immunosorbent assay (ELISA) of paired serum samples. These findings suggest that neither community nor nosocomial transmission of MERS-CoV occurred in China.


title: COVID-19 and Moral Imperialism in Multinational Clinical Research

text: Abstract A TV debate in April 2020 between two French doctors regarding the benefits of testing a coronavirus vaccine in Africa where there are no masks or treatments available has led to international criticism. This case highlights a problematic ethical double standard in multinational clinical research: trials that would be considered unethical in high income countries (e.g., placebo-controlled where there is an existing treatment) are nonetheless justified in low-and-middle-income countries because the existing standards of care are less (i.e., no access to a treatment). Underlying this ethical double standard in some multinational clinical trials is a moral imperialism and persistent colonialist thinking that must be rejected.


title: Noise and Room Acoustic Conditions in a Tertiary Referral Hospital, Seoul National University Hospital

text: BACKGROUND AND OBJECTIVES: Noise levels and room acoustic parameters at a tertiary referral hospital, Seoul National University Hospital (SNUH) in Korea, are investigated. MATERIALS AND METHODS: Through a questionnaire, acoustically problematic rooms are identified. Noise levels in emergency rooms (ERs) and intensive care units (ICUs) are measured over about three days. Acoustically critical and problematic rooms in the otolaryngology department are measured including examination rooms, operating rooms, nurse stations, receptions, and patient rooms. RESULTS: The A-weighted equivalent noise level, L(Aeq), ranges from 54 to 56 dBA, which is at least 10 dB lower than the noise levels of 65 to 73 dBA measured in American ERs. In an ICU, the noise level for the first night was 66 dBA, which came down to 56 dBA for the next day. The noise levels during three different ear surgeries vary from 57 to 62 dBA, depending on the use of surgical drills and suctions. The noise levels in a patient room is found to be 47 dBA, while the nurse stations and the receptions have high noise levels up to 64 dBA. The reverberation times in an operation room, examination room, and single patient room are found to be below 0.6 s. CONCLUSIONS: At SNUH, the nurse stations and receptions were found to be quite noisy. The ERs were quieter than in the previous studies. The measured reverberation times seemed low enough but some other nurse stations and examination rooms were not satisfactory according to the questionnaire.


title: A rapid one‐step immunochromatographic test strip for rabies detection using canine serum samples

text: We developed an immunochromatographic test strip using colloidal gold‐coated staphylococcal protein A (SPA) for the detection of rabies antibody in canine serum samples. The recombinantly expressed rabies virus phosphoprotein (RV‐P) and the anti‐staphylococcal protein A (anti‐SPA) polyclonal antibody were coated on the test (T) and control (C) lines on a nitrocellulose membrane, respectively. This layout is designed such that the polyclonal antibody in canine serum is captured by the colloidal gold–SPA conjugates, before the rabies antibody complex is specifically selected by the RV‐P deposited on the T line, forming a ‘sandwich’ pattern. Unbound excess colloidal SPA then proceeds to the control line where SPA specifically interacts with the anti‐SPA antibody, producing a red precipitation at the C line, indicating the validity of the strip. We tested 165 canine serum samples with the strips, and the results were compared with those obtained using ELISA. The specificity and sensitivity of ICTS were found to be 93·1 and 92·2%, respectively. As a rapid technique, not demanding expensive instrumentation, the strip offers potential in disease monitoring, especially in rabies‐endemic developing countries. SIGNIFICANCE AND IMPACT OF THE STUDY: Simple and cheap techniques to detect rabies virus or monitor immunity against it are central in maintaining epidemiological control over the disease, particularly in endemic developing countries. While many techniques meet this requirement, they are confined to this usage as they are time‐consuming and demand expensive instrumentation. Our immunochromatographic test strip can detect rabies antibody with high specificity and sensitivity; the output can be measured with naked eye. It allows safe and quick detection that will be of value in the surveillance of the immunization status of potential targets in rabies‐endemic regions and will aid disease control.


title: Importance of the evaluation of systemic microvascular flow and reactivity in critically ill patients with coronavirus disease 2019 — COVID-19()

text: Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.


title: The cGAS-STING Defense Pathway and Its Counteraction by Viruses

text: Upon viral infection, host cells mount a concerted innate immune response involving type I interferon and pro-inflammatory cytokines to enable elimination of the pathogen. Recently cGAS and STING have been identified as intracellular sensors that activate the interferon pathway in response to virus infection and thus mediate host defense against a range of DNA and RNA viruses. Here we review how viruses are sensed by the cGAS-STING signaling pathway as well as how viruses modulate this pathway. Mechanisms utilized by viral proteins to inhibit cGAS and/or STING are also discussed. On the flip side, host cells have also evolved strategies to thwart viral immune escape. The balance between host immune control and viral immune evasion is pivotal to viral pathogenesis and we discuss this virus-host stand-off in the context of the cGAS-STING innate immune pathway.


title: Chapter 546 Coronavirus Picornain-like Cysteine Proteinase

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 544 is Coronavirus Picornain-like Proteinase. Keywords nsp5 proteinase, 3C-like proteinase, 3CLpro, cysteine proteinase, coronavirus, Mpro, picornain-like.


title: Research Investments in Global Health: A Systematic Analysis of UK Infectious Disease Research Funding and Global Health Metrics, 1997–2013

text: BACKGROUND: Infectious diseases account for a significant global burden of disease and substantial investment in research and development. This paper presents a systematic assessment of research investments awarded to UK institutions and global health metrics assessing disease burden. METHODS: We systematically sourced research funding data awarded from public and philanthropic organisations between 1997 and 2013. We screened awards for relevance to infection and categorised data by type of science, disease area and specific pathogen. Investments were compared with mortality, disability-adjusted life years (DALYs) and years lived with disability (YLD) across three time points. FINDINGS: Between 1997–2013, there were 7398 awards with a total investment of £3.7 billion. An increase in research funding across 2011–2013 was observed for most disease areas, with notable exceptions being sexually transmitted infections and sepsis research where funding decreased. Most funding remains for pre-clinical research (£2.2 billion, 59.4%). Relative to global mortality, DALYs and YLDs, acute hepatitis C, leishmaniasis and African trypanosomiasis received comparatively high levels of funding. Pneumonia, shigellosis, pertussis, cholera and syphilis were poorly funded across all health metrics. Tuberculosis (TB) consistently attracts relatively less funding than HIV and malaria. INTERPRETATION: Most infections have received increases in research investment, alongside decreases in global burden of disease in 2013. The UK demonstrates research strengths in some neglected tropical diseases such as African trypanosomiasis and leishmaniasis, but syphilis, cholera, shigellosis and pneumonia remain poorly funded relative to their global burden. Acute hepatitis C appears well funded but the figures do not adequately take into account projected future chronic burdens for this condition. These findings can help to inform global policymakers on resource allocation for research investment.


title: Sterols of the marine sponge Petrosia weinbergi: implications for the absolute configurations of the antiviral orthoesterols and weinbersterols

text: Abstract The marine sponge Petrosia weinbergi was found to contain isofucosterol and clionasterol as its major sterols. The rare cyclopropyl sterol (24S,28S)-24,28-methylenestigmast-5-en-3β-ol, previously detected as only 0.07% of the total sterols of a pelagophytic alga Pulvinaria sp., made up 6.6% of the total sterols. These sterols are believed to be the biosynthetic precursors of the antiviral orthoesterols and weinbersterols found in the same sponge. Based on the side chains of the isolated sterols, the absolute configurations of the antiviral steroid side chains are assigned to be (24R,28S)- for orthoesterol B, (24R)- for orthoesterol C, and (24S,28S)- for weinbersterols A and B.


title: Value of initial chest radiographs for predicting clinical outcomes in patients with severe acute respiratory syndrome

text: Purpose To determine whether the initial chest radiograph is helpful in predicting the clinical outcome of patients with severe acute respiratory syndrome (SARS). Methods Of 343 patients who met the World Health Organization’s case definition of probable SARS and who had been admitted to a regional hospital in Hong Kong, 201 patients had laboratory evidence of SARS coronavirus infection. The initial frontal chest radiographs of these 201 patients were assessed in a blinded fashion by 3 radiologists; individual findings were accepted if at least 2 of the radiologists concurred. Independent predictors of an adverse outcome, defined as the need for assisted ventilation, death, or both, were identified by multivariate analysis. Results Bilateral disease and involvement of more than two zones on the initial chest radiograph were associated with a higher risk of liver impairment and poor clinical outcome. Forty-two patients (21%) developed an adverse outcome. Multivariate analysis showed that lung involvement of more than two zones (odds ratio [OR] = 7.0; 95% confidence interval [CI]: 2.7 to 17.9), older age (OR for each decade of life = 1.5; 95% CI: 1.1 to 2.0), and shortness of breath on admission (OR = 2.8; 95% CI: 1.1 to 7.4) were independent predictors of an adverse outcome. Conclusion Frontal chest radiographs on presentation may have prognostic value in patients with SARS.


title: Systematic review on respiratory syncytial virus epidemiology in adults and the elderly in Latin America

text: Abstract Objectives The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. Methods A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered. Results Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%). Conclusions Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.


title: Use of baculovirus expression system for generation of virus-like particles: Successes and challenges

text: Abstract The baculovirus expression system (BES) has been one of the versatile platforms for the production of recombinant proteins requiring multiple post-translational modifications, such as folding, oligomerization, phosphorylation, glycosylation, acylation, disulfide bond formation and proteolytic cleavage. Advances in recombinant DNA technology have facilitated application of the BES, and made it possible to express multiple proteins simultaneously in a single infection and to produce multimeric proteins sharing functional similarity with their natural analogs. Therefore, the BES has been used for the production of recombinant proteins and the construction of virus-like particles (VLPs), as well as for the development of subunit vaccines, including VLP-based vaccines. The VLP, which consists of one or more structural proteins but no viral genome, resembles the authentic virion but cannot replicate in cells. The high-quality recombinant protein expression and post-translational modifications obtained with the BES, along with its capacity to produce multiple proteins, imply that it is ideally suited to VLP production. In this article, we critically review the pros and cons of using the BES as a platform to produce both enveloped and non-enveloped VLPs.


title: Effect of colostrum quantity and quality on neonatal calf diarrhoea due to Cryptosporidium spp. infection

text: Abstract This study was conducted to assess the effect of colostrum quality and quantity on Cryptosporidium spp. calf diarrhoea in an intensive dairy cattle farm in Greece. Faecal samples were collected from 100 dairy calves randomly selected and born during all 4 seasons (March 2015 to May 2016) of the year. In total, 71% of the selected calves were positive for Cryptosporidium spp. oocysts. The statistical analysis revealed influence of colostrum quality on faecal score. Linear regression showed that the colostrum quantity during the first day of life was negatively associated with the number of Cryptosporidium spp. oocysts in faeces. During multivariable analysis, the variables representing the quality of colostrum and the season of the calf’s birth were identified as confounders. Cryptosporidium spp. is a common pathogen participating in neonatal calf diarrhoea. Colostrum management and season influence the number of Cryprosporidium spp. oocysts and faecal consistency. The above findings demonstrate novel risk factors that should be included in the strategic approaches to control cryptosporidiosis in newborn calves.


title: Pandemia COVID-19, la nueva emergencia sanitaria de preocupación internacional: una revisión

text: Resumen A finales de diciembre del 2019, se reportaron una serie de casos de neumonía atípica, en ese momento, de origen desconocido en Wuhan, China. Días más tarde se identificó al agente etiológico como un nuevo coronavirus. A este nuevo coronavirus, se le llamó SARS-CoV-2 y a la enfermedad que produce se le denominó COVID-19. El origen de este nuevo virus se presume zoonótico siendo los murciélagos su probable vector. Debido al acelerado número de contagios y muertes que se produjeron primero en China y posteriormente alrededor del mundo, la infección de este virus pasó rápidamente de ser un brote aislado en una región china, a convertirse en una emergencia sanitaria de preocupación internacional y posteriormente, en una pandemia. El propósito de esta revisión es estudiar la información más relevante y actual del patógeno, así como la epidemiología, patología, características clínicas, transmisión, prevención y tratamiento de la enfermedad. Abstract In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.


title: Characterization of an outbreak of astroviral diarrhea in a group of cheetahs (Acinonyx jubatus)

text: Abstract A Mamastrovirus was identified in an outbreak of diarrhea in cheetahs (Acinonyx jubatus). Five young adult and two adult cheetahs presented with lethargy, anorexia, watery diarrhea and regurgitation over an 11-day period. Fecal samples were submitted for electron microscopy and culture. Electron microscopy results revealed particles morphologically consistent with an astrovirus, and no other viral pathogens or significant bacterial pathogens were identified. The astrovirus was confirmed and sequenced using consensus astroviral PCR, resulting in a 367 base pair partial RNA-dependent-RNA polymerase (RdRp) product and a 628 base pair partial capsid product. Bayesian and maximum likelihood phylogenetic analyses were performed on both the RdRp and the capsid protein segments. All animals were monitored and treated with bismuth subsalicylate tablets (524mg PO BID for 5 days), and recovered without additional intervention. This is the first report we are aware of documenting an astrovirus outbreak in cheetah.


title: Novel concepts in virally induced asthma

text: Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness.


title: Dromedary camels in northern Mali have high seropositivity to MERS-CoV

text: A high percentage (up to 90%) of dromedary camels in the Middle East as well as eastern and central Africa have antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV). Here we report comparably high positivity of MERS-CoV antibodies in dromedary camels from northern Mali. This extends the range of MERS-CoV further west in Africa than reported to date and cautions that MERS-CoV should be considered in cases of severe respiratory disease in the region.


title: Impact of the COVID-19 pandemic on patients suffering from musculoskeletal tumours

text: BACKGROUND: The aim of the current study was to evaluate the impact of the coronavirus disease (COVID-19) pandemic on musculoskeletal tumor service by conducting an online survey of physicians. METHODS: The survey was conducted among the members of the ISOLS (International Society of Limb Salvage) and the EMSOS (European Musculo-Skeletal Oncology Society). The survey consisted of 20 questions (single, multiple-response, ranked): origin and surgical experience of the participant (four questions), potential disruption of healthcare (12 questions), and influence of the COVID-19 pandemic on the particular physician (four questions). A matrix with four different response options was created for the particular surgical procedures). RESULTS: One hundred forty-nine physicians from five continents completed the survey. Of the respondents, 20.1% and 20.7% stated that surgery for life-threatening sarcomas were stopped or delayed, respectively. Even when the malignancy was expected to involve infiltration of a neurovascular bundle or fracture of a bone, still 13.8% and 14.7% of the respondents, respectively, stated that surgery was not performed. In cases of pending fractures of bone tumors, 37.5 to 46.2% of operations were canceled. CONCLUSION: The SARS-CoV-2 pandemic caused a significant reduction in healthcare (surgery, radiotherapy, chemotherapy) for malignancies of the musculoskeletal system. Delaying or stopping these treatments is life-threatening or can cause severe morbidity, pain, and loss of function. Although the coronavirus disease causes severe medical complications, serious collateral damage including death due to delayed or untreated sarcomas should be avoided. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00264-020-04636-4) contains supplementary material, which is available to authorized users.


title: E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation

text: Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.


title: Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives

text: BACKGROUND: In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families. METHODS: 266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts. RESULTS: 96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012. CONCLUSION: Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced.


title: Ascertainment rate of novel coronavirus disease (COVID-19) in Japan

text: Abstract Objective To estimate the ascertainment rate of novel coronavirus (COVID-19). Methods We analyzed the epidemiological dataset of confirmed cases with COVID-19 in Japan as of 28 February 2020. A statistical model was constructed to describe the heterogeneity of reporting rate by age and severity. We estimated the number of severe and non-severe cases, accounting for under-ascertainment. Results The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50), indicating that unbiased number of non-cases would be more than twice the reported count. Conclusions Severe cases are twice more likely diagnosed and reported than other cases. Considering that reported cases are usually dominated by non-severe cases, the adjusted total number of cases is also about a double of observed count. Our finding is critical in interpreting the reported data, and it is advised to interpret mild case data of COVID-19 as always under-ascertained.


title: The epidemiology and clinical characteristics of co‐infection of SARS‐CoV‐2 and influenza viruses in patients during COVID‐19 outbreak

text: In this study, we performed a single‐centred study of 307 SARS‐CoV‐2 infected patients. It was found that co‐infection of SARS‐CoV‐2 and influenza virus was common during COVID‐19 outbreak. And patients co‐infected with SARS‐CoV‐2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID‐19 outbreak. This article is protected by copyright. All rights reserved.