title: High success and low mortality rates with non-invasive ventilation in influenza A H1N1 patients in a tertiary hospital

text: BACKGROUND: In 2009, an outbreak of respiratory illness caused by influenza A H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU) admission. The use of non-invasive ventilation (NIV) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers. METHODS: Describe the respiratory profile, the mortality rate, and the benefit of using NIV in patients with confirmed diagnosis of influenza AH1N1 who were admitted in the ICU during the year 2009. RESULTS: A total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real-time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was present in 70% of patients. The median Acute Physiology and Chronic Health Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF, 85.7% needed NIV and 14% needed invasive MV at admission. Our success rate (41.6%) with NIV was higher than that described by others. The hospital mortality rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already on endemic alert in other countries. The population was already aware of the symptoms and the health-care system of the treatment. This allowed patients to be properly and promptly treated for influenza A H1N1, while health-care workers took protective measures to avoid contamination. CONCLUSION: In our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza A H1N1.


Genome editing for disease resistance in pigs and chickens


docid: yboejhox

title: Common Respiratory Diseases

text: The self-medication phenomenon in upper respiratory tract infections, rhinosinusitis, asthma, and chronic obstructive pulmonary disease are significant and will continue to increase. Current level of evidence is poor because of the small number of good quality studies, small sample size, short duration, and variation in the composition of the herbal interventions or therapies. The current review points to several potential therapies that could be effective either alone, or as adjuncts to conventional therapies.


title: Insights into the development of chemical probes for RNA

text: Over the past decade, the RNA revolution has revealed thousands of non-coding RNAs that are essential for cellular regulation and are misregulated in disease. While the development of methods and tools to study these RNAs has been challenging, the power and promise of small molecule chemical probes is increasingly recognized. To harness existing knowledge, we compiled a list of 116 ligands with reported activity against RNA targets in biological systems (R-BIND). In this survey, we examine the RNA targets, design and discovery strategies, and chemical probe characterization techniques of these ligands. We discuss the applicability of current tools to identify and evaluate RNA-targeted chemical probes, suggest criteria to assess the quality of RNA chemical probes and targets, and propose areas where new tools are particularly needed. We anticipate that this knowledge will expedite the discovery of RNA-targeted ligands and the next phase of the RNA revolution.


Health status of patients with Autoimmune Liver Disease during SARS-CoV-2 outbreak in northern Italy


title: Genetic diversity and cross-species transmission of kobuviruses in Vietnam

text: Cross-species transmission of viruses poses a sustained threat to public health. Due to increased contact between humans and other animal species the possibility exists for cross-species transmissions and ensuing disease outbreaks. By using conventional PCR amplification and next generation sequencing, we obtained 130 partial or full genome kobuvirus sequences from humans in a sentinel cohort in Vietnam and various mammalian hosts including bats, rodents, pigs, cats, and civets. The evolution of kobuviruses in different hosts was analysed using Bayesian phylogenetic methods. We estimated and compared time of origin of kobuviruses in different host orders; we also examined the cross-species transmission of kobuviruses within the same host order and between different host orders. Our data provide new knowledge of rodent and bat kobuviruses, which are most closely related to human kobuviruses. The novel bat kobuviruses isolated from bat roosts in Southern Vietnam were genetically distinct from previously described bat kobuviruses, but closely related to kobuviruses found in rodents. We additionally found evidence of frequent cross-species transmissions of kobuviruses within rodents. Overall, our phylogenetic analyses reveal multiple cross-species transmissions both within and among mammalian species, which increases our understanding of kobuviruses genetic diversity and the complexity of their evolutionary history.


title: Infecciones virales de las vías respiratorias en la Unidad de Cuidados Intensivos Neonatales

text: Resumen Introducción Las infecciones virales respiratorias son causa de importante morbimortalidad en recién nacidos prematuros. Hemos realizado un estudio prospectivo en nuestra unidad de cuidados intensivos neonatales (UCIN) para determinar la incidencia de infecciones respiratorias, su impacto, epidemiología y pronóstico en neonatos de alto riesgo. Pacientes y métodos Estudio prospectivo realizado entre septiembre del 2011 y mayo del 2013 entre todos los recién nacidos < 32 semanas de edad gestacional y aquellos niños cuya patología pudiera dar lugar a pensar en un ingreso superior a las 2 semanas. Se recogieron aspirados nasofaríngeos (ANF) el primer día de vida y semanalmente hasta el alta para estudio virológico mediante reacción en cadena de polimerasa. En los casos en los que los niños presentaban síntomas respiratorios, se procedió a recoger un nuevo ANF. El pediatra cumplimentó un cuestionario con los datos clínicos. Resultados Se estudió a 60 niños; 30 (50%) de ellos con una edad gestacional < 32 semanas y 36 (60%) con un peso < 1.500 g. Se recogió un total de 256 ANF, 24 de los cuales resultaron positivos (9,3%). Estas 24 muestras positivas correspondieron solo a 13 niños (21,6% de los pacientes). De ellos, 9 resultaron sintomáticos y presentaron 11 episodios de infección (2 pacientes experimentaron 2 episodios diferentes con control negativo entre ellos). El virus más frecuentemente identificado —el 79% de las muestras (19)— fue el rinovirus (RV). El dato clínico más frecuente fue la presencia o incremento de apneas (75%) y la necesidad de oxigenoterapia. Conclusiones Las infecciones por RV son frecuentes en la UCIN y los recién nacidos pretérmino tienen un alto riesgo de presentar infecciones de relevancia clínica. Abstract Introduction Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. Patients and methods From September 2011 to May 2013 a prospective study was conducted in all preterm infants < 32 weeks gestational age and in all term newborns admitted to NICU for any pathology that are anticipated to have an income exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected in this moment. A clinical form was filled by the physician. Results A total of 60 infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%) weighing less than 1500 grams. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increased of apneas (75%) and the needed of oxygenotherapy. Conclusions HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance.


Thirty Years into the Genomics Era: Tumor Viruses Led the Way


title: Genotyping of clinically relevant human adenoviruses by array-in-well hybridization assay

text: A robust oligonucleotide array-in-well hybridization assay using novel up-converting phosphor reporter technology was applied for genotyping clinically relevant human adenovirus types. A total of 231 adenovirus-positive respiratory, ocular swab, stool and other specimens from 219 patients collected between April 2010 and April 2011 were included in the study. After a real-time PCR amplification targeting the adenovirus hexon gene, the array-in-well assay identified the presence of B03 (n = 122; 57.5% of patients), E04 (29; 13.7%), C02 (21; 9.9%), D37 (14; 6.6%), C01 (12; 5.7%), C05 (5; 2.4%), D19 (4; 1.9%), C06 (2; 0.9%), D08 (1; 0.5%), A31 (1; 0.5%) and F41 (1; 0.5%) genotypes among the clinical sample panel. The typing result was obtained for all specimens that could be amplified (n = 223; 97%), and specificity of the typing was confirmed by sequencing specimens representing each of the different genotypes. No hybridization signal was obtained in adenovirus-negative specimens or specimens with other viruses (n = 30). The array-in-well hybridization assay has great potential as a rapid and multiplex platform for the typing of clinically relevant human adenovirus genotypes in different specimen types.


title: The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent

text: Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.


docid: mqitzpkx

title: Nanotechnology in vaccine delivery

text: Abstract With very few adjuvants currently being used in marketed human vaccines, a critical need exists for novel immunopotentiators and delivery vehicles capable of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine components could facilitate the development of novel vaccines for viral and parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this review, we discuss clinical trial results for various vaccine adjuvants and delivery vehicles being developed that are approximately nanoscale (<1000 nm) in size. Humoral immune responses have been observed for most adjuvants and delivery platforms while only viral vectors, ISCOMs and Montanide™ ISA 51 and 720 have shown cytotoxic T cell responses in the clinic. MF59 and MPL® have elicited Th1 responses, and virus-like particles, non-degradable nanoparticles and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical successes reported for intranasal delivery of viral vectors and proteosomes and oral delivery of a VLP vaccine.


title: Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses

text: Abstract Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl. To analyze infection of enterocytes is a challenging task as culture systems for differentiated intestinal epithelial cells are not readily available and often have a life span that is too short for infection studies. Precision-cut intestinal slices (PCIS) from chicken embryos were prepared and shown that the epithelial cells lining the lumen of the intestine are viable for up to 4 days. Using lectin staining, it was demonstrated that α2,3-linked sialic acids, the preferred receptor determinants of avian influenza viruses, are present on the apical side of the epithelial cells. Furthermore, the epithelial cells (at the tips) of the villi were shown to be susceptible to infection by an avian influenza virus of the H9N2 subtype. This culture system will be useful to analyze virus infection of intestinal epithelial cells and it should be applicable also to the intestine of other species.


Environmental Contamination and Viral Shedding in MERS Patients


BK 3101: COVID-19-Infektion des HNO-Arztes ist Berufskrankheit, kein Arbeitsunfall


title: Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A review

text: Abstract Ethnopharmacological relevance Houttuynia cordata Thunb. (Family: Saururaceae) is an herbaceous perennial plant that grows in moist and shady places. The plant is well known among the people of diverse cultures across Japan, Korea, China and North-East India for its medicinal properties. Traditionally the plant is used for its various beneficial properties against inflammation, pneumonia, severe acute respiratory syndrome, muscular sprain, stomach ulcer etc. Oxidative stress and inflammation were found to be linked with most of the diseases in recent times. Many ancient texts from Chinese Traditional Medicine, Ayurveda and Siddha, and Japanese Traditional medicine have documented the efficacy of H. cordata against oxidative stress and inflammation. Aim of the study This review aims to provide up-to-date and comprehensive information on the efficacy of H. cordata extracts as well as its bioactive compounds both in vitro and in vivo, against oxidative stress and inflammation Materials and methods Relevant information on H. cordata against oxidative stress and inflammation were collected from the established scientific databases such as NCBI, Web of Science, ScienceDirect, Elsevier, and Springer. Additionally, a few books and magazines were also consulted to get the important information. Results Herbal medicines or plant products were traditionally being used for treating the oxidative stress and inflammation related diseases in diverse communities across the world. Scientifically, H. cordata has shown to target several signaling pathways and found to effectively reduce the oxidative stress and inflammation. Phyto-constituents such as afzelin, hyperoside and quercitrin have shown to reduce inflammation both in vitro and in vivo models. These molecules were also shown to have strong antioxidant properties both in vivo and in vitro models. Conclusions H. cordata extracts and its bioactive molecules were shown to have both anti-inflammatory and anti-oxidative properties. As both in vitro and in vivo studies were shown that H. cordata did not have any toxicity on the various model systems used, future clinical studies will hopefully make an impact on the future direction of treating inflammation-related diseases.


title: Virus-like particles associated with porcine epidemic diarrhoea

text: Porcine epidemic diarrhoea type II was reproduced in experimental pigs of various ages by oral dosing with minced intestine from a naturally occurring case of the disease. Virus-like particles which probably represent an unidentified coronavirus were seen by electron microscopy in the faeces and intestinal epithelium of infected animals.


title: Detection and pathogenicity of human metapneumovirus respiratory infection in pediatric Italian patients during a winter–spring season

text: Abstract Background Some diagnostic, epidemiological and clinical features of the recently discovered human metapneumovirus remain to be investigated. Objectives To study the best approach for the diagnosis of human metapneumovirus infections by both conventional and molecular methods, along with the human metapneumovirus circulation rate in northern Italy and the severity of human metapneumovirus respiratory infections in a pediatric patient population. Study design Nasopharyngeal aspirates (NPA) were taken from 306 pediatric patients during the winter–spring season 2003–2004, and examined for conventional respiratory viruses by direct fluorescent staining and cell culture, while human coronavirus and human metapneumovirus were sought by RT-PCR. Results RT-PCR detected human metapneumovirus in 40/306 (13.1%) children positive for respiratory viruses, with an incidence intermediate between that of respiratory syncytial virus (58 patients, 18.9%) and that of influenzavirus infections (29 patients, 9.5%). Phylogenetic analysis showed cocirculation of both human metapneumovirus types (A and B) as well as their relevant subtypes (A1–A2 and B1–B2). Clinically, human metapneumovirus was found to be second to human respiratory syncytial virus alone, as a cause of respiratory tract infections, while duration of virus excretion appeared to correlate with severity of infection, and virus load in NPA with the stage of respiratory infection. Conclusion (i) Human metapneumovirus is a major viral pathogen in the Italian pediatric patient population; (ii) the severity of lower respiratory tract infections approaches that of human respiratory syncytial virus; (iii) there are preliminary indications that the duration of virus excretion may reach 2–3 weeks and that the level of viral load in NPA correlates with the clinical stage of human metapneumovirus infection.


title: OC43 strain‐related coronavirus antibodies in different age groups

text: Serum antibodies against human coronavirus OC43 in different age groups were measured by complement fixation (CF), haemagglutination inhibition (HI), radial diffusion haemolysis‐in‐gel (HIG), and solid‐phase radioimmunoassay (RIA) methods. Antigen grown in suckling mouse brain was used in all tests. Results obtained by the CF and HIG tests, and the RIA, were in good agreement with regard to the presence or absence of antibodies. Similar results were also obtained with the HI test if nonspecific haemagglutination inhibitors were first removed by treatment with phospholipase C and only titers of 1:20 or greater were considered positive. Children 6–23 months of age (n = 45) were without measurable coronavirus antibodies in all four assays. A rapid increase in the prevalence of antibodies then occurred in subsequent age groups, and practically all persons 6 years of age or older were found to have OC43 antibodies as measured by the HIG test or the RIA. The mean antibody levels determined by these two methods continued to increase, however, up to the age group of 10–14 years. This increase in antibody levels after the initial antibody incidence plateau may be due to boosting effects caused by related coronavirus strains, since OC43 antigens are known to cross‐react with antibodies induced by other human coronaviruses. Taken together, these data suggest that OC43 virus, or an antigenically related coronavirus strain, is very common in Finland.


title: Hundreds of severe pediatric COVID-19 infections in Wuhan prior to the lockdown

text: Before January 22, 2020, only one pediatric case of COVID-19 was reported in mainland China. However, a retrospective surveillance study identified six children who had been hospitalized for COVID-19 in one of three central Wuhan hospitals between January 7th and January 15th. Given that Wuhan has over 395 other hospitals, there may have been far more severe pediatric cases than reported. There were six and 43 children out of 336 who tested positive for COVID-19 and influenza, respectively among all pediatric admissions during the 9-day period. By using this ratio in a detailed analysis of influenza surveillance data and COVID-19 epidemic dynamics (see Appendix), we estimate that there were 313 [95% CI: 171-520] children hospitalized for COVID-19 in Wuhan during January 7-15, 2020 (Figure). Under an epidemic doubling time of 7.31 days4, we estimate that there were 1105 [95% CI: 592, 1829] cumulative pediatric COVID-19 hospitalizations prior to the January 23rd lockdown, which far surpasses the 425 confirmed cases reported across all age groups, none of which were children under age 15. Children are strikingly absent from COVID-19 reports and limited data suggest that pediatric infections are overwhelmingly mild5. Thus, our estimates for hundreds of severe pediatric cases likely translates to thousands or even tens of thousands of mildly infected children, suggesting that the force of infection from children may be grossly underestimated and the infection fatality rate overestimated from confirmed case counts alone. This highlights the urgent need for more robust surveillance to gauge the true extent and severity of COVID-19 in all ages.


title: Wearable IoT sensor based healthcare system for identifying and controlling chikungunya virus

text: Abstract Chikungunya is a vector borne disease that spreads quickly in geographically affected areas. Its outbreak results in acute illness that may lead to chronic phase. Chikungunya virus (CHV) diagnosis solutions are not easily accessible and affordable in developing countries. Also old approaches are very slow in identifying and controlling the spread of CHV outbreak. The sudden development and advancement of wearable internet of things (IoT) sensors, fog computing, mobile technology, cloud computing and better internet coverage have enhanced the quality of remote healthcare services. IoT assisted fog health monitoring system can be used to identify possibly infected users from CHV in an early phase of their illness so that the outbreak of CHV can be controlled. Fog computing provides many benefits such as low latency, minimum response time, high mobility, enhanced service quality, location awareness and notification service itself at the edge of the network. In this paper, IoT and fog based healthcare system is proposed to identify and control the outbreak of CHV. Fuzzy-C means (FCM) is used to diagnose the possibly infected users and immediately generate diagnostic and emergency alerts to users from fog layer. Furthermore on cloud server, social network analysis (SNA) is used to represent the state of CHV outbreak. Outbreak role index is calculated from SNA graph which represents the probability of any user to receive or spread the infection. It also generates warning alerts to government and healthcare agencies to control the outbreak of CHV in risk prone or infected regions. The experimental results highlight the advantages of using both fog computing and cloud computing services together for achieving network bandwidth efficiency, high quality of service and minimum response time in generation of real time notification as compared to a cloud only model.


docid: jrzpkdra

title: Fine level epitope mapping and conservation analysis of two novel linear B-cell epitopes of the avian infectious bronchitis coronavirus nucleocapsid protein

text: Abstract The nucleocapsid (N) protein of the infectious bronchitis virus (IBV) may play an essential role in the replication and translation of viral RNA. The N protein can also induce high titers of cross-reactive antibodies and cell-mediated immunity, which protects chickens from acute infection. In this study, we generated two monoclonal antibodies (mAbs), designated as 6D10 and 4F10, which were directed against the N protein of IBV using the whole viral particles as immunogens. Both of the mAbs do not cross react with Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV) and subtype H9 avian influenza virus (AIV). After screening a phage display peptide library and peptide scanning, we identified two linear B-cell epitopes that were recognized by the mAbs 6D10 and 4F10, which corresponded to the amino acid sequences 242FGPRTK247 and 195DLIARAAKI203, respectively, in the IBV N protein. Alignments of amino acid sequences from a large number of IBV isolates indicated that the two epitopes, especially 242FGPRTK247, were well conserved among IBV strains. This conclusion was further confirmed by the relationships of 18 heterologous sequences to the 2 mAbs. The novel mAbs and the epitopes identified will be useful for developing diagnostic assays for IBV infections.


title: Isothermal Nucleic Acid Amplification Techniques and Their Use in Bioanalysis

text: Recently, there has been a rapid progress in the development of techniques for isothermal amplification of nucleic acids as an alternative to polymerase chain reaction (PCR). The advantage of these methods is that the nucleic acids amplification can be carried out at constant temperature, unlike PCR, which requires cyclic temperature changes. Moreover, isothermal amplification can be conducted directly in living cells. This review describes the principles of isothermal amplification techniques and demonstrates their high efficiency in designing new highly sensitive detection methods of nucleic acids and enzymes involved in their modifications. The data on successful application of isothermal amplification methods for the analysis of cells and biomolecules with the use of DNA/RNA aptamers are presented.


title: Intervention strategies for emerging viruses: use of antivirals

text: Today, small molecule antiviral drugs are available for the treatment of infections with herpesviruses, HIV, HBV and HCV as well as with influenza viruses. Ribavirin, a broad-spectrum (but aspecific) antiviral, has been approved for the treatment of infections with respiratory syncytial virus, HCV and Lassa virus. Yet, for many other viruses that cause life-threatening infections [most of which are considered emerging and/or neglected] there are no drugs available. Ideally, potent and broad-spectrum (i.e., pan-genus or pan-family virus activity) antiviral drugs should be developed whereby one drug could be used for the treatment of a number of such viral infections. We here review recent evolutions in the search for inhibitors of emerging and neglected RNA viruses.


title: IFN-lambda preferably inhibits PEDV infection of porcine intestinal epithelial cells compared with IFN-alpha

text: Abstract In contrast to type I interferons that target various types of cells and organs, interferon lambda (IFN-L) primarily acts on mucosal epithelial cells and exhibits robust antiviral activity within the mucosal surface. Porcine epidemic diarrhea virus (PEDV), which causes high morbidity and mortality in piglets, is an enteropathogenic coronavirus with economic importance. Here, we demonstrated that both recombinant porcine IFN-L1 (rpIFN-L1) and rpIFN-L3 have powerful antiviral activity against PEDV infection of both Vero E6 cells and the intestinal porcine epithelial cell line J2 (IPEC-J2). Both forms of rpIFN-L inhibited two genotypes of PEDV (strain CV777 of genotype 1 and strain LNCT2 of genotype 2). rpIFN-L1 primarily controlled viral infection in the early stage and had less antiviral activity in IPEC-J2 than in rpIFN-L3 cells infected with PEDV. In addition, rpIFN-L1 exhibited greater antiviral activity against PEDV infection of IPEC-J2 cells than that of porcine IFN-alpha. Consistent with this finding, rpIFN-L1 triggered higher levels of certain antiviral IFN-stimulated genes (ISGs) (ISG15, OASL, and MxA) in IPEC-J2 cells than porcine IFN-alpha. Although IPEC-J2 cells responded to both IFN-alpha and lambda, transcriptional profiling of ISGs (specifically ISG15, OASL, MxA, and IFITMs) differed when induced by either IFN-alpha or rpIFN-L. Therefore, our data provide the experimental evidence that porcine IFN-L suppresses PEDV infection of IPEC-J2 cells, which may offer a promising therapeutic for combating PED in piglets.


title: Hepatitis E Virus Strains in Rabbits and Evidence of a Closely Related Strain in Humans, France

text: Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains’ genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007–2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%–78.2% identical to HEV genotypes 1–4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.


title: Characterization of the nasopharyngeal microbiota in health and during rhinovirus challenge

text: BACKGROUND: The bacterial communities of the nasopharynx play an important role in upper respiratory tract infections (URTIs). Our study represents the first survey of the nasopharynx during a known, controlled viral challenge. We aimed to gain a better understanding of the composition and dynamics of the nasopharyngeal microbiome during viral infection. METHODS: Rhinovirus illnesses were induced by self-inoculation using the finger to nose or eye natural transmission route in ten otherwise healthy young adults. Nasal lavage fluid samples (NLF) samples were collected at specific time points before, during, and following experimental rhinovirus inoculation. Bacterial DNA from each sample (N = 97 from 10 subjects) was subjected to 16S rRNA sequencing by amplifying the V1-V2 hypervariable region followed by sequencing using the 454-FLX platform. RESULTS: This survey of the nasopharyngeal microbiota revealed a highly complex microbial ecosystem. Taxonomic composition varied widely between subjects and between time points of the same subject. We also observed significantly higher diversity in not infected individuals compared to infected individuals. Two genera – Neisseria and Propionibacterium – differed significantly between infected and not infected individuals. Certain phyla, including Firmicutes, Actinobacteria, and Proteobacteria, were detected in all samples. CONCLUSIONS: Our results reveal the complex and diverse nature of the nasopharyngeal microbiota in both healthy and viral-challenged adults. Although some phyla were common to all samples, differences in levels of diversity and selected phyla were detected between infected and uninfected participants. Deeper, species-level metagenomic sequencing in a larger sample is warranted.


title: Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease

text: BACKGROUND: Herpes simplex virus type-1 (HSV-1) has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. METHODS: We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE) that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. RESULTS: 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. CONCLUSION: The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study provides further evidence that HSV-1 causes isolated pneumonitis in the immunocompromised. The study may provide an estimate on the frequency of relevant HSV-1 infection and bacterial agents in outpatients with autoimmune disease.


docid: oexgdswm

title: Novel targeted drugs approved by the NMPA and FDA in 2019


title: Initial CT imaging characters of an imported family cluster of COVID-19

text: Abstract The objective of this report is to better understand the initial CT imaging spectrum and the relationship between clinical characteristics and initial CT imaging features of an imported family cluster cases involving 7 laboratory-confirmed COVID-19 patients. We find that initial CT findings of 4 patients were positive within one week after the onset of symptoms and 1 patient was negative before the onset of symptoms. Two asymptomatic patients had typical CT abnormalities. The initial CT imaging manifestations are mainly peripheral or subpleural ground-glass opacities and ground-glass with consolidation. Our report is of potential guiding value for the initial CT screening of imported familial cluster cases since the imported cases have an identified time of infection.


title: Liver Sinusoidal Endothelial Cell Lectin, LSECtin, Negatively Regulates Hepatic T-Cell Immune Response

text: Background & Aims The liver is an organ with paradoxic immunologic properties and is known for its tolerant microenvironment, which holds important implications for hepatic diseases. The molecular basis for this local immune suppression, however, is poorly understood. In this study, we aimed to determine the role of liver sinusoidal endothelial cell lectin (LSECtin), a recently identified member of the dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) family, in the regulation of hepatic T-cell immune response. Methods The regulation of T-cell effector function by LSECtin was determined by co-stimulated T cells with anti-CD3/CD28 monoclonal antibody and LSECtin protein, or co-culture of T-cell receptor transgenic T cells with mouse LSECs in vitro. We generated LSECtin knockout mice and prepared recombinant LSECtin protein and complementary DNA plasmids to analyze the role of LSECtin in hepatic T-cell immune regulation in vivo. Results We showed that LSECtin specifically recognized activated T cells and negatively regulated their immune responses. In mice with T-cell–mediated acute liver injury, the lack of LSECtin accelerated the disease owing to an increased T-cell immune response, whereas the exogenous administration of recombinant LSECtin protein or plasmid ameliorated the disease via down-regulation of T-cell immunity. Conclusions Our results reveal that LSECtin is a novel regulator of T cells and expose a crucial mechanism for hepatic T-cell immune suppression, perhaps opening up a new approach for treatment of inflammatory diseases in the liver.


title: Respiratory Viral Infections in Transplant and Oncology Patients

text: Respiratory viral infections are a significant cause of morbidity and mortality in the immunocompromised host. In the last two decades, there has been significant advancement in the epidemiology and laboratory diagnosis of respiratory viral infections. In addition, the clinical consequences of many respiratory viruses in the immunocompetent and immunocompromised host continue to be studied. Many therapeutics have also now become available, although their efficacy in transplant recipients remains uncertain. This article describes the current knowledge about respiratory viral infections as it relates to solid organ transplant, hematopoietic stem cell transplant, and oncology settings.


title: Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID‐19) infected patients

text: We explored the relationships between lymphocyte subsets, cytokines, pulmonary inflammation index (PII) and disease evolution in patients with (corona virus disease 2019) COVID‐19. A total of 123 patients with COVID‐19 were divided into mild and severe groups. Lymphocyte subsets and cytokines were detected on the first day of hospital admission and lung computed tomography results were quantified by PII. Difference analysis and correlation analysis were performed on the two groups. A total of 102 mild and 21 severe patients were included in the analysis. There were significant differences in cluster of differentiation 4 (CD4(+ )T), cluster of differentiation 8 (CD8(+ )T), interleukin 6 (IL‐6), interleukin 10 (IL‐10) and PII between the two groups. There were significant positive correlations between CD4(+ )T and CD8(+ )T, IL‐6 and IL‐10 in the mild group (r (2) = 0·694, r ( 2) = 0·633, respectively; P < 0·01). After ‘five‐in‐one’ treatment, all patients were discharged with the exception of the four who died. Higher survival rates occurred in the mild group and in those with IL‐6 within normal values. CD4(+ )T, CD8(+ )T, IL‐6, IL‐10 and PII can be used as indicators of disease evolution, and the PII can be used as an independent indicator for disease progression of COVID‐19.


title: Doxycycline as a potential partner of COVID-19 therapies

text: Coronavirus disease 2019 (COVID-19) is a major public health challenge, and the current antiviral arsenal for treatment is limited, with questionable efficacy. Major efforts are under way for discovery of new effective agents, but the validation of new potential treatments for COVID-19 may take a long time. Therefore, the repurposing of existing drugs for new indications is needed. In this article, we argue for the potential benefits of using doxycycline with either hydroxycholoroquine or other putative agents for COVID-19 treatment, as doxycycline has antiviral and anti-inflammatory activities by dampening the cytokine storm and to prevent lung damage.


To the Lighthouse: Embracing a Grand Challenge for Cancer Education in the Digital Age


Excitement around hydroxychloroquine for treating COVID-19 causes challenges for rheumatology


title: Modeling serological testing to inform relaxation of social distancing for COVID-19 control

text: The value of serological testing to inform the public health response to the SARS-CoV-2 pandemic is debated. Using a transmission model, we examined how serology can be implemented to allow seropositive individuals to resume more normal levels of social interaction while offsetting the risks. We simulated the use of widespread serological testing with realistic assay characteristics, in which seropositive individuals partially restore their social contacts and act as immunological ‘shields’. If social distancing is relaxed by 50% at the same time that quarterly serological screening is initiated, approximately 120,000 deaths could be averted and a quarter of the US population could be released from social distancing in the first year of the epidemic, compared to a scenario without serological testing. This strategy has the potential to substantially flatten the COVID-19 epidemic curve while also allowing a substantial number of individuals to safely return to social and economic interactions.


title: Clinical management and infection control of SARS: Lessons learned

text: Abstract The outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience of the SARS epidemic, focusing on measures taken to identify and isolate patients, prevent the transmission of infection to healthcare workers and develop effective therapies. Lessons learned from the SARS epidemic will be especially important in responding to the current emergence of another highly pathogenic human coronavirus, the agent of Middle East respiratory syndrome (MERS), and to the recently emerging H7N9 influenza A virus in China. This paper forms part of a symposium in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.”


title: Characterization of HCoV-229E fusion core: Implications for structure basis of coronavirus membrane fusion

text: Abstract Human coronavirus 229E (HCoV-229E), a member of group I coronaviruses, has been identified as one of the major viral agents causing respiratory tract diseases in humans for nearly 40 years. However, the detailed molecular mechanism of the membrane fusion mediated by the spike (S) protein of HCoV-229E remains elusive. Here, we report, for the first time, a rationally designed fusion core of HCoV-229E (HR1-SGGRGG-HR2), which was in vitro produced in GST prokaryotic expression system. Multiple lines of experimental data including gel-filtration, chemical cross-linking, and circular diagram (CD) demonstrated that the HCoV-229E fusion core possesses the typical properties of the trimer of coiled-coil heterodimer (six α-helix bundle). 3D structure modeling presents its most-likely structure, similar to those of coronaviruses that have been well-documented. Collectively, HCoV-229E S protein belongs to the type I fusion protein, which is characterized by the existence of two heptad-repeat regions (HR1 and HR2), furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting the membrane fusion, a crucial step of HCoV-229E infection.


title: A novel human coronavirus: Middle East respiratory syndrome human coronavirus

text: In 2012, a novel coronavirus, initially named as human coronavirus EMC (HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus (MERS-CoV), was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death. Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus, including 34 deaths to date. This novel coronavirus is culturable and two complete genome sequences are now available. Furthermore, molecular detection and indirect immunofluorescence assay have been developed. The present paper summarises the limited recent advances of this novel human coronavirus, including its discovery, genomic characterisation and detection.


title: Diverse Functions of Polyamines in Virus Infection

text: As obligate intracellular parasites, viruses rely on host cells for the building blocks of progeny viruses. Metabolites such as amino acids, nucleotides, and lipids are central to viral proteins, genomes, and envelopes, and the availability of these molecules can restrict or promote infection. Polyamines, comprised of putrescine, spermidine, and spermine in mammalian cells, are also critical for virus infection. Polyamines are small, positively charged molecules that function in transcription, translation, and cell cycling. Initial work on the function of polyamines in bacteriophage infection illuminated these molecules as critical to virus infection. In the decades since early virus-polyamine descriptions, work on diverse viruses continues to highlight a role for polyamines in viral processes, including genome packaging and viral enzymatic activity. On the host side, polyamines function in the response to virus infection. Thus, viruses and hosts compete for polyamines, which are a critical resource for both. Pharmacologically targeting polyamines, tipping the balance to favor the host and restrict virus replication, holds significant promise as a broad-spectrum antiviral strategy.


docid: abzpfdcu

title: Nutrition Therapy in Critically Ill Patients with Coronavirus Disease (COVID‐19)

text: In the midst of a worldwide pandemic of the Coronavirus Disease 2019 (COVID‐19), a paucity of data precludes derivation of COVID‐19‐specific recommendations for nutritional therapy. Until more data are available, the focus needs to center on principles of critical care nutrition modified for the constraints of this disease process, i.e., COVID‐19‐relevant recommendations. Delivery of nutritional therapy must include strategies to reduce exposure and spread of the disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone positioning and extracorporeal membrane oxygenation. Clinicians, though, should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. While data extrapolated from experience in Acute Respiratory Distress Syndrome (ARDS) warrants use of fiber additives and probiotic organisms. The lack of demonstrated benefit precludes a recommendation for micronutrient supplementation. Practices which increase exposure or contamination of equipment, such as use of gastric residual volumes as a monitor, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging should be avoided. At all times, strategies for nutritional therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider. This article is protected by copyright. All rights reserved


title: Chemical microarray: a new tool for drug screening and discovery

text: HTS with microtiter plates has been the major tool used in the pharmaceutical industry to explore chemical diversity space and to identify active compounds and pharmacophores for specific biological targets. However, HTS faces a daunting challenge regarding the fast-growing numbers of drug targets arising from genomic and proteomic research, and large chemical libraries generated from high-throughput synthesis. There is an urgent need to find new ways to profile the activity of large numbers of chemicals against hundreds of biological targets in a fast, low-cost fashion. Chemical microarray can rise to this challenge because it has the capability of identifying and evaluating small molecules as potential therapeutic reagents. During the past few years, chemical microarray technology, with different surface chemistries and activation strategies, has generated many successes in the evaluation of chemical–protein interactions, enzyme activity inhibition, target identification, signal pathway elucidation and cell-based functional analysis. The success of chemical microarray technology will provide unprecedented possibilities and capabilities for parallel functional analysis of tremendous amounts of chemical compounds.


title: Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model

text: Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.


title: Parallel problems

text: Our fight against climate change offers useful lessons for tackling the coronavirus


title: Chapter 11 Health effects

text: Abstract There are beneficial as well as harmful aerosols. According to their nature, harmful particles can be classified into three categories: chemically toxic, infectious, and radioactive. In general, there is a relationship between the response and the dose received. A biochemically active particle may contain only a small amount of active agents. In this respect, an inhaled particle simply acts as a carrier that facilitates delivery of deleterious or beneficial components to specific surface areas of lung airways. In view of the tortuous narrow passageways and sharp turns they have to go through, aerosol particles are an effective carrier. As an indication of their effectiveness, about one half of all 3-m particles inhaled through the mouth deposit in the alveolar region.


title: Effects of indole alkaloids from leaf of Alstonia scholaris on post-infectious cough in mice

text: Abstract Ethnopharmacological relevance Leaf of Alstonia scholaris (L.) R. Br. (Apocynaceae), a wide used ethic-medicine in many Asia and Africa counties, has also been recorded as the common traditional Chinese medicine for treatment of illnesses in respiratory system by Dai people. Aim of the study To provide experimental data of clinical adaption of total indole alkaloids (TA) from leaf of A. scholaris for treating post-infectious cough in phase II clinical trial. Materials and methods To model post-infectious cough, all animals except control group were instilled intra-tracheal with lipopolysaccharide (LPS) (80 μg/50 µL/mouse), followed by subsequent exposure to cigarette smoke (CS) for 30 min per day for a total of 30 days. Mice were orally given TA at dose of 10, 25, 50 mg/kg, and four main alkaloids (Sch: scholaricine, Epi: 19-epischolaricine, Val: vallesamine, Pic: picrinine) once daily. Cellular infiltration was assessed in the broncho-alveolar lavage fluid (BALF). Expression of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum was determined, the superoxide dismutase (SOD) activity as well as malondialdehyde (MDA) content in the serum and homogenate were examined. Finally, histopathological examination in the lungs was assessed by H. E. staining. Results After administration of TA and four major alkaloids respectively, the symptoms of cough in mice were obviously attenuated. Total white blood cells (WBC) and neutrophils (NEU) amounts in BALF were reduced obviously and the pathological damage of lung was also attenuated. There was also significant reduction in IL-6, CRP, MDA and a marked improvement in SOD. Conclusions The efficacy of indole alkaloids against post-infectious cough (PIC) was shown in the down-regulation of inflammatory cells, cytokines, and the balance of antioxidants. What's more, the pharmacological effects of TA were better than single indole alkaloid, which might be related to the synergic effect of four major alkaloids.


title: Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating

text: Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H –binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.


title: Simulated Pediatric Resuscitation Use for Personal Protective Equipment Adherence Measurement and Training During the 2009 Influenza (H1N1) Pandemic

text: Article-at-a-Glance Background Previous experience with simulated pediatric cardiac arrests (that is, mock codes) suggests frequent deviation from American Heart Association (AHA) basic and advanced life support algorithms. During highly infectious outbreaks, acute resuscitation scenarios may also increase the risk of insufficient personal protective equipment (PPE) use by health care workers (HCWs). Simulation was used as an educational tool to measure adherence with PPE use and pediatric resuscitation guidelines during simulated cardiopulmonary arrests of 2009 influenza A patients. Methods A retrospective, observational study was performed of 84 HCWs participating in 11 in situ simulations in June 2009. Assessment included (1) PPE adherence, (2) confidence in PPE use, (3) elapsed time to specific resuscitation maneuvers, and (4) deviation from AHA guidelines. Results Observed adherence with PPE use was 61% for eye shields, 81% for filtering facepiece respirators or powered air-purifying respirators, and 87% for gown/gloves. Use of a “gatekeeper” to control access and facilitate donning of PPE was associated with 100% adherence with gown and respirator precautions and improved respirator adherence. All simulations showed deviation from pediatric basic life support protocols. The median time to bag-valve-mask ventilation improved from 4.3 to 2.7minutes with a gatekeeper present. Rapid isolation carts appeared to improve access to necessary PPE. Confidence in PPE use improved from 64% to 85% after the mock code and structured debriefing. Conclusions Large gaps exist in the use of PPE and self-protective behaviors, as well as adherence to resuscitation guidelines, during simulated resuscitation events. Intervention opportunities include use of rapid isolation measures, use of gatekeepers, reinforcement of first responder roles, and further simulation training with PPE.


title: Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3

text: As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.


title: Glycyrrhizic acid derivatives as influenza A/H1N1 virus inhibitors

text: Abstract This Letter describes the synthesis and antiviral activity study of some glycyrrhizic acid (GL) derivatives against influenza A/H1N1/pdm09 virus in MDCK cells. Conjugation of GL with l-amino acids or their methyl esters, and amino sugar (d-galactose amine) dramatically changed its activity. The most active compounds were GL conjugates with aromatic amino acids methyl esters (phenylalanine and tyrosine) (SI=61 and 38), and S-benzyl-cysteine (SI=71). Thus modification of GL is a perspective route in the search of new antivirals, and some of GL derivatives are potent as anti-influenza A/H1N1 agents.


The pathogens


title: Sovereign rating after private and official restructuring

text: This paper studies the relationship between sovereign debt (final) restructuring and sovereign ratings, by distinguishing between commercial and official debt and by considering the creditors’ loss (haircut). Institutional Investor’s index is taken as a measure of a country’s creditworthiness. We find that while a restructuring with private creditors seems to involve some reputational costs, ”official defaulters” are not affected (or may even benefit) by the restructuring episodes. Using the Synthetic Control Method, we find further evidence for the heterogeneity of the economic impact of debt restructurings, confirming that official and private restructurings may have different costs and then induce selective defaults.


title: “Alteración del nivel de conciencia puerperal: ¿puede el covid-19 ser causa de síndrome de encefalopatía posterior reversible?”

text: SUMMARY We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus.Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubationfor decubitus intolerance. After extubation, she presented altered mental statethat required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2.CT and CT-angiography were normal, spinal fluid tests were non-specific, and magnetic resonance imaging reported posterior reversible encephalopathy syndrome (PRES) (due to radiological features suggestive of white matter vasogenic edema affecting the parietal, temporal and occipital lobes, along with altered mental state) secondary to gestational hypertension. Eleven days after the cesarean section the patient began to develop hypertension that required treatment. PRES is associated with certain clinical (headache, altered mental state, visual disturbances and convulsions) and radiological (reversible changes in white substance mainly affecting the parietal, temporal, and occipital lobes) characteristics suggestive of vasogenic oedema In pregnant SARS-CoV-2 patients, the differential diagnosis of hypertension and altered mental state is often extremely complicated because complementary tests can be normal and there is no immediate sign of peripartum hypertension. SARS CoV-2 genome sequencing in spinal fluid could have provided a definitive diagnosis, but the treatment would not have differed.


title: MITA/STING: A central and multifaceted mediator in innate immune response

text: Abstract The recognition of nucleic acids is a general strategy used by the host to detect invading pathogens. Many studies have established that MITA/STING is a central component in the innate immune response to cytosolic DNA and RNA derived from pathogens. MITA can act both as a direct sensor of cyclic dinucleotides (CDNs) and as an adaptor for the recruitment of downstream signaling components. In both roles, MITA is part of signaling cascades that orchestrate innate immune defenses against various pathogens, including viruses, bacteria and parasites. Here, we highlight recent studies that have uncovered the molecular mechanisms of MITA-mediated signal transduction and regulation, and discuss some notable issues that remain elusive.


docid: uxrmcprp

title: Virulent Epidemics and Scope of Healthcare Workers' Duty of Care

text: The phrase "duty of care" is, at best, too vague and, at worst, ethically dangerous. The nature and scope of the duty need to be determined, and conflicting duties must be recognized and acknowledged. Duty of care is neither fixed nor absolute but heavily dependent on context. The normal risk level of the working environment, the healthcare worker's specialty, the likely harm and benefits of treatment, and the competing obligations deriving from the worker's multiple roles will all influence the limits of the duty of care. As experts anticipate the arrival of an avian influenza pandemic in humans, discussion of this matter is urgently needed.


title: AAV Vectors Vaccines Against Infectious Diseases

text: Since their discovery as a tool for gene transfer, vectors derived from the adeno-associated virus (AAV) have been used for gene therapy applications and attracted scientist to this field for their exceptional properties of efficiency of in vivo gene transfer and the level and duration of transgene expression. For many years, AAVs have been considered as low immunogenic vectors due to their ability to induce long-term expression of non-self-proteins in contrast to what has been observed with other viral vectors, such as adenovirus, for which strong immune responses against the same transgene products were documented. The perceived low immunogenicity likely explains why the use of AAV vectors for vaccination was not seriously considered before the early 2000s. Indeed, while analyses conducted using a variety of transgenes and animal species slowly changed the vision of immunological properties of AAVs, an increasing number of studies were also performed in the field of vaccination. Even if the comparison with other modes of vaccination was not systemically performed, the analyses conducted so far in the field of active immunotherapy strongly suggest that AAVs possess some interesting features to be used as tools to produce an efficient and sustained antibody response. In addition, recent studies also highlighted the potential of AAVs for passive immunotherapy. This review summarizes the main studies conducted to evaluate the potential of AAV vectors for vaccination against infectious agents and discusses their advantages and drawbacks. Altogether, the variety of studies conducted in this field contributes to the understanding of the immunological properties of this versatile virus and to the definition of its possible future applications.


title: RNA interference against viruses: strike and counterstrike

text: RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid–based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials. Although induced RNAi is able to trigger profound and specific inhibition of virus replication, it is becoming clear that RNAi therapeutics are not as straightforward as we had initially hoped. Difficulties concerning toxicity and delivery to the right cells that earlier hampered the development of antisense-based therapeutics may also apply to RNAi. In addition, there are indications that viruses have evolved ways to escape from RNAi. Proper consideration of all of these issues will be necessary in the design of RNAi-based therapeutics for successful clinical intervention of human pathogenic viruses.


docid: cgdlhpvb

title: Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes

text: Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.


Reply to Guglielmo Mantica, Nazareno Suardi, and Carlo Terrone’s Letter to the Editor re: Ming-Chun Chan, Sharon E.K. Yeo, Yew-Lam Chong, Yee-Mun Lee. Stepping Forward: Urologists’ Efforts During the COVID-19 Outbreak in Singapore. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.03.004


Transmission catalog proposed to help combat zoonotic diseases


title: COVID-19: hypofractionation in the Radiation Oncology Department during the ‘state of alarm’: first 100 patients in a private hospital in Spain

text: During the COVID-19 pandemic, Spain declared a ‘state of alarm’ on 14 March 2020. In our Radiation Oncology Department, experienced in administering hypofractionated treatments (partial irradiation in breast cancer, moderate hypofractionation in localized prostate cancer, etc), we have increased the hypofractionated treatment indications. We are only deferring the start of non-urgent treatments such as prostate tumours under androgen deprivation or benign brain tumours which are candidates for radiosurgery such as meningiomas or acoustic neuroma. In this hypofractionation era we find that we have decreased the number of sessions per patient and that we can evaluate the last years with the fractionation index (FI) (calculated by dividing the total number of fractions administered in the department by the total number of patients treated). We have gone from 14.4 in 2018 to 13.78 in 2019, excluding brachytherapy. We report the results of the first 100 patients who have experienced radiotherapy treatment since the state of alarm (66 women and 34 men). In these patients, the FI is 12.12—lower than previous years.


title: Infiltración con onabotulinumtoxinA y bloqueos en el paciente con cefalea y neuralgia: recomendaciones de seguridad frente a la infección por SARS-CoV-2

text: INTRODUCTION: The COVID-19 pandemic has given rise to the need for changes in clinical practice, with new strategies to enable integrated care for patients with headache and neuralgia. MATERIAL AND METHODS: Given the high spreadability of SARS-CoV-2, new safety measures are required in such procedures as onabotulinumtoxinA infiltration and nerve blocks. RESULTS: We present a series of recommendations based on the measures implemented to prevent infection in our healthcare system. We differentiate between measures related to patients and physicians, to technique, to infrastructure (waiting room and consultation), and to healthcare management.


title: Demystifying pulmonary vascular complications in severe coronavirus disease-19 pneumonia (COVID-19) in the light of clinico-radiologic-pathologic correlation

text: • Small pulmonary vessel changes are a unique imaging feature of COVID-19 pneumonia. • Autopsy studies reveal a very high incidence of peripheral pulmonary thrombosis. • Risk of thrombosis is high in severe COVID-19 despite anticoagulation. • Mounting evidence suggests immunothrombosis as a contributory cause of thrombosis. • Combined inflammation reduction and anticoagulation seems to be a rational therapeutic protocol.


title: Static All-Atom Energetic Mappings of the SARS-Cov-2 Spike Protein with Potential Latch Identification of the Down State Protomer

text: The SARS-Cov-2 virion responsible for the current world-wide pandemic Covid-19 has a characteristic Spike protein (S) on its surface that embellishes both a prefusion state and fusion state. The prefusion Spike protein (S) is a large trimeric protein where each protomer may be in a so-called Up state or Down state, depending on the configuration of its receptor binding domain (RBD). The Up state is believed to allow binding of the virion to ACE-2 receptors on human epithelial cells, whereas the Down state is believed to be relatively inactive or reduced in its binding behavior. We have performed detailed all-atom, dominant energy landscape mappings for noncovalent interactions (charge, partial charge, and van der Waals) of the SARS-Cov-2 Spike protein in its static prefusion state based on recent structural information. We included both interchain interactions and intrachain (domain) interactions in our mappings in order to determine any telling differences (different so-called “glue” points or “hot spots”) between residues in the Up and Down state protomers. In general, the S2 or fusion machinery domain of S is relatively rigid with strong noncovalent interactions facilitated by helical secondary structures, whereas the S1 domain, which contains the RBD and N-terminal domain (NTD), is relatively more flexible and characterized by beta strand structural motifs. The S2 domain demonstrated no appreciable energetic differences between Up and Down protomers, including interchain as well as each protomer’s intrachain, S1–S2 interactions. However, the S1 domain interactions across neighboring protomers, which include the RBD-NTD cross chain interactions, showed energetic differences between Up-Down and Down-Down neighboring protomers. Surprisingly, the Up-Down, RBD-NTD interactions were overall stronger and more numerous than the Down-Down cross chain interactions, including the appearance of the three residue sequence ALA520-PRO521-ALA522 associated with a turn structure in the RBD of the Up state. Additionally, our intrachain dominant energy mappings within each protomer, identified a significant “glue” point or possible latch for the Down state protomer between the S1 subdomain, SD1 and the RBD domain of the same protomer that was completely missing in the Up state protomer analysis. Ironically, this dominant energetic interaction in the Down state protomer involved the backbone atoms of the same three residue sequence ALA520-PRO521-ALA522 of the RBD with the R-group of GLN564 in the SD1 domain. Thus, this same three residue sequence acts as a stabilizer of the RBD in the Up conformation through its interactions with its neighboring NTD chain and a kind of latch in the Down state conformation through its interactions with its own SD1 domain. The dominant interaction energy residues identified here are also conserved across reported variations of SARS-Cov-2, as well as the closely related virions SARS-Cov and the bat corona virus RatG13. However, these results are all based on static structure analysis and large scale dynamic simulations will be necessary to further investigate these findings. Nonetheless, static dominant energy landscape mappings represents a starting point for more detailed dynamic analyses and hopefully an improved understanding at the structure-function relationship of this highly complex protein.


title: Cholesterol: fa(s)t-food for enterovirus genome replication

text: Hijacking and remodeling of host membranes is an obligatory step in the replicative cycle of (+)RNA viruses, including enteroviruses. Ilnytska et al. unveiled in Cell Host & Microbe that enteroviruses usurp clathrin-mediated endocytosis to shuttle cholesterol to sites of genome replication and that cholesterol is needed for efficient replication.


title: Chloroquine interferes with dengue‐2 virus replication in U937 cells

text: The objective of this study was to investigate the use of chloroquine (CLQ) as an antiviral agent against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of U937 cells infected with dengue virus type 2 (DENV‐2). Viral replication was assessed by quantification of virus produced through detection of copy numbers of DENV‐2 RNA, plaque assay and indirect immunofluorescence. qRT‐PCR and plaque assays were used to quantify the DENV‐2 load in infected U937 cells after CLQ treatment. It was found that a dose of 50 μg/mL of CLQ was not toxic to the cells and resulted in significantly less virus production in infected U937 cells than occurred in untreated cells. In the present work, CLQ was effective against DENV‐2 replication in U937 cells, and also caused a statistically significant reduction in expression of proinflammatory cytokines. The present study indicates that CLQ may be used to reduce viral yield in U937 cells.


title: Review of the present features and the infection control challenges of COVID‐19 pandemic in dialysis facilities

text: The COVID‐19 has swept the world causing suffering, death, loss, and massive economy damage. The dialysis population is vulnerable and the dialysis facility is critical in maintaining operations and avoiding disease transmission. The present information regarding the clinical features of COVID‐19 infection in the dialysis population was collected, and the useful measures of COVID‐19 infection prevention and infection control in the dialysis facilities were summarized. Leadership, education, preparedness, management, and recovery phase were determined to be the critical procedures. It is hoped this updated interim review might provide information for medical professionals to take proactive action to best prepare and mitigate damage when facing the COVID‐19 pandemic challenge.


title: COVID-19 and Italy: what next?

text: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. A global response to prepare health systems worldwide is imperative. Although containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, and Italy has been particularly affected. There is now grave concern regarding the Italian national health system's capacity to effectively respond to the needs of patients who are infected and require intensive care for SARS-CoV-2 pneumonia. The percentage of patients in intensive care reported daily in Italy between March 1 and March 11, 2020, has consistently been between 9% and 11% of patients who are actively infected. The number of patients infected since Feb 21 in Italy closely follows an exponential trend. If this trend continues for 1 more week, there will be 30 000 infected patients. Intensive care units will then be at maximum capacity; up to 4000 hospital beds will be needed by mid-April, 2020. Our analysis might help political leaders and health authorities to allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. If the Italian outbreak follows a similar trend as in Hubei province, China, the number of newly infected patients could start to decrease within 3–4 days, departing from the exponential trend. However, this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in China.


title: Determining the Optimal Outcome Measures for Studying the Social Determinants of Health

text: Americans have significantly poorer health outcomes and shorter longevity than citizens of other industrialized nations. Poverty is a major driver of these poor health outcomes in the United States. Innovative anti-poverty policies may help reduce economic malaise thereby increasing the health and longevity of the most vulnerable Americans. However, there is no consensus framework for studying the health impacts of anti-poverty social policies. In this paper, we describe a case study in which leading global experts systematically: (1) developed a conceptual model that outlines the potential pathways through which a social policy influences health, (2) fits outcome measures to this conceptual model, and (3) estimates an optimal time frame for collection of the selected outcome measures. This systematic process, called the Delphi method, has the potential to produce estimates more quickly and with less bias than might be achieved through expert panel discussions alone. Our case study is a multi-component randomized-controlled trial (RCT) of a workforce policy called MyGoals for Healthy Aging.


title: A Case of Novel Corona Virus With Three Negative Nasopharyngeal Swabbings

text: We hereby report a case of a 55-year-old male with fever and difficulty breathing over several days who treated for presumed COVID-19 pneumonia despite testing negative thrice via reverse transcription polymerase chain reaction (RT-PCR) nasal swab. We explore several possible reasons for serially negative SARS-CoV-2 testing and other potential avenues of diagnosis.


Viral Community-Acquired Pneumonia If We Do Not Diagnose It and Do Not Treat It, Can It Still Hurt Us?


title: Selection of a candidate probiotic strain of Pediococcus pentosaceus from the faecal microbiota of horses by in vitro testing and health claims in a mouse model of Salmonella infection

text: AIMS: The aim of this study was to verify the suitable use of candidate ‘probiotics’ selected by in vitro tests and the importance of in vivo assays to nominate micro‐organisms as probiotics and alternative prophylactic treatments for Salmonella Typhimurium infection. METHODS AND RESULTS: Thirty‐three lactic acid bacteria (LAB) isolated from foal's faeces were assessed based on the main desirable functional in vitro criteria. Based on these results, Pediococcus pentosaceus strain 40 was chosen to evaluate its putative probiotic features in a mouse model of Salmonella infection. Daily intragastric doses of Ped. pentosaceus 40 for 10 days before and 10 days after Salmonella challenge (10(6) CFU of Salm. Typhimurium per mouse) led to a significant aggravation in mouse health by increasing weight loss, worsening clinical symptoms and anticipating the time and the number of deaths by Salmonella. Pediococcus pentosaceus modulated cell‐mediated immune responses by up‐regulation of the gene expression of the proinflammatory cytokines IFN‐γ and TNF‐α in the small intestine. CONCLUSION: The usual criteria were used for in vitro screening of a large number of LAB for desirable probiotic functional properties. However, the best candidate probiotic strain identified, Ped. pentosaceus #40, aggravated the experimental disease in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings emphasize the need for prophylactic or therapeutic effectiveness to be demonstrated in in vivo models to make precise health claims.


title: Two decades of vaccine innovations for global public good: Report of the Developing Countries’ Vaccine Manufacturers Network 20th meeting, 21–23 october 2019, Rio de Janeiro, Brazil

text: The Developing Countries’ Vaccine Manufacturers Network, joined by global health organizations, held its 20th meeting celebrating two decades of vaccine innovations for global public good. Health leaders from industry, academia and global health organizations reviewed efforts to accelerate innovation, improve access to vaccines, overcome inequalities and strengthen technological and public-health management capabilities. Discussion topics included World Health Organization’s immunization strategy, Pan American Health Organization’s system-strengthening efforts, Gavi’s evaluation of vaccine coverage in middle income countries and developments on public-market intelligence. Health market trends, delivery gaps, integration of system-wide needs, costs and benefits, and implications for stakeholder decision-making were areas of focus. Novel thinking was discussed on integration of policy, financing, regulatory pathways and alignment of innovation priorities to improve efficiency in vaccine development pathways. The Vaccine Innovation Prioritization Strategy collaboration presented nine global innovation priorities, and many other partners and members presented updates on their priorities. Novel technologies and platforms, such as RNA-based vaccines, adenoviral vectors, bioconjugation, blow-fill-seal and two-dimensional barcodes, provided opportunities to accelerate vaccine innovations. Challenges in planning and operations at global level included those in health security, polio eradication, re-emergence of diseases, disparities between forecasts and orders and heterogeneous regulatory requirements. Manufacturers were urged to accelerate innovation and prequalification of high-impact vaccines, such as pneumococcal, human papillomavirus and rotavirus vaccines, to strengthen immunization globally.


Pancreatic injury patterns in patients with COVID-19 pneumonia


Two Epidemics and Global Health Security Agenda


title: Clinical and Molecular Epidemiology of Human Bocavirus in Respiratory and Fecal Samples from Children in Hong Kong

text: Background. Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory tract infections in children. We conducted the first systematic prospective clinical and molecular study using nasopharyngeal aspirates (NPAs) and fecal samples. Methods. NPAs negative for influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, and coronavirus and fecal samples from patients with acute gastroenteritis were included. On the basis of results from a pilot study using 400 NPAs from all age groups, a prospective 12-month study was conducted to detect HBoV in 1200 NPAs and 1435 fecal samples from patients <18 years old by polymerase chain reaction. The complete genome sequences of HBoVs from 12 NPAs and 12 fecal samples were determined. Results. Of the 400 NPAs collected in the pilot study, 20 (5.0%) were found to contain HBoV, all from children <5 years old. In the subsequent prospective study of pediatric patients, HBoV was detected in 83 (6.9%) of 1200 NPAs. Upper and lower respiratory tract infections were equally common. HBoV was detected in 30 (2.1%) of 1435 fecal samples. Fever and watery diarrhea were the most common symptoms. The seasonality of HBoV in NPAs and fecal samples was similar. Codetection with other pathogens occurred in 33% and 56% of NPAs and fecal samples, respectively, from patients with HBoV infection. Genomes of HBoVs from NPAs and fecal samples displayed minimal sequence variations. Conclusions. HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections.


title: Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection

text: Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs) for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IIF). Through IIF, 33 (20.4%) specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3%) positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV). Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1) pdm09 virus, human coronavirus (HCoV) NL63 and HCoV HKU1].


title: A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus

text: A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.


title: Coat protein expression strategy of oat blue dwarf virus

text: Abstract Oat blue dwarf virus (OBDV) is a member of the genus Marafivirus whose genome encodes a 227kDa polyprotein (p227) ostensibly processed post-translationally into its functional components. Encoded near the 3' terminus and coterminal with the p227 ORF are ORFs specifying major and minor capsid proteins (CP). Since the CP expression strategy of marafiviruses has not been thoroughly investigated, we produced a series of point mutants in the OBDV CP encoding gene and examined expression in protoplasts. Results support a model in which the 21kDa major CP is the product of direct translation of a sgRNA, while the 24kDa minor CP is a cleavage product derived from both the polyprotein and a larger ~26kDa precursor translated directly from the sgRNA. Cleavage occurs at an LXG[G/A] motif conserved in many viruses that use papain-like proteases for polyprotein processing and protection against degradation via the ubiquitin-proteasome system.


title: Global toxocariasis research trends from 1932 to 2015: a bibliometric analysis

text: BACKGROUND: Toxocariasis is a highly prevalent parasitic disease in the tropical regions of the world, with its impact on public health being typically underestimated. To better recognise the trends and characteristics of toxocariasis research, this study is a bibliometric analysis of the global toxocariasis research. METHODS: Searches were completed on April 5, 2016, using the Scopus database. A search without any language restriction was performed to extract publications dealing with toxocariasis. Terms related to toxocariasis were used to perform a title keyword search. RESULTS: A total of 2765 publications comprising 11 document types and published between 1932 and 2015 were included in the analysis. Articles were the most popular document form, accounting for 83.62% of all publications, followed by letters (3.80%) and reviews (3.4%). The annual number of research publications increased from 30 in 1980 to 111 in 2015, indicating that the number of publications on toxocariasis has increased slowly over the past 35 years. The United States of America and Japan are the predominant countries of origin, with 303 articles and 207 articles, respectively, followed by Brazil and the United Kingdom, with 180 (6.5%) each. The h-index for all the publications was 60. The highest h-index were for publications from the United Kingdom (h-index value = 43) and the United States (h-index value = 39); these two countries were also involved with the highest number of international collaborations, with 27 and 28 countries, respectively. CONCLUSIONS: Developed countries, including the United States, Japan, the United Kingdom, France, Germany and Italy, are the world’s leaders in toxocariasis research, contributing to more than 34% of the total published literature. In addition, developing countries, such as Brazil, Poland, Argentina and India, showed a noticeable increase in published papers on toxocariasis research in recent years. A push for more collaboration is needed to achieve a superior research strategy related to toxocariasis at the global level from the viewpoint of epidemiological data, clinical aspects, medical ecology, molecular aspects and treatment practices associated with toxocariasis.


title: Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society

text: Not needed.


JEPM April 2020 – Avian & Exotic News


title: Coalition for medical education—A call to action: A proposition to adapt clinical medical education to meet the needs of students and other healthcare learners during COVID‐19

text: With the ongoing coronavirus, journals and the media have extensively covered the impacts on doctors, nurses, physician assistants, and other healthcare workers. However, one group that has rarely been mentioned despite being significantly impacted is medical students and medical education overall. This piece, prepared by both a medical student and a cardiothoracic surgeon with a long career in academic medicine, discusses the recent history of medical education and how it has led to issues now with distance‐based learning due to COVID‐19. It concludes with a call to action for the medical education system to adapt so it can meet the needs of healthcare learners during COVID‐19 and even beyond.


title: Molecular Diagnosis of Severe Acute Respiratory Syndrome

text: The etiologic agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, known as SARS-coronavirus (SARS-CoV). Although the SARS epidemic has subsided, many authorities, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), have warned of the possible re-emergence of this highly infectious disease. Although antibody-based diagnosis of SARS has been demonstrated to be a reliable proof of SARS infection, it is not sensitive enough for detection during the early phase of the disease. To date, based on the publicly released full genomic sequences of SARS-CoV, various molecular detection methods based on reverse-transcription polymerase chain reaction (RT-PCR) have been developed. Although most of the assays have initially been focused on RNA extracted from nasopharyngeal aspirates, urine, and stools, several of the more recently developed assays have been based on the analysis of RNA extracted from plasma and serum. Such assays allow the more standardized quantitative expression of viral loads and are potentially useful for early SARS diagnosis. In this chapter, two real-time quantitative RT-PCR systems for the quantification of SARS-CoV RNA in serum are discussed. The two RT-PCR systems, one aimed toward the nucleocapsid region and the other toward the polymerase region of the virus genome, have a detection rate of up to 80% during the first week of illness. These quantitative systems are potentially useful for the early diagnosis of SARS and can also provide viral load information that might assist clinicians in making a prognostic evaluation of an infected individual.


title: Mitophagy in TGEV infection counteracts oxidative stress and apoptosis

text: The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.


title: Improved synthesis of rupintrivir

text: An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (l-glutamic acid, d-4-fluorophenylalanine, and l-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.