title: False positive antibody results against human T‐cell lymphotropic virus in patients with severe acute respiratory syndrome

text: Taiwan suffered from the outbreak of severe acute respiratory syndrome (SARS) in 2003. Our laboratory performed a series of virology and serology tests for SARS patients admitted to our hospital. Cross‐reactivity was found when testing for antibody against human T‐cell lymphotropic virus (HTLV) in one patient with SARS. Therefore, antibodies against HTLV were examined in paired‐sera from 26 SARS patients. ELISA and a neutralization test were used to measure anti‐SARS antibodies. Seroconversion for antibody against SARS‐CoV was observed in all patients. Surprisingly, with the use of ELISA for HTLV, sera for 13 patients were positive for HTLV (50%), and seroconversion for HTLV was also observed in 10 patients (38.5%). Western blot for HTLV on those 26 paired‐sera from 13 HTLV‐positive patients displayed 5 positive results for HTLV‐I, 7 positive results for HTLV‐II, 1 positive result for both HTLV‐I and II, 9 negative results for either HTLV‐I or HTLV‐II, and 4 “indeterminate” results. The findings that antibody to HTLV can be detected in blood samples collected from SARS patients provide important information for safe handling of blood products. Without such knowledge, blood products can be discarded mistakenly even though they contain anti‐SARS‐CoV antibodies that may be potentially valuable for SARS therapy. J. Med. Virol. 77:331–336, 2005. © 2005 Wiley‐Liss, inc.


title: Genomic characterization and pathogenicity of porcine deltacoronavirus strain CHN-HG-2017 from China

text: Porcine deltacoronavirus (PDCoV) was first detected in Hong Kong and has recently spread to many countries around the world. PDCoV causes acute diarrhea and vomiting in pigs, resulting in significant economic losses in the global pork industry. In this study, a Chinese PDCoV strain, designated CHN-HG-2017, was isolated from feces of a suckling piglet with severe watery diarrhea on a farm located in central China. Subsequently, the virus was identified by an indirect immunofluorescence assay and electron microscopy. A nucleotide sequence alignment showed that the whole genome of CHN-HG-2017 is 97.6%-99.1% identical to other PDCoV strains. Analysis of potential recombination sites showed that CHN-HG-2017 is a possible recombinant originating from the strains CH/SXD1/2015 and Vietnam/HaNoi6/2015. Furthermore, the pathogenicity of this recombinant PDCoV strain was investigated in 5-day-old piglets by oral inoculation. The challenged piglets developed typical symptoms, such as vomiting, anorexia, diarrhea and lethargy, from 1 to 7 days post-inoculation (DPI). Viral shedding was detected in rectal swabs until 14 DPI in the challenged piglets. Interestingly, high titers of virus-neutralizing antibodies in sera were detected at 21 DPI. Tissues of small intestines from CHN-HG-2017-infected piglets at 4 DPI displayed significant macroscopic and microscopic lesions with clear viral antigen expression. Our analysis of the full genome sequence of a recombinant PDCoV and its virulence in suckling piglets might provide new insights into the pathogenesis of PDCoV and facilitate further investigation of this newly emerged pathogen.


title: Correlation Between Abnormal Platelet Count and Respiratory Viral Infection in Patients From Cheonan, Korea

text: BACKGROUND: In this study, the effects of viral infections on platelet (PLT) count have been reported. This study examined the correlation between PLT count and respiratory virus (RV) infections. METHODS: Patients who visited Dankook University Hospital between December 2006 and February 2014 with symptoms of suspected RV infection were recruited. Multiplex reverse transcriptase polymerase chain reactions identified the causative virus(es). PLT counts were analyzed with respect to virus, age and sex of the patient, and length of hospital stay. RESULTS: Of the 8,147 patients, 62.8% were RV‐positive, and 18.6% of RV‐positive patients had abnormal PLT counts. There were no differences in the rates of abnormal PLT counts between single‐infection and virus co‐infection cases. In RV infection patients, the incidence of abnormal PLT count increased with age and varied depending on the RV infection type. Patients with abnormal PLT count stayed in hospital longer than those with normal PLT count. CONCLUSIONS: The incidence of thrombocytopenia was higher among the elderly; in younger patients, thrombocytosis was more prevalent than thrombocytopenia. Respiratory tract infections caused by different viruses resulted in varied PLT count changes. Further systematic research of PLT count changes related to viral infections is required.


title: Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011

text: BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.


docid: cngpsxcs

title: Interventions to Mitigate Emergency Department and Hospital Crowding During an Infectious Respiratory Disease Outbreak: Results from an Expert Panel

text: Objective: To identify and prioritize potential Emergency Department (ED) and hospital-based interventions which could mitigate the impact of crowding during patient surge from a widespread infectious respiratory disease outbreak and determine potential data sources that may be useful for triggering decisions to implement these high priority interventions. Design: Expert panel utilizing Nominal Group Technique to identify and prioritize interventions, and in addition, determine appropriate “triggers” for implementation of the high priority interventions in the context of four different infectious respiratory disease scenarios that vary by patient volumes (high versus low) and illness severity (high versus low). Setting: One day in-person conference held November, 2011. Participants: Regional and national experts representing the fields of public health, disease surveillance, clinical medicine, ED operations, and hospital operations. Main Outcome Measure: Prioritized list of potential interventions to reduce ED and hospital crowding, respectively. In addition, we created a prioritized list of potential data sources which could be useful to trigger interventions. Results: High priority interventions to mitigate ED surge included standardizing admission and discharge criteria and instituting infection control measures. To mitigate hospital crowding, panelists prioritized mandatory vaccination and an algorithm for antiviral use. Data sources identified for triggering implementation of these interventions were most commonly ED and hospital utilization metrics. Conclusions: We developed a prioritized list of potentially useful interventions to mitigate ED and hospital crowding in various outbreak scenarios. The data sources identified to “trigger” the implementation of these high priority interventions consist mainly of sources available at the local, institutional level.


title: A virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors

text: Abstract Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)-negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences. ViroCap is a targeted capture and next generation sequencing tool that was designed to identify all known vertebrate DNA and RNA viruses. In this study we used a metagenomic approach using ViroCap for DNA viruses in 20 FOSCC, 9 normal feline oral mucosal, and 8 suspected PV positive control samples. We tested the hypothesis that viruses would be enriched in FOSCC compared to normal oral mucosa. The virome of the FOSCC and normal feline oral mucosa consisted of feline foamy virus in 7/20 and 2/9 (35% and 22%), feline torque teno virus in 2/20 and 0/9 (10% and 0%), alphaherpesvirus in 2/10 and 0/9 (10% and 0%), FIV (0% and 22%), Epstein-Barr virus in 1/20 and 0/9 (5% and 0%) and feline papillomavirus in 1/20 and 0/9 samples (5% and 0% respectively). Felis catus papillomavirus-3 was found in 1 of 20 FOSCC samples. A virus was not associated consistently with FOSCC. If PVs have a role in FOSCC it is at most a supplementary or uncommon role. FOSCC appears most closely related to HPV-negative HNSCC. Future research on FOSCC should focus on identifying genetic and environmental causes.


docid: ycztzrat

title: Chapter 11 Solid and Suspension Microarrays for Microbial Diagnostics

text: Abstract Advancements in molecular technologies have provided new platforms that are being increasingly adopted for use in the clinical microbiology laboratory. Among these, microarray methods are particularly well suited for diagnostics as they allow multiplexing, or the ability to test for multiple targets simultaneously from the same specimen. Microarray technologies commonly used for the detection and identification of microbial targets include solid-state microarrays, electronic microarrays and bead suspension microarrays. Microarray methods have been applied to microbial detection, genotyping and antimicrobial resistance gene detection. Microarrays can offer a panel approach to diagnose specific patient presentations, such as respiratory or gastrointestinal infections, and can discriminate isolates by genotype for tracking epidemiology and outbreak investigations. And, as more information has become available on specific genes and pathways involved in antimicrobial resistance, we are beginning to be able to predict susceptibility patterns based on sequence detection for particular organisms. With further advances in automated microarray processing methods and genotype–phenotype prediction algorithms, these tests will become even more useful as an adjunct or replacement for conventional antimicrobial susceptibility testing, allowing for more rapid selection of targeted therapy for infectious diseases.


title: Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus

text: The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.


title: Untersuchungen zur Virusätiologie der Nasopharynxkarzinome

text: Five carcinoma of the nasopharynx (four lymphoepithelial carcinoma of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact. The following structures were found: 1. Particles and microtubules which correspond in diameter, shape and location to Corona viruses. 2. Particles surrounded by a double membrane and resembling in form and diameter Onkorna viruses. 3. Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack. 4. Spherical nuclear bodies, which are frequently observed in tumors and during viral infections. 5. Intranuclear particles which correspond in diameter, structure and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure. Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors.


title: 3D-printed face protective shield in interventional radiology: evaluation of an immediate solution in the era of COVID-19 pandemic

text: Abstract Purpose: The purpose of this study was to report the clinical evaluation of a 3D-printed protective face shield designed to protect interventional radiologists from droplet transmission of the SARS-Cov-2. Materials and methods: A protective face shield consisting in a standard transparent polymerizing vinyl chloride (PVC) sheet was built using commercially available 3D printers. The 3D-printed face shield was evaluated in 31 interventional procedures in terms of ability to perform the assigned intervention as usual, quality of visual comfort and tolerance using a Likert scale (from 1, as very good to 5, as extremely poor). Results: The mean rating for ability to perform the assigned intervention as usual was 1.7 ± 0.8 (SD) (range: 1 - 4). The mean visual tolerance rating was 1.6 ± 0.7 (SD) (range: 1 - 4). The mean tolerability rating was 1.4 ± 0.7 (SD) (range: 1 - 3). Conclusion: The 3D-printed protective face shield is well accepted in various interventions. It may become an additional option for protection of interventional radiologists.


title: Current Disease and Epidemiologic Problems: What’s Hot?

text: Included among the many current world problems are viral diseases of considerable significance and threat. This talk could not possible cover them all but will discuss the emergence of Middle East respiratory syndrome in Saudi Arabia and nearby countries, ebolavirus hemorrhagic fever in West Africa, chikungunya in the Western Hemisphere, and the re-emergence of poliomyelitis.


title: Symmetrical polyneuropathy in Coronavirus Disease 2019 (COVID-19)

text: The outbreak of the novel coronavirus that began in late December 2019 was announced as a pandemic by the World Health Organization as the number of cases is increasing exponentially throughout the globe. We present a patient with confirmed SARS-CoV-2 pneumonia developing symmetric polyneuropathy. To our knowledge, extrapulmonary clinical presentations of 2019 novel coronavirus disease (COVID-19) have rarely been reported. This case highlights the possible association between SARS-CoV-2 infection and nervous system involvement.


title: Somatics of Early Buddhist Mindfulness and How to Face Anxiety

text: The body is a central object of the cultivation of mindfulness, in the way this has been described in relevant Pāli discourses and their parallels. At the background of such cultivation stands the absence of positing a mind-body duality and a lack of concern with a particular physical location of the mind in early Buddhist thought. Moreover, the various exercises that involve directing mindfulness to the body need to be considered in conjunction in order to arrive at a balanced understanding of their overarching purpose. Out of the different possible modalities of cultivating mindfulness in this way, the discourses present awareness directed to one’s own bodily postures as a practice already undertaken by the Buddha-to-be when he was still in quest of awakening. In this particular setting, such mindfulness of postures served as a way of facing fear. The potential of this exercise to provide a grounding in embodied mindfulness, being fully in the here and now, is of particular relevance to the challenges posed by the current pandemic.


title: A novel L-type lectin was required for the multiplication of WSSV in red swamp crayfish (Procambarus clakii)

text: Abstract L-type lectins are involved in glycoproteins secretory pathways and are associated with many immune responses. There is growing evidence that L-type lectins are also involved in viral replication. In this study, a novel L-type lectin (named as PcL-lectin) was identified from red swamp crayfish (Procambarus clakii). Gene sequencing and phylogenetic tree analysis results showed that the PcL-lectin was a kind of endoplasmic reticulum Golgi intermediate compartment-53 (ERGIC-53). The expression level of PcL-lectin was significantly down regulated in crayfish after challenged with white spot syndrome virus (WSSV). Recombinant PcL-lectin protein facilitated the replication of WSSV in crayfish. In addition, WSSV replication was decreased when endogenous PcL-lectin was knocked down by RNA interference in crayfish. Furthermore, PcL-lectin may interact with VP24, an envelope protein of WSSV. Our results suggest that PcL-lectin may be required for the multiplication of WSSV, and will pave a new way for the developing of strategies against WSSV infection.


title: Does high cardiorespiratory fitness confer some protection against pro‐inflammatory responses after infection by SARS‐CoV‐2?

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symtoms of SARS‐CoV‐2 and the subsequent prognosis is worsened in individuals who have pre‐exisiting comorbidities prior to infection by the virus. Individuals with obesity/overweight, insulin resistance and diabetes typically have chronic low‐grade inflammation characterized by increased levels of several pro‐inflammatory cytokines and the inflammasome: this state predisposes to greater risk for infection along with more adverse outcomes. Here we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune‐protection against Covid‐19 by attenuating the “cytokine storm syndrome” often experienced by “at risk” individuals.


title: A meta‐analysis suggesting that the relationship between biodiversity and risk of zoonotic pathogen transmission is idiosyncratic

text: Zoonotic pathogens are significant burdens on global public health. Because they are transmitted to humans from non‐human animals, the transmission dynamics of zoonoses are necessarily influenced by the ecology of their animal hosts and vectors. The ‘dilution effect’ proposes that increased species diversity reduces disease risk, suggesting that conservation and public health initiatives can work synergistically to improve human health and wildlife biodiversity. However, the meta‐analysis that we present here indicates a weak and highly heterogeneous relationship between host biodiversity and disease. Our results suggest that disease risk is more likely a local phenomenon that relies on the specific composition of reservoir hosts and vectors, and their ecology, rather than patterns of species biodiversity.


title: Etiology and characteristics of community-acquired pneumonia in an influenza epidemic period

text: Abstract Purpose The etiology of community-acquired pneumonia (CAP) in hospital patients is often ambiguous due to the limited pathogen detection. Lack of a microbiological diagnosis impairs precision treatment in CAP. Methods Specimens collected from the lower respiratory tract of 195 CAP patients, viruses were measured by the Single-plex real-time PCR assay and the conventional culture method was exploited for bacteria. Results Among the 195 patients, there were 46 (23.59%) pure bacterial infections, 20 (10.26%) yeast infections, 32 (16.41%) pure viral infections, 8 (4.10%) viral-yeast co-infections, and 17 (8.72%) viral-bacterial co-infections. The two most abundant bacteria were Acinetobacter baumannii and klebsiella pneumoniae, whereas the most common virus was influenza A. Conclusions Non-influenza respiratory microorganisms frequently co-circulated during the epidemic peaks of influenza, which easily being ignored in CAP therapy. In patients with bacterial and viral co-infections, identifying the etiologic agent is crucial for patient’s therapy.


title: The Swiss approach to the COVID‐19 outbreak

text: Angelico et al. described the impact of the novel coronavirus (COVID‐19) outbreak on organ transplantation in Italy (1), where only one center in Milan has limited transplant activity to most urgent cases. The rest of the country continued with the regular allocation policy (1). In Switzerland, which has more COVID‐19 cases per capita than Italy (2), we have opted for a stepwise approach.


title: ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes, and its applications in analyzing SARS-CoV genomes

text: Abstract A new system to recognize protein coding genes in the coronavirus genomes, specially suitable for the SARS-CoV genomes, has been proposed in this paper. Compared with some existing systems, the new program package has the merits of simplicity, high accuracy, reliability, and quickness. The system ZCURVE_CoV has been run for each of the 11 newly sequenced SARS-CoV genomes. Consequently, six genomes not annotated previously have been annotated, and some problems of previous annotations in the remaining five genomes have been pointed out and discussed. In addition to the polyprotein chain ORFs 1a and 1b and the four genes coding for the major structural proteins, spike (S), small envelop (E), membrane (M), and nuleocaspid (N), respectively, ZCURVE_CoV also predicts 5–6 putative proteins in length between 39 and 274 amino acids with unknown functions. Some single nucleotide mutations within these putative coding sequences have been detected and their biological implications are discussed. A web service is provided, by which a user can obtain the annotated result immediately by pasting the SARS-CoV genome sequences into the input window on the web site (http://tubic.tju.edu.cn/sars/). The software ZCURVE_CoV can also be downloaded freely from the web address mentioned above and run in computers under the platforms of Windows or Linux.


title: Decreased NHE3 activity and trafficking in TGEV-infected IPEC-J2 cells via the SGLT1-mediated P38 MAPK/AKt2 pathway

text: Abstract Transmissible gastroenteritis virus (TGEV) primarily replicates in intestinal epithelial cells and causes severe damage to host cells, resulting in diarrhea. Surface NHE3 serves as the key regulatory site controlling electroneutral Na+ absorption. In this study, our results showed that the surface NHE3 content was significantly reduced following TGEV infection, whereas the total level of protein expression was not significantly changed, and NHE3 activity gradually decreased with prolonged infection time. We then inhibited SGLT1 expression by lentiviral interference and drug inhibition, respectively. Inhibition studies showed that the level of phosphorylation of the downstream key proteins, MAPKAPK-2 and EZRIN, in the SGLT1-mediated p38MAPK/AKt2 signaling pathway was significantly increased. The surface NHE3 expression was also significantly increased, and NHE3 activity was also significantly enhanced. These results demonstrate that a TGEV infection can inhibit NHE3 translocation and attenuates sodium-hydrogen exchange activity via the SGLT1-mediated p38MAPK/AKt2 signaling pathway, affecting cellular electrolyte absorption leading to diarrhea.


title: Suggestions for the Care of Patients with Liver Disease During the Coronavirus 2019 Pandemic

text: This document, written by the French Association for the Study of the Liver (AFEF) board, aims to provide information to physicians involved in the care of patients with liver disease during the Coronavirus disease (COVID-19) epidemic. These are not based on a systematic review of the literature and a rigorous evaluation using the GRADE method. These are recommendations based on feedback from China available in the form of original articles or letters – for which the scientific evidence is often modest – and the rules put forward by American (1) and European (Boettler et al, 2020) hepatology societies, the French National Digestive Cancer Thesaurus (Di Fiore et al., 2020) and the Francophone Transplantation Society (4). These suggestions require adjustment according to the geographical particularities of the epidemic, available standard procedures and access to local resources. This document will be updated as regularly as possible according to the evolution of our knowledge and characteristics on the epidemic.


title: COVID-19 and emerging viral infections: The case for interferon lambda

text: With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.


title: A sensitive retroviral pseudotype assay for influenza H5N1‐neutralizing antibodies

text: Background The World Health Organisation (WHO) recommended the development of simple, safe, sensitive and specific neutralization assays for avian influenza antibodies. We have used retroviral pseudotypes bearing influenza H5 hemagglutinin (HA) as safe, surrogate viruses for influenza neutralization assays which can be carried out at Biosafety Level 2. Results Using our assay, sera from patients who had recovered from infection with influenza H5N1, and sera from animals experimentally immunized or infected with H5 tested positive for the presence of neutralizing antibodies to H5N1. Pseudotype neutralizing antibody titers were compared with titers obtained by hemagglutinin inhibition (HI) assays and microneutralization (MN) assays using live virus, and showed a high degree of correlation, sensitivity and specificity. Conclusions The pseudotype neutralization assay is as sensitive as horse erythrocyte HI and MN for the detection of antibodies to H5N1. It is safer, and can be applied in a high‐throughput format for human and animal surveillance and for the evaluation of vaccines.


title: Pathology Consultation on Influenza Diagnostics

text: Objectives: To describe the strengths and limitations of the available influenza diagnostics, with a focus on rapid antigen detection assays and nucleic acid detection assays. Methods: A case-based presentation is used to illustrate the potential limitations of rapid antigen detection assays for influenza. Results: Influenza is a seasonal illness; estimates attribute influenza to approximately 200,000 hospitalizations and 41,000 deaths in the United States annually. Antigen detection assays for influenza are rapid and convenient, and thus are widely used in a variety of health care settings, even though the sensitivity of these assays may be suboptimal. The United States Food and Drug Administration has recently created new guidelines intended to improve the oversight and performance characteristics of influenza antigen detection assays. Molecular assays, although more costly and complex, are more sensitive and may be designed to simultaneously detect multiple respiratory pathogens within a single assay. Conclusions: Diagnostic assays for influenza can vary greatly with regards to analytical performance characteristics, complexity, turnaround time and cost. This can have important patient care and infection prevention implications.


Neuropathology of COVID‐19: where are the neuropathologists?


title: Immunohistochemical studies on meningoencephalitis in feline infectious peritonitis (FIP)

text: The present study describes the association between inflammatory cell types and feline infectious peritonitis virus (FIPV) antigen in the brain of 4 cats diagnosed as feline infectious peritonitis (FIP). Immunohistochemically, FIPV antigens were detected in the inflammatory foci of the leptomeninges, choroid plexus and ventricles in 3 of the 4 cats. In 3 cases, inflammatory foci mainly consisted of CD204- and Iba1-positive macrophages, and the FIPV antigens were found in the macrophages. In the other case which was negative for FIPV antigen, severe inflammation predominantly consisting of CD20-positive B lymphocytes was observed in the leptomeninges and subventricles, accompanied with diffuse proliferation of gemistocytic astrocytes. The difference in histopathology may reflect the inflammatory process or the strain variation of FIP virus.


title: Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007

text: To determine the aetiological role and epidemiological profile of common respiratory viruses in adults with acute respiratory tract infections (ARTIs), a 2-year study was conducted in Beijing, China, from May 2005 to July 2007. Nose and throat swab samples from 5808 ARTI patients were analysed by PCR methods for common respiratory viruses, including influenza viruses (IFVs) A, B, and C, parainfluenza viruses (PIVs) 1–4, enteroviruses (EVs), human rhinoviruses (HRVs), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1, and adenoviruses (ADVs). Viral pathogens were detected in 34.6% of patient samples, and 1.6% of the patients tested positive for more than one virus. IFVs (19.3%) were the dominant agents detected, followed by HRVs (6.5%), PIVs (4.3%), EVs (3.2%), and HCoVs (1.1%). ADVs, RSV and HMPV were also detected (<1%). The viral detection rates differed significantly between infections of the lower and upper respiratory tracts in the sample population: PIVs, the second most commonly detected viral agents in lower acute respiratory tract infections (LRTIs), were more prevalent than in upper acute respiratory tract infections, indicating that the pathogenic role of PIVs in LRTIs should be investigated. Currently, this study is the largest-scale investigation of respiratory virus infections in China with multiple agent detection, providing baseline data for further studies of respiratory virus infections in adults with ARTIs.


title: Mortality threats and technology effects on tourism

text: • Investigates people's responses to tourism during Covid-19 lockdown; • Uses an experimental approach in tourism; • Investigates preference for innovative touristic virtual tours in relation to threat and self-esteem; • Combines research in psychology (Terror Management Theory) with that in tourism; • Discusses practical and research implications and future research avenues for tourism research.


title: Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells

text: The genomes of coronaviruses carry accessory genes known to be associated with viral virulence. The single accessory gene of porcine epidemic diarrhea virus (PEDV), ORF3, is dispensable for virus replication in vitro, while viral mutants carrying ORF3 truncations exhibit an attenuated phenotype of which the underlying mechanism is unknown. Here, we studied the effect of ORF3 deletion on the proliferation of PEDV in Vero cells. To this end, four recombinant porcine epidemic diarrhea viruses (PEDVs) were rescued using targeted RNA recombination, three carrying the full-length ORF3 gene from different PEDV strains, and one from which the ORF3 gene had been deleted entirely. Our results showed that PEDVs with intact or naturally truncated ORF3 replicated to significantly higher titers than PEDV without an ORF3. Further characterization revealed that the extent of apoptosis induced by PEDV infection was significantly lower with the viruses carrying an intact or C-terminally truncated ORF3 than with the virus lacking ORF3, indicating that the ORF3 protein as well as its truncated form interfered with the apoptosis process. Collectively, we conclude that PEDV ORF3 protein promotes virus proliferation by inhibiting cell apoptosis caused by virus infection. Our findings provide important insight into the role of ORF3 protein in the pathogenicity of PEDV.


title: Coronavirus disease 2019 (COVID-19): A literature review

text: Abstract In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.


title: Enfuvirtide−PEG conjugate: A potent HIV fusion inhibitor with improved pharmacokinetic properties

text: Enfuvirtide (ENF) is a clinically used peptide drug for the treatment of HIV infections, but its poor pharmacokinetic profile (T(1/2) = 1.5 h in rats) and low aqueous solubility make the therapy expensive and inconvenience. In this study, we present a simple and practical strategy to address these problems by conjugating ENF with polyethylene glycol (PEG). Site-specific attachment of a 2 kDa PEG at the N-terminus of ENF resulted in an ENF−PEG (EP) conjugate with high solubility (≥3 mg/mL) and long half-life in rats (T(1/2) = 16.1 h). This conjugate showed similar antiviral activity to ENF against various primary HIV-1 isolates (EC(50) = 6–91 nM). Mechanistic studies suggested the sources of the antiviral potency. The conjugate bound to a functional domain of the HIV gp41 protein in a helical conformation with high affinity (K(d) = 307 nM), thereby inhibiting the gp41-mediated fusion of viral and host-cell membranes. As PEG conjugation has advanced many bioactive proteins and peptides into clinical applications, the EP conjugate described here represents a potential new treatment for HIV infections that may address the unmet medical needs associated with the current ENF therapy.


Abstract 32. Borna virus encephalitis in rats: behavioral changes of aggression leading to apathy


title: Considerations for Bedside Urologic Procedures in Patients with Severe Acute Respiratory Syndrome Coronavirus-2

text: ABSTRACT Objective To provide guidance when performing bedside urologic procedures on SARS-CoV-2 positive patients and offer considerations to maximize the safety of the patients and providers, conserve supplies, and provide optimal management of urologic issues. Methods Urologic trainees and attending physicians at our institution, who are familiar with existing safety recommendations and guidelines regarding the care of infected patients, were queried regarding their experiences to determine an expert consensus on best practices for bedside procedures for SARS-CoV-2 positive patients. Results Our team developed the following general recommendations for urologic interventions on SARS-CoV-2 positive patients: maximize use of telehealth (even for inpatient consults), minimize in-room time, use personal protective equipment appropriately, enlist a colleague to assist, and acquire all supplies that may be needed and maintain them outside the room. Detailed recommendations were also developed for difficult urethral catheterization, bedside cystoscopy, incision and drainage of abscesses, and gross hematuria/clot irrigations. Conclusions As patients hospitalized with SARS-CoV-2 infection are predominantly men over 50 years old, there are significant urologic challenges common in this population that have emerged with this pandemic. While there is tremendous variation in how different regions have been affected, the demographics of SARS-CoV-2 mean that urologists will continue to have a unique role in helping to manage these patients. Here, we summarize recommendations for bedside urologic interventions specific to SARS-CoV-2 positive patients based on experiences from a large metropolitan hospital system. Regulations and requirements may differ on an institutional basis, so these guidelines are intended to augment specific local protocols.


title: Border Screening for SARS

text: With the rapid international spread of severe acute respiratory syndrome (SARS) from March through May 2003, Canada introduced various measures to screen airplane passengers at selected airports for symptoms and signs of SARS. The World Health Organization requested that all affected areas screen departing passengers for SARS symptoms. In spite of intensive screening, no SARS cases were detected. SARS has an extremely low prevalence, and the positive predictive value of screening is essentially zero. Canadian screening results raise questions about the effectiveness of available screening measures for SARS at international borders.


One Virus, Undivided … Equity, And The Corona Virus


title: Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis

text: Abstract Among the various respiratory viruses infecting human beings, coronaviruses are important pathogens, which usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, and various types of respiratory distress syndrome. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Nevertheless, for almost three decades now, data reported in the scientific literature has also demonstrated that, like it was described for other human viruses, coronaviruses have neuroinvasive capacities since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Neuroinvasive coronaviruses could damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuroimmunopathology) and/or viral replication, which directly induces damage to CNS cells (virus-induced neuropathology). Given all these properties, it has been suggested that these opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of neurologic diseases for which the etiology remains poorly understood. Herein, we present host and viral factors that participate in the regulation of the possible pathogenic processes associated with CNS infection by human coronaviruses and we try to decipher the intricate interplay between virus and host target cells in order to characterize their role in the virus life cycle as well as in the capacity of the cell to respond to viral invasion.


title: siRNAs targeting terminal sequences of the SARS-associated coronavirus membrane gene inhibit M protein expression through degradation of M mRNA

text: Abstract SARS-associated coronavirus (SCoV) M protein plays a key role in viral assembly and budding. Recent studies revealed that M protein could interact with N protein in the Golgi complex. In this study, we showed that SCoV M protein co-localized in the Golgi apparatus with a Golgi vector marker. To study M protein function, three candidate small interfering RNAs (siRNAs) corresponding to M gene sequences were designed, transcribed in vitro, and then tested for their ability to silence M protein expression. The plasmid, pEGFP-M, encoding SCoV M protein as a fusion protein with EGFP, was used for silencing and for reporter gene detection in HEK 293T cells transfected with siRNA constructs. The results showed that the mean green fluorescence intensity and M RNA transcripts were significantly reduced, and that the expression of M glycoprotein was strongly inhibited in those cells co-transfected with M-specific siRNAs. These findings demonstrated that the three M-specific siRNAs were able to specifically and effectively inhibit M glycoprotein expression in cultured cells by blocking the accumulation of mRNA, which provides an approach for studies on the functions of M protein and for the development of novel prophylactic or therapeutic agents for SCoV infection.


title: Molecular surveillance of traditional and emerging pathogens associated with canine infectious respiratory disease

text: Abstract A molecular survey for traditional and emerging pathogens associated with canine infectious respiratory disease (CIRD) was conducted in Italy between 2011 and 2013 on a total of 138 dogs, including 78 early acute clinically ill CIRD animals, 22 non-clinical but exposed to clinically ill CIRD dogs and 38 CIRD convalescent dogs. The results showed that canine parainfluenza virus (CPIV) was the most commonly detected CIRD pathogen, followed by canine respiratory coronavirus (CRCoV), Bordetella bronchiseptica, Mycoplasma cynos, Mycoplasma canis and canine pneumovirus (CnPnV). Some classical CIRD agents, such as canine adenoviruses, canine distemper virus and canid herpesvirus 1, were not detected at all, as were not other emerging respiratory viruses (canine influenza virus, canine hepacivirus) and bacteria (Streptococcus equi subsp. zooepidemicus). Most severe forms of respiratory disease were observed in the presence of CPIV, CRCoV and M. cynos alone or in combination with other pathogens, whereas single CnPnV or M. canis infections were detected in dogs with no or very mild respiratory signs. Interestingly, only the association of M. cynos (alone or in combination with either CRCoV or M. canis) with severe clinical forms was statistically significant. The study, while confirming CPIV as the main responsible for CIRD occurrence, highlights the increasing role of recently discovered viruses, such as CRCoV and CnPnV, for which effective vaccines are not available in the market.


title: The ADAM metalloproteinases

text: Abstract The ADAMs (a disintegrin and metalloproteinase) are a fascinating family of transmembrane and secreted proteins with important roles in regulating cell phenotype via their effects on cell adhesion, migration, proteolysis and signalling. Though all ADAMs contain metalloproteinase domains, in humans only 13 of the 21 genes in the family encode functional proteases, indicating that at least for the other eight members, protein–protein interactions are critical aspects of their biological functions. The functional ADAM metalloproteinases are involved in “ectodomain shedding” of diverse growth factors, cytokines, receptors and adhesion molecules. The archetypal activity is shown by ADAM-17 (tumour necrosis factor-α convertase, TACE), which is the principal protease involved in the activation of pro-TNF-α, but whose sheddase functions cover a broad range of cell surface molecules. In particular, ADAM-17 is required for generation of the active forms of Epidermal Growth Factor Receptor (EGFR) ligands, and its function is essential for the development of epithelial tissues. Several other ADAMs have important sheddase functions in particular tissue contexts. Another major family member, ADAM-10, is a principal player in signalling via the Notch and Eph/ephrin pathways. For a growing number of substrates, foremost among them being Notch, cleavage by ADAM sheddases is essential for their subsequent “regulated intramembrane proteolysis” (RIP), which generates cleaved intracellular domains that translocate to the nucleus and regulate gene transcription. Several ADAMs play roles in spermatogenesis and sperm function, potentially by effecting maturation of sperm and their adhesion and migration in the uterus. Other non-catalytic ADAMs function in the CNS via effects on guidance mechanisms. The ADAM family are thus fundamental to many control processes in development and homeostasis, and unsurprisingly they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. This review will provide an overview of current knowledge of the human ADAMs, discussing their structure, function, regulation and disease involvement.


title: Improving care for older adults in the Emergency Department warrants greater investment in geriatric nursing—Stat!

text: Older adults use the Emergency Department (ED) more than any other age group besides infants. Despite high utilization, both the physical environment and care processes in the traditional ED are poorly suited to address the complex needs of older adults. As a result, older adults often experience poor outcomes in the ED. Geriatric nursing has been at the forefront of efforts to develop Geriatric Emergency Department Interventions (GEDI's) to try to address these deficits and improve care. As frontline providers with frequent patient contact, nursing brings critical viewpoints to these issues. This article provides some resources and other ideas for how frontline nurses can improve care for older adults in the ED. Ultimately, to have meaningful impacts on care of older adults in the ED, there is a dire need for greater financial investment specific to geriatric nursing education, training, and research in the ED.


title: Epidemiology and Potential Preventative Measures for Viral Infections in Children With Malignancy and Those Undergoing Hematopoietic Cell Transplantation

text: In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections.


title: Efficacy of genogroup 1 based porcine epidemic diarrhea live vaccine against genogroup 2 field strain in Japan

text: BACKGROUND: Porcine epidemic diarrhea (PED) is a lethal infectious disease in suckling piglets with symptoms including watery diarrhea caused by PED virus (PEDV). Since the late 1990’s, live vaccines based on genogroup 1 virus have been used in Japan, and a significant amount of the vaccine has been used even after new genogroups invaded in 2013. In this study, we evaluated the effect of a conventional PED live vaccine on a newly prevalent genogroup 2 field strain in experimental and field situations. METHODS: Two pregnant sows were administered twice the live vaccine before farrowing. A pregnant sow was served as a negative control. All newborn piglets were challenged with the genogroup 2 virus, and clinical signs were monitored for 7 days post challenge. PEDV-specific immune responses in serum and milk of the sows were assayed by virus neutralization assay. The efficacy of PED live vaccine in vaccinated or non-vaccinated farms was evaluated by comparing the mortality rate of suckling piglets after the onset of PED. RESULTS: The challenged piglets exhibited watery diarrhea with or without vaccination. However, the clinical score of piglets born from vaccinated sows significantly improved after the 4th day of the challenge. The survival rate of piglets in the vaccinated group at the end of the experimental period was 80%, whereas in the control group was 0%. Neutralizing antibody titers in serum and milk of control sow was negative throughout the experimental period, whereas high titers were observed in the vaccinated sows. The vaccinated farms significantly reduced the mortality rate of suckling piglets after the onset of PED, compared to farms not vaccinated. CONCLUSIONS: The conventional PED live vaccine induced the lactogenic immunity to vaccinated sows and showed partial protection against the genogroup 2 virus both under the experimental and field conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0940-8) contains supplementary material, which is available to authorized users.


Re: Silke Gillessen Sommer, Thomas Powles. Advice for Medical Oncology Care of Urological Cancer Patients During the COVID-19 Pandemic. Eur Urol. In press Is It Always Correct to Continue Androgen Receptor Signaling Inhibitors in the COVID-19 Era?


title: This Time Must Be Different: Disparities During the COVID-19 Pandemic

text: African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.


title: Considerations for a WHO European strategy on health-care-associated infection, surveillance, and control

text: Summary Health-care-associated infection (HAI) is a major issue of patient safety with a substantial impact on morbidity, mortality, and use of additional resources worldwide. In April 2004, the WHO Regional Office for Europe organised the first international consultation to address the issue of HAI in eastern and central Europe. The main objectives of the consultation were to identify the primary needs and obstacles for the prevention and control of HAI at country level, to design the essential components of an international strategy to effectively address the issue of HAI, and to identify specific priorities and recommendations for interventions by the WHO and other international institutions. An update on HAI activities and related networks throughout Europe, together with the outcome of the meeting, are presented, with special emphasis on future considerations for a European WHO strategy on HAI prevention.


title: Otolaryngology in the COVID-19 pandemic era: the impact on our clinical practice

text: PURPOSE: To give an overview of the current knowledge about COVID-19 pandemic and its impact on otolaryngology clinical practice. METHODS: Recent findings about SARS-CoV-2 virus and the COVID-19 infection it causes are reviewed. In addition to international databases and in the absence of hard scientific data, literature search included reports published online from scientific societies and other institutions. RESULTS: The role of anosmia as a COVID-19-related symptom is presented. Further, considerations about steroid administration in ENT-related conditions are also discussed. Due to the close work with mucosa surfaces of the upper aerodigestive tract, otolaryngologists and surrounding staff are considered high risk for coronavirus transmission. Hence, staff protection measures for ENT examinations, surgeries and other procedures during COVID-19 pandemic are recommended. CONCLUSION: Knowledge and evidence about the impact of COVID-19 infection on otolaryngology clinical practice are accumulating rapidly. Additionally to patient’s management, safety of health care professionals should be a main goal right now by following strict safety guidelines.


title: 5 Molecular Microbiology

text: Abstract Background Nucleic acid (NA) amplification techniques are now commonly used to diagnose and manage patients with infectious diseases. The growth in the number of Food and Drug Administration–approved test kits and analyte-specific reagents has facilitated the use of this technology in clinical laboratories. Technological advances in NA amplification techniques, automation, NA sequencing, and multiplex analysis have reinvigorated the field and created new opportunities for growth. Simple, sample-in, answer-out molecular test systems are now widely available that can be deployed in a variety of laboratory and clinical settings. Molecular microbiology remains the leading area in molecular pathology in terms of both the numbers of tests performed and clinical relevance. NA-based tests have reduced the dependency of the clinical microbiology laboratory on more traditional antigen detection and culture methods and created new opportunities for the laboratory to impact patient care. Content This chapter reviews NA testing as it applies to specific pathogens or infectious disease syndromes, with a focus on those diseases for which NA testing is now considered the standard of care and highlights the unique challenges and opportunities that these tests present for clinical laboratories.


title: Bayes' theorem, COVID19, and screening tests

text: The COVID19 crisis has provided a portal to revisit and understand qualities of screening tests and the importance of Bayes' theorem in understanding how to interpret results and implications of next actions.


title: Neurology and the clinical anatomist

text: Clinical examination allows the neurologist to test hypotheses generated by their interpretation of the patient's story. By eliciting abnormal clinical signs, the examining doctor works out a differential diagnosis for the part of the nervous system affected and, using information from the clinical history, a differential diagnosis of the pathology. Clinical examination also allows the clinician to observe and quantify function, hear more story and provide reassurance. The focus of the examination should be dictated by the hypothesis being tested, the patient's clinical state and the situation. Examination of the different parts of the nervous system remains very important in all clinical situations as the best available index of function of the nervous system as a whole.


Head and neck surgery is a high-risk procedure for COVID-19 transmission and there is a need for a preventive strategy to protect professionals


title: Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti-breast cancer agents

text: Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high-throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H-TOPOI) in a yeast-based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H-TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H-TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H-TOPOI. The findings of the current study indicated that SMD1168H-TOPOI has similar characteristics to MDA-MB-231 cells; therefore, it can be used in a yeast-based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.


title: A pilot study of bioaerosol reduction using an air cleaning system during dental procedures

text: Background Bioaerosols are defined as airborne particles of liquid or volatile compounds that contain living organisms or have been released from living organisms. The creation of bioaerosols is a recognized consequence of certain types of dental treatment and represents a potential mechanism for the spread of infection. Objectives The aims of the present study were to assess the bioaerosols generated by certain dental procedures and to evaluate the efficiency of a commercially available Air Cleaning System (ACS) designed to reduce bioaerosol levels. Methods Bioaerosol sampling was undertaken in the absence of clinical activity (baseline) and also during treatment procedures (cavity preparation using an air rotor, history and oral examination, ultrasonic scaling and tooth extraction under local anaesthesia). For each treatment, bioaerosols were measured for two patient episodes (with and without ACS operation) and between five and nine bioaerosol samples were collected. For baseline measurements, 15 bioaerosol samples were obtained. For bioaerosol sampling, environmental air was drawn on to blood agar plates using a bioaerosol sampling pump placed in a standard position 20 cm from the dental chair. Plates were incubated aerobically at 37°C for 48 hours and resulting growth quantified as colony forming units (cfu/m(3)). Distinct colony types were identified using standard methods. Results were analysed statistically using SPSS 12 and Wilcoxon signed rank tests. Results The ACS resulted in a significant reduction (p = 0.001) in the mean bioaerosols (cfu/m(3)) of all three clinics compared with baseline measurements. The mean level of bioaerosols recorded during the procedures, with or without the ACS activated respectively, was 23.9 cfu/m(3) and 105.1 cfu/m(3) (p = 0.02) for cavity preparation, 23.9 cfu/m(3) and 62.2 cfu/m(3) (p = 0.04) for history and oral examination; 41.9 cfu/m(3) and 70.9 cfu/m(3) (p = 0.01) for ultrasonic scaling and 9.1 cfu/m(3) and 66.1 cfu/m(3) (p = 0.01) for extraction. The predominant microorganisms isolated were Staphylococcus species and Micrococcus species. Conclusion These findings indicate potentially hazardous bioaerosols created during dental procedures can be significantly reduced using an air cleaning system.


title: Meeting report: Global vaccine and immunization research forum, 2018

text: Abstract Every two years, the Global Vaccine and Immunization Research Forum takes stock of global research in vaccines and immunization. As in prior years, the 2018 meeting addressed vaccine discovery, development, decision-making, and deployment. This time, however, it also featured two overarching themes: “Innovating for Equity” and “End-to-End Integration.” Significant advances have been made in the last two years, but participants noted that some important goals of the Global Vaccine Action Plan are not being met and called urgently for innovation in improving access to vaccines. Two factors were highlighted as crucial to improving coverage: a focus on equity and sustainability throughout the immunization ecosystem, and an enabling political environment that prioritizes health and immunization.


title: Computational characterization and design of SARS coronavirus receptor recognition and antibody neutralization

text: Abstract The sequential determination of crystal structures of the SARS coronavirus spike receptor-binding domain (RBD) in complex with its cellular receptor or neutralizing antibody opened a door for the design and development of antiviral competitive inhibitors. Based on those complex structures, we conduct computational characterization and design of RBD-mediated receptor recognition and antibody neutralization. The comparisons between computational predictions and experimental evidences validate our structural bioinformatics protocols. And the calculations predict a number of single substitutions on RBD, receptor or antibody that could remarkably elevate the binding affinities of those complexes. It is reasonable to anticipate our structure-based computation-derived hypotheses could be informative to the future biochemical and immunological tests.


title: Preparing for the Unthinkable: Emergency Preparedness for the Hematopoietic Cell Transplant Program

text: Abstract Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.


title: Modelling management strategies for a disease including undetected sub-clinical infection: Bacterial kidney disease in Scottish salmon and trout farms

text: Disease is a major constraint on animal production and welfare in agriculture and aquaculture. Movement of animals between farms is one of the most significant routes of disease transmission and is particularly hard to control for pathogens with subclinical infection. Renibacterium salmoninarum causes bacterial kidney disease (BKD) in salmonid fish, but infection is often sub-clinical and may go undetected with major potential implications for disease control programmes. A Susceptible-Infected model of R. salmoninarum in Scottish aquaculture has been developed that subdivides the infected phase between known and undetected sub-clinically infected farms and diseased farms whose status is assumed to be known. Farms officially known to be infected are subject to movement controls restricting spread of infection. Model results are sensitive to prevalence of undetected infection, which is unknown. However, the modelling suggests that controls that reduce BKD prevalence include improve biosecurity on farms, including those not known to be infected, and improved detection of infection. Culling appears of little value for BKD control. BKD prevalence for rainbow trout farms is less sensitive to controls than it is for Atlantic salmon farms and so different management strategies may be required for the sectors.


title: One-Year Visiting Care Service Treatment with Korean Medicine for a Solitary Elderly Woman in a Public Health Setting: A Case Report

text: Abstracts In public health, the plight of the solitary elderly is associated with serious social and medical burden. In this vulnerable population, neuropsychiatric complications such as senile depression and dementia as well as chronic pain conditions often co-occur. In this case report, we present a case of an 81-year-old solitary woman who received one year of visiting care service with Korean medicine treatments in a public health setting. During the one year, her pain severity (measured using numeric rating scale) remained moderate after her initial decline and her depressive symptoms and cognitive function scales (Geriatric Depression Scale-Short Form Korean and the Korean version of the Mini-Mental State Examination for Dementia Screening) remained almost unchanged; however, another cognitive function scale (Korean version of the Montreal Cognitive Assessment) showed noticeable improvements. This case report suggests that providing visiting care services with Korean medicine may be a viable strategy for addressing the issues of the solitary elderly.


title: WU and KI polyomavirus infections in pediatric hematology/oncology patients with acute respiratory tract illness

text: Abstract Background WU and KI polyomaviruses (PyV) were discovered in 2007 in respiratory tract samples in adults and children. Other polyomaviruses (BKPyV and JCPyV) have been associated with illness in immunocompromised patients, and some studies suggest a higher prevalence of WUPyV and KIPyV in this population. Objective To determine whether a higher prevalence or viral load for WUPyV and KIPyV exists in immunocompromised children compared with immunocompetent children. Study design We measured the prevalence and viral load of WU and KI PyV by quantitative real-time PCR of viral DNA in respiratory tract specimens from pediatric hematology/oncology patients and immunocompetent controls with acute respiratory illnesses. Results The prevalence of WUPyV in the immunocompromised population was 5/161 (3%) versus 14/295 (5%) in the control population (P =0.5), and 9/161 (5.6%) versus 7/295 (2.3%) respectively for KIPyV (P =0.13). The mean viral load (in copies per cell or mL of sample) for KIPyV, was higher in the immunocompromised group compared to the control group (P =0.019), but was not statistically different for WUPyV. A higher prevalence was seen in the hematopoietic stem cell transplant recipients compared with other immunocompromised patients (6/26 versus 3/43, P =0.054). Viral persistence was demonstrated only in 1/25 (4%) of sequential samples for KIPyV, and no persistence was seen for WUPyV. Conclusions A higher prevalence of WUPyV or KIPyV in the immunocompromised population compared with the immunocompetent group was not demonstrated. Higher viral loads for KIPyV in the immunocompromised group may suggest an increased pathogenic potential in this population.


title: Pathobiology of secondary immune thrombocytopenia

text: Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.


title: Evolution of the Chinese guarantee network under financial crisis and stimulus program

text: Our knowledge about the evolution of guarantee network in downturn period is limited due to the lack of comprehensive data of the whole credit system. Here we analyze the dynamic Chinese guarantee network constructed from a comprehensive bank loan dataset that accounts for nearly 80% total loans in China, during 01/2007-03/2012. The results show that, first, during the 2007-2008 global financial crisis, the guarantee network became smaller, less connected and more stable because of many bankruptcies; second, the stimulus program encouraged mutual guarantee behaviors, resulting in highly reciprocal and fragile network structure; third, the following monetary policy adjustment enhanced the resilience of the guarantee network by reducing mutual guarantees. Interestingly, our work reveals that the financial crisis made the network more resilient, and conversely, the government bailout degenerated network resilience. These counterintuitive findings can provide new insight into the resilience of real-world credit system under external shocks or rescues.


title: An arginine-to-proline mutation in a domain with undefined functions within the helicase protein (Nsp13) is lethal to the coronavirus infectious bronchitis virus in cultured cells

text: Abstract Genetic manipulation of the RNA genomes by reverse genetics is a powerful tool to study the molecular biology and pathogenesis of RNA viruses. During construction of an infectious clone from a Vero cell-adapted coronavirus infectious bronchitis virus (IBV), we found that a G–C point mutation at nucleotide position 15526, causing Arg-to-Pro mutation at amino acid position 132 of the helicase protein, is lethal to the infectivity of IBV on Vero cells. When the in vitro-synthesized full-length transcripts containing this mutation were introduced into Vero cells, no infectious virus was rescued. Upon correction of the mutation, infectious virus was recovered. Further characterization of the in vitro-synthesized full-length transcripts containing the G15526C mutation demonstrated that this mutation may block the transcription of subgenomic RNAs. Substitution mutation of the Arg132 residue to a positively charged amino acid Lys affected neither the infectivity of the in vitro-synthesized transcripts nor the growth properties of the rescued virus. However, mutation of the Arg132 residue to Leu, a conserved residue in other coronaviruses at the same position, reduced the recovery rate of the in vitro-synthesized transcripts. The recovered mutant virus showed much smaller-sized plaques. On the contrary, a G–C and a G–A point mutations at nucleotide positions 4330 and 9230, respectively, causing Glu–Gln and Gly–Glu mutations in or near the catalytic centers of the papain-like (Nsp3) and 3C-like (Nsp5) proteinases, did not show detectable detrimental effect on the rescue of infectious viruses and the infectivity of the rescued viruses.


title: TREM2 in Neurodegenerative Diseases

text: TREM2 variants have been identified as risk factors for Alzheimer’s disease (AD) and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor exclusively expressed on immune cells, identification of these variants conclusively demonstrates that the immune response can play an active role in the pathogenesis of NDDs. These TREM2 variants also confer the highest risk for developing Alzheimer’s disease of any risk factor identified in nearly two decades, suggesting that understanding more about TREM2 function could provide key insights into NDD pathology and provide avenues for novel immune-related NDD biomarkers and therapeutics. The expression, signaling and function of TREM2 in NDDs have been extensively investigated in an effort to understand the role of immune function in disease pathogenesis and progression. We provide a comprehensive review of our current understanding of TREM2 biology, including new insights into the regulation of TREM2 expression, and TREM2 signaling and function across NDDs. While many open questions remain, the current body of literature provides clarity on several issues. While it is still often cited that TREM2 expression is decreased by pro-inflammatory stimuli, it is now clear that this is true in vitro, but inflammatory stimuli in vivo almost universally increase TREM2 expression. Likewise, while TREM2 function is classically described as promoting an anti-inflammatory phenotype, more than half of published studies demonstrate a pro-inflammatory role for TREM2, suggesting that its role in inflammation is much more complex. Finally, these components of TREM2 biology are applied to a discussion of how TREM2 impacts NDD pathologies and the latest assessment of how these findings might be applied to immune-directed clinical biomarkers and therapeutics.


title: Comparison of outpatient medically attended and community‐level influenza‐like illness—New York City, 2013‐2015

text: BACKGROUND: Surveillance of influenza‐like illness (ILI) in the United States is primarily conducted through medical settings despite a significant burden of non‐medically attended ILI. OBJECTIVES: To assess consistency between surveillance for respiratory viruses in outpatient and community settings using ILI surveillance from the Centers for Disease Control and Prevention Influenza Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute Respiratory Infections (ARI) and Influenza‐Like Illness in the Community (MoSAIC) Study. METHODS: The Influenza Incidence Surveillance Project conducts ILI surveillance in 3 primary care clinics in New York City, and MoSAIC conducts community‐based ILI/ARI surveillance through text messaging among a cohort of New York City residents. Both systems obtain respiratory specimens from participants with ILI/ARI and test for multiple pathogens. We conducted a retrospective review of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive analyses of clinical and laboratory data. RESULTS: Five‐hundred twelve MoSAIC and 669 IISP participants met an ILI criteria (fever with cough or sore throat) and were included. Forty percent of MoSAIC participants sought care; the majority primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The relative distribution of influenza and other respiratory viruses detected was similar; however, there were statistically significant differences in the frequency that were not explained by care seeking. CONCLUSIONS: Outpatient and community‐based surveillance in the one found similar timing and relative distribution of respiratory viruses, but community surveillance in a single neighborhood may not fully capture the variations in ILI etiology that occur more broadly.


title: An ELISA for the detection of serum antibodies to both transmissible gastroenteritis virus and porcine respiratory coronavirus

text: Abstract A competition ELISA utilizing a mAb directed towards a peplomer protein epitope common to TGEV, PRCV and related feline and canine coronaviruses is described.


title: Progress towards a higher taxonomy of viruses

text: Summary The current consensus view is that a higher hierarchical taxonomy of viruses cannot be established for two reasons. Firstly, viruses appear to be polyphyletic in origin, with several sets of viruses arising by different, independent routes at different times. Secondly, subsequent virus adaptation for survival in different host/vector combinations has involved the selective acquisition of additional genes by a process of cassette or modular evolution, with these additional gene modules coming from other viruses or host genetic material. Thus, depending on the gene product used for comparison, different phylogenetic relationships can be deduced. Further virus adaptation can arise by reassortment of segmented genomes, gene duplication, deletions, frameshift mutations, point mutations or de novo development of new gene products from existing, unused reading frames. The solution to the first objection is to place all viruses in a separate kingdom and assign the current viruses to several phyla that reflect these diverse origins. The solution to the second objection is to consider the core module of replication machinery as the major criterion on which to make the initial assignments to classes and orders. For RNA viruses, the major criterion is the sequence identity of the RNA-dependent RNA polymerase. Using this criterion, the positive strand RNA viruses can be assigned to five classes that correspond to the recently recognized supergroups of RNA viruses. These five classes contain four, three, three, three and one order(s) respectively. These fourteen orders contain 31 virus families (including 17 families of plant viruses) and 48 genera (including 30 genera of plant viruses). This approach confirms the separation of the alphaviruses and flaviviruses into two families, the Togaviridae and Flaviridae, but suggests that several other current taxonomic assignments, such as the pestiviruses, hepatitis C virus, rubiviruses, hepatitis E virus and arteriviruses, may be wrong. The coronaviruses and toroviruses appear to be distinct families in distinct orders, not distinct genera of the same family as currently classified. In addition, the luteoviruses are split into two families and apple chlorotic leaf spot virus appears not to be a closterovirus but a new genus of the Potexviridae. From an analysis of the polymerase dendrograms of the dsRNA viruses, it appears that they are not closely related to each other, but belong to four additional classes (Partitiviridae, Reoviridae, Birnaviridae and Cystoviridae) and one additional order (Totiviridae) of one of the classes of positive ssRNA viruses in the same subphylum as the positive strand RNA viruses. The negative strand virus polymerase relationships confirm the assignment of the negative strand viruses to two orders in a single class in a separate subphylum of the RNA viruses. This review includes preliminary data suggesting that the DNA viruses can also be assigned to higher taxa on the basis of the sequence identities of their highly conserved DNA polymerases. The suggested use of viral polymerases to establish higher order relationships is similar in principle to the use of highly conserved ribosomal RNA gene sequences in prokaryotic and eukaryotic taxonomy. This review also discusses the assignment of 33 of the 35 groups of plant viruses into genera of 25 families based on the nature of the genome and its arrangement, the level of sequence identity and, to a lesser extent, particle morphology.


Mitteilungen der DGN


The possible impact of COVID 19 on fertility and ART


title: A case for a CUG-initiated coding sequence overlapping torovirus ORF1a and encoding a novel 30 kDa product

text: The genus Torovirus (order Nidovirales) includes a number of species that infect livestock. These viruses have a linear positive-sense ssRNA genome of ~25-30 kb, encoding a large polyprotein that is expressed from the genomic RNA, and several additional proteins expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the polyprotein coding sequence, ORF1a, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF1a. We propose that the new ORF utilizes a non-AUG initiation codon - namely a conserved CUG codon in a strong Kozak context - upstream of the ORF1a AUG initiation codon, resulting in a novel 258 amino acid protein, dubbed '30K'.


title: A recombinant DNA and vaccinia virus prime–boost regimen induces potent long-term T-cell responses to HCV in BALB/c mice

text: Abstract To explore the best prime–boost regimen and evaluate the T-cellular response memory against HCV, we constructed two DNA vaccine candidates (pVRC-CE1E2 and pAAV-CE1E2) and two recombinant viruses (rTTV-E1E2 and rAAV-E1E2) and then assessed the immune response to different prime–boost patterns in BALB/c mice. The rTTV-E1E2 boosted the immune response to HCV DNA vaccine prime significantly, and the inverted terminal repeat sequence harboring DNA construct PAAV-CE1E2 was the best prime agent in this study. Our study provides new information for both the prime–boost regimen and long-term T-cell response for HCV vaccine development.


title: Major emerging and re-emerging zoonoses in China: a matter of global health and socioeconomic development for 1.3 billion

text: Summary Emerging and re-emerging zoonoses are a significant public health concern and cause considerable socioeconomic problems globally. The emergence of severe acute respiratory syndrome (SARS), highly pathogenic avian influenza (HPAI) H5N1, avian influenza H7N9, and severe fever with thrombocytopenia syndrome (SFTS), and the re-emergence of rabies, brucellosis, and other zoonoses have had a significant effect on the national economy and public health in China, and have affected other countries. Contributing factors that continue to affect emerging and re-emerging zoonoses in China include social and environmental factors and microbial evolution, such as population growth, urbanization, deforestation, livestock production, food safety, climate change, and pathogen mutation. The Chinese government has devised new strategies and has taken measures to deal with the challenges of these diseases, including the issuing of laws and regulations, establishment of disease reporting systems, implementation of special projects for major infectious diseases, interdisciplinary and international cooperation, exotic disease surveillance, and health education. These strategies and measures can serve as models for the surveillance and response to continuing threats from emerging and re-emerging zoonoses in other countries.


title: Defective interfering particles of mouse hepatitis virus

text: Abstract After six to eight serial undiluted passages of mouse hepatitis virus (JHM strain) in DBT cell culture, a decrease in the yield of infectious virus occurred, and with further passages fluctuating yields of infectious virus were observed. The serially passaged virus interfered with the multiplication of the standard JHM virus, but not with vesicular stomatitis virus. After sucrose equilibrium centrifugation of high passage virus, a single peak contained both infectious virus and interfering activity. This virus population resembled the original JHM virus in its structural proteins, but it contained an increased proportion of a protein with a molecular weight of 65 × 103. Genomic RNA from standard JHM virus contained a single species of RNA with a molecular weight of 5.4 × 106. After five undiluted passages, however, the virion population contained two RNA species with molecular weights of 5.4 × 106 and 5.2 × 106. RNase T1 resistant oligonucleotide finger-printing of these RNAs showed that the lower molecular weight RNA had lost several oligonucleotide spots that were present in the genomic RNA of the standard JHM virus. After several serial diluted passages of passage 10 virus, a single virus population was obtained which again had only standard virus RNA with a molecular weight of 5.4 × 106 and lacked interfering activity. These results indicated that defective interfering particles were generated by serial undiluted passages of JHM virus.


docid: xwwvzikk

title: Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner

text: Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis. To verify the roles of distinct endocytic pathways, systematic approaches were used, including pharmacological inhibition, RNA interference, confocal microscopy analysis, use of fluorescently labeled virus particles, and overexpression of a dominant negative (DN) mutant. Quantification of infected cells showed that PHEV enters cells by clathrin-mediated endocytosis (CME) and that low pH, dynamin, cholesterol, and Eps15 are indispensably involved in this process. Intriguingly, PHEV invasion leads to rapid actin rearrangement, suggesting that the intactness and dynamics of the actin cytoskeleton are positively correlated with viral endocytosis. We next investigated the trafficking of internalized PHEV and found that Rab5- and Rab7-dependent pathways are required for the initiation of a productive infection. Furthermore, a GTPase activation assay suggested that endogenous Rab5 is activated by PHEV and is crucial for viral progression. Our findings demonstrate that PHEV hijacks the CME and endosomal system of the host to enter and traffic within neural cells, providing new insights into PHEV pathogenesis and guidance for antiviral drug design. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV), a nonsegmented, positive-sense, single-stranded RNA coronavirus, invades the central nervous system (CNS) and causes neurological dysfunction. Neural cells are its targets for viral progression. However, the detailed mechanism underlying PHEV entry and trafficking remains unknown. PHEV is the etiological agent of porcine hemagglutinating encephalomyelitis, which is an acute and highly contagious disease that causes numerous deaths in suckling piglets and enormous economic losses in China. Understanding the viral entry pathway will not only advance our knowledge of PHEV infection and pathogenesis but also open new approaches to the development of novel therapeutic strategies. Therefore, we employed systematic approaches to dissect the internalization and intracellular trafficking mechanism of PHEV in Neuro-2a cells. This is the first report to describe the process of PHEV entry into nerve cells via clathrin-mediated endocytosis in a dynamin-, cholesterol-, and pH-dependent manner that requires Rab5 and Rab7.


title: Sumoylation of the nucleocapsid protein of severe acute respiratory syndrome coronavirus

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a highly basic nucleocapsid (N) protein of 422 amino acids. Similar to other coronavirus N proteins, SARS-CoV N protein is predicted to be phosphorylated and may contain nuclear localization signals, serine/arginine-rich motif, RNA binding domain and regions responsible for self-association and homo-oligomerization. In this study, we demonstrate that the protein is posttranslationally modified by covalent attachment to the small ubiquitin-like modifier. The major sumoylation site was mapped to the (62)lysine residue of the N protein. Further expression and characterization of wild type N protein and K62A mutant reveal that sumoylation of the N protein drastically promotes its homo-oligomerization, and plays certain roles in the N protein-mediated interference of host cell division. This is the first report showing that a coronavirus N protein undergoes posttranslational modification by sumoylation, and the functional implication of this modification in the formation of coronavirus ribouncleoprotein complex, virion assembly and virus–host interactions.


Actualización de la situación epidemiológica de la infección por SARS-CoV-2 en España. Comentarios a las recomendaciones de manejo de la infección en pediatría


title: Bibliometric analysis of peer-reviewed literature on climate change and human health with an emphasis on infectious diseases

text: BACKGROUND: Assessing research activity is important for planning future protective and adaptive policies. The objective of the current study was to assess research activity on climate change and health with an emphasis on infectious diseases. METHOD: A bibliometric method was applied using SciVerse Scopus. Documents on climate change and human health were called “health-related literature” while documents on climate change and infectious diseases were called “infection-related literature”. The study period was from 1980 to 2019. RESULTS: The search query found 4247 documents in the health-related literature and 1207 in the infection-related literature. The growth of publications showed a steep increase after 2007. There were four research themes in the health-related literature: (1) climate change and infectious diseases; (2) climate change, public health and food security; (3) heat waves, mortality, and non-communicable diseases; and (4) climate change, air pollution, allergy, and respiratory health. The most frequently encountered pathogens/infectious diseases in the infection-related literature were malaria and dengue. Documents in infection-related literature had a higher h-index than documents in the health-related literature. The top-cited documents in the health-related literature focused on food security, public health, and infectious diseases while those in infection-related literature focused on water-, vector-, and mosquito-borne diseases. The European region had the highest contribution in health-related literature (n = 1626; 38.3%) and infection-related literature (n = 497; 41.2%). The USA led with 1235 (29.1%) documents in health-related literature and 365 (30.2%) documents in infection-related literature. The Australian National University ranked first in the health-related literature while the London School of Hygiene & Tropical Medicine ranked first in the infection-related literature. International research collaboration was inadequate. Documents published in the Environmental Health Perspectives journal received the highest citations per document. A total of 1416 (33.3%) documents in the health-related literature were funded while 419 (34.7%) documents in the infection-related literature were funded. CONCLUSION: Research on climate change and human health is on the rise with research on infection-related issues making a good share. International research collaboration should be funded and supported. Future research needs to focus on the impact of climate change on psychosocial, mental, innovations, policies, and preparedness of health systems.


title: Infectious encephalitis: Management without etiological diagnosis 48hours after onset

text: Abstract Introduction The etiological diagnosis of infectious encephalitis is often not established 48hours after onset. We aimed to review existing literature data before providing management guidelines. Method We performed a literature search on PubMed using filters such as “since 01/01/2000”, “human”, “adults”, “English or French”, and “clinical trial/review/guidelines”. We also used the Mesh search terms “encephalitis/therapy” and “encephalitis/diagnosis”. Results With Mesh search terms “encephalitis/therapy” and “encephalitis/diagnosis”, we retrieved 223 and 258 articles, respectively. With search terms “encephalitis and corticosteroid”, we identified 38 articles, and with “encephalitis and doxycycline” without the above-mentioned filters we identified 85 articles. A total of 210 articles were included in the analysis. Discussion Etiological investigations must focus on recent travels, animal exposures, age, immunodeficiency, neurological damage characteristics, and potential extra-neurological signs. The interest of a diagnosis of encephalitis for which there is no specific treatment is also to discontinue any empirical treatments initially prescribed. Physicians must consider and search for autoimmune encephalitis.


Coping with the COVID-19 crisis: A call for youth engagement and the inclusion of young people in matters that affect their lives.


title: Rhinosinusitis: Establishing definitions for clinical research and patient care

text: Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Study design Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusions The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.


title: Optimized synthesis of aminooxy-peptides as glycoprobe precursors for surface-based sugar–protein interaction studies

text: Abstract An improved procedure for solid phase coupling of Boc-aminooxyacetic acid to peptides is described. By avoiding base-containing activation mixtures which cause over-acylation, it practically suppresses this unwanted side reaction and leads to near quantitative yields of Aoa-peptides, useful as glycoprobe precursors in glycomic studies.


title: Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity

text: A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC(50) > 3x EC(50)) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC(50) < 10 μM and a CC(50) > 100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.


title: Insights into SARS-CoV transcription and replication from the structure of the nsp7–nsp8 hexadecamer

text: Coronavirus replication and transcription machinery involves multiple virus-encoded nonstructural proteins (nsp). We report the crystal structure of the hexadecameric nsp7–nsp8 supercomplex from the severe acute respiratory syndrome coronavirus at 2.4-Å resolution. nsp8 has a novel 'golf-club' fold with two conformations. The supercomplex is a unique hollow, cylinder-like structure assembled from eight copies of nsp8 and held tightly together by eight copies of nsp7. With an internal diameter of ∼30 Å, the central channel has dimensions and positive electrostatic properties favorable for nucleic acid binding, implying that its role is to confer processivity on RNA-dependent RNA polymerase. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nsmb999) contains supplementary material, which is available to authorized users.