title: Arenavirus genetic diversity and its biological implications

text: Abstract The Arenaviridae family currently comprises 22 viral species, each of them associated with a rodent species. This viral family is important both as tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens. Arenaviruses are enveloped viruses with a bi-segmented negative-strand RNA genome. The interaction with the cellular receptor and subsequent entry into the host cell differs between Old World and New World arenavirus that use α-dystoglycan or human transferring receptor 1, respectively, as main receptors. The recent development of reverse genetic systems for several arenaviruses has facilitated progress in understanding the molecular biology and cell biology of this viral family, as well as opening new approaches for the development of novel strategies to combat human pathogenic arenaviruses. On the other hand, increased availability of genetic data has allowed more detailed studies on the phylogeny and evolution of arenaviruses. As with other riboviruses, arenaviruses exist as viral quasispecies, which allow virus adaptation to rapidly changing environments. The large number of different arenavirus host reservoirs and great genetic diversity among virus species provide the bases for the emergence of new arenaviruses potentially pathogenic for humans.


title: A neuropathic pain syndrome associated with hantavirus infection

text: Hantaviruses are a group of single-stranded RNA viruses of the Bunyaviridae family. “New World” hantaviruses cause hantavirus cardiopulmonary syndrome (HCPS) in North America. HCPS carries with it significant mortality and those patients who survive the disease are often left with substantial morbidity. Neurologic complications of hantavirus infections are rare, with only sparse cases of central nervous system involvement having been documented in the literature. To our knowledge, there are no reports of hantavirus infection contributing to peripheral nervous system dysfunction. Here we report a case of possible small fiber neuropathy associated with hantavirus infection, in a patient who survived HCPS. Persistent and treatment-resistant neuropathic pain may be a prominent feature in hantavirus-associated peripheral neuropathy.


title: Immunogenicity and protective efficacy of recombinant S1 domain of the porcine epidemic diarrhea virus spike protein

text: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. Acute PEDV outbreaks have continually emerged in most swine-producing Asian countries and, recently, in the United States, causing significant economic losses in the pig industry. The spike (S) protein of PEDV is a type 1 transmembrane envelope glycoprotein and consists of the S1 and S2 domains, which are responsible for virus binding and fusion, respectively. Since the S1 domain is involved in a specific high-affinity interaction with the cellular receptor and induction of neutralizing antibody in the natural host, it is a primary target for the development of effective vaccines against PEDV. In this study, a codon-optimized PEDV S1 gene containing amino acid residues 25–738 was synthesized based on a multiple alignment of the S amino acid sequences of PEDV field isolates and used to establish a stable porcine cell line constitutively expressing the PEDV S1 protein. The purified recombinant S1 protein was found to mediate highly potent antibody responses in immunized rabbits. The antibodies strongly recognized the recombinant S1 protein from cell lysates and supernatants of S1-expressing cells, whereas they bound weakly to the authentic S protein of PEDV vaccine strain SM98-1. Furthermore, a serum neutralization test revealed that the rabbit antisera completely inhibit infection of the PEDV vaccine strain at a serum dilution of 1:16. We then tested the ability of vaccination with the recombinant S1 protein to protect piglets against PEDV. Late-term pregnant sows were inoculated intramuscularly with the purified S1 protein, and the outcome was investigated in passively immunized suckling piglets after a virulent PEDV challenge. The results showed that vaccination with S1 protein efficiently protected neonatal piglets against PEDV. Our data suggest that the recombinant S1 protein shows potential as an effective and safe subunit vaccine for PED prevention.


title: Chiropractic students call for action against unsubstantiated claims

text: BACKGROUND: The 2019 coronavirus pandemic is a current global health crisis. Many chiropractic institutions, associations, and researchers have stepped up at a time of need. However, a subset of the chiropractic profession has claimed that spinal manipulative therapy (SMT) is clinically effective in improving one’s immunity, despite the lack of supporting scientific evidence. These unsubstantiated claims contradict official public health policy reflecting poorly on the profession. The aim of this commentary is to provide our perspective on the claims regarding SMT and clinically relevant immunity enhancement, drawing attention to the damaging ramifications these claims might have on our profession’s reputation. MAIN TEXT: The World Federation of Chiropractic released a rapid review demonstrating the lack of clinically relevant evidence regarding SMT and immunity enhancement. The current claims contradicting this review carry significant potential risk to patients. Furthermore, as a result of these misleading claims, significant media attention and public critiques of the profession are being made. We believe inaction by regulatory bodies will lead to confusion among the public and other healthcare providers, unfortunately damaging the profession’s reputation. The resulting effect on the reputation of the profession is greatly concerning to us, as students. CONCLUSION: It is our hope that all regulatory bodies will protect the public by taking appropriate action against chiropractors making unfounded claims contradicting public health policy. We believe it is the responsibility of all stakeholders in the chiropractic profession to ensure this is carried out and the standard of care is raised. We call on current chiropractors to ensure a viable profession exists moving forward.


title: Frequent respiratory viral infections in a young child in a 27-month follow-up study

text: INTRODUCTION: Viruses are major aetiological agents of acute respiratory infection in young children. Although many studies have reported detection and analysis of respiratory viruses in sporadic cases, there have been few follow-up studies of individuals. The purpose of this study was to investigate the frequency of respiratory viral infections in a young child and to examine the duration of viral genome detection in clinical specimens. CASE PRESENTATION: A total of 284 nasal swabs were collected during symptomatic (196 specimens) and asymptomatic (88 specimens) periods of respiratory symptoms from a young female child (from 4 months to 31 months of age, who was admitted to a nursery school at 9 months). Multiplex real-time PCR for 19 respiratory viruses or subtypes was performed. One hundred and ninety-eight of the tested specimens were virus positive (69.7 %) (symptomatic periods, 149/196, 76.0 %; asymptomatic periods, 49/88, 55.7 %). Rhinovirus was the most frequently detected (26 times). Long durations of detection were observed for human coronavirus NL63 (30 days), rhinovirus (28 days) and human bocavirus 1 (22 days). CONCLUSION: Young children living in a group context have a high risk of respiratory virus infections, especially rhinovirus. In some instances, viral genomes were detectable for about 1 month by PCR.


title: Mouse Hepatitis Virus Strain A59 RNA Polymerase Gene ORF 1a: Heterogeneity among MHV Strains

text: Abstract Gene 1, the putative RNA replicase gene of coronaviruses, is expressed via two large overlapping open reading frames (ORF 1a and ORF 1b). We have determined the nucleotide sequence of ORF 1a, encoded within the first 13.7 kb of gene 1, for the coronavirus mouse hepatitis virus strain A59 (MHV-AS9). Putative papain-like protease domains, a picornavirus 3C-like protease domain, two hydrophobic domains, and a domain "X" of unknown function, previously identified in other coronaviruses (1-3), are also present in ORF 1a of MHV-A59. Comparison between the ORF 1a sequence of MHV-A59 and the published sequence of the JHM strain of MHV (2) showed a high degree of similarity with the exception of several short regions. We sequenced one region of MHV-JHM that contained an 18 amino acid insertion relative to A59 and four other regions in which the sequences of the two strains differed. The MHV-2 and MHV-3 strains were else sequenced in some of these regions. Our analysis confirmed the presence of only one heterogeneous region in ORF 1a of MHV-A59 and MHV-JHM which is also present in MHV-2. Our findings indicate the need to modify the published sequence of MHV-JHM.


title: Some One Health based control strategies for the Middle East respiratory syndrome coronavirus

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) presents an ideal example for developing One Health concepts. Dromedary camels are the principal reservoir for the virus. Infected camels shed the virus in body secretions, particularly nasal discharges. MERS-CoV has the potential to remain active in the environment for some time under optimum conditions of temperature and humidity. This shedding sustains the virus in endemic communities and thus contact with camels is considered a major risk factor for human infection. Reducing virus shedding from camels will have a great positive impact on reducing the human risk of infection. Our main objective is to highlight the potential aspects of reducing virus shedding from camels to the environment, thereby reducing the possibility of human infection. We will focus on the potential roles of camel markets, camel shows, importation, transportation and grazing in the amplification and shedding of the virus, providing some novel concepts for the control approaches for the MERS-CoV.


title: Development of a duplex reverse transcription recombinase-aided amplification assay for respiratory syncytial virus incorporating an internal control

text: Human respiratory syncytial virus (RSV) is a common viral pathogen that causes lower respiratory tract infections in infants and children globally. In this study, we developed a duplex reverse transcription recombinase-aided amplification (duplex-rtRAA) assay containing an internal control in a single closed tube for the detection of human RSV. The internal control in the amplification effectively eliminated false-negative results and ensured the accuracy of the duplex-rtRAA system. We first developed and evaluated a universal singleplex-rtRAA assay for RSV. The sensitivity of this assay for RSV was determined as 4.4 copies per reaction, and the specificity was 100%. Next, a duplex-rtRAA assay with an internal control was established. The sensitivity of the duplex-rtRAA assay approached 5.0 copies per reaction, and no cross-reaction with other common respiratory viruses was observed. The two detection methods (singleplex-rtRAA and duplex-rtRAA) developed in this study were used to test 278 clinical specimens, and the results showed absolute consistency with RSV RT-qPCR analysis, demonstrating 100% diagnostic sensitivity and specificity. These data indicate that the duplex-rtRAA has great potential for the rapid detection of RSV with a high sensitivity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04230-z) contains supplementary material, which is available to authorized users.


title: Emerging and re-emerging coronaviruses in pigs

text: Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are emerging/reemerging coronaviruses (CoVs). They cause acute gastroenteritis in neonatal piglets. Sequence analyses suggest that PEDV and SADS-CoV may have originated from bat CoVs and PDCoV from a sparrow CoV, reaffirming the interspecies transmission of CoVs. The clinical signs and pathogenesis of the three viruses are similar. Necrosis of infected intestinal epithelial cells occurs, causing villous atrophy that results in malabsorptive diarrhea. The severe diarrhea and vomiting may lead to dehydration and death of piglets. Natural infection induces protective immunity, but there is no cross-protection among the three viruses. Besides strict biosecurity measures, individual vaccines are needed for each virus for disease prevention and control.


title: Seroepidemiology of Selected Alphaviruses and Flaviviruses in Bats in Trinidad

text: A serosurvey of antibodies against selected flaviviruses and alphaviruses in 384 bats (representing 10 genera and 14 species) was conducted in the Caribbean island of Trinidad. Sera were analysed using epitope‐blocking enzyme‐linked immunosorbent assays (ELISAs) specific for antibodies against West Nile virus (WNV), Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), all of which are zoonotic viruses of public health significance in the region. Overall, the ELISAs resulted in the detection of VEEV‐specific antibodies in 11 (2.9%) of 384 bats. Antibodies to WNV and EEEV were not detected in any sera. Of the 384 sera, 308 were also screened using hemagglutination inhibition assay (HIA) for antibodies to the aforementioned viruses as well as St. Louis encephalitis virus (SLEV; which also causes epidemic disease in humans), Rio Bravo virus (RBV), Tamana bat virus (TABV) and western equine encephalitis virus (WEEV). Using this approach, antibodies to TABV and RBV were detected in 47 (15.3%) and 3 (1.0%) bats, respectively. HIA results also suggest the presence of antibodies to an undetermined flavivirus(es) in 8 (2.6%) bats. Seropositivity for TABV was significantly (P < 0.05; χ(2)) associated with bat species, location and feeding preference, and for VEEV with roost type and location. Differences in prevalence rates between urban and rural locations were statistically significant (P < 0.05; χ(2)) for TABV only. None of the aforementioned factors was significantly associated with RBV seropositivity rates.


title: Virus Infection

text: Viruses are obligate intracellular parasites that can exist as potentially active but inert entities outside of cells. While there are viruses that infect many animal, plant, and protist cells and result in effects on the host that range from inapparent infection to lethality, all virus infections have some features in common. These include an entry phase, an intracellular phase consisting of multiplication, integration, or latency formation, a virus release phase, and usually some sort of host responses to the presence of the virus infection. It is often these host responses that appear as the most prominent signs and symptoms of virus infection.


title: Infectious bronchitis virus attaches to lipid rafts and enters cells via clathrin mediated endocytosis

text: Due to its economic importance to in poultry industry, the biology and pathogenesis of infectious bronchitis virus (IBV) have been investigated extensively. However, the molecular mechanisms involved in IBV entry are not well characterized. In this study, systematic approaches were used to dissect IBV entry process in various susceptible cells. First, we observed that lipid rafts were involved in IBV attachment. Second, low pH in intracyplasmic vesicles was required for virus entry. By using the specific clathrin mediated endocytosis (CME) inhibitor or knock down of clathrin heavy chain (CHC), we demonstrated that IBV mainly utilized the CME for its entry. Furthermore, GTPase dynamin1 was involved in virus containing vesicle scission and internalization. Surprisingly, CME adaptor Eps15 had no effect on IBV internalization. Third, the penetration of IBV into cells led to active cytoskeleton rearrangement. After internalization, virus particles moved along with the classical endosome/lysosome track, as evidenced by co-localization of R18 labeled IBV with vehicle markers Rab5/Rab7/LAMP1 along with the infection time course. Functional inactivation of Rab5 and Rab7 significantly inhibited IBV infection. VCP, a protein helps early endosome maturation, was involved virus trafficking. Finally, by using the dual R18/DiOC labeled IBV, we observed that membrane fusion with late endosome/lysosome membranes was induced between 2-3 h.p.i.. Taken together, our findings demonstrate that IBV virions attach to lipid rafts and are internalized into cells via CME, move along with early/late endosomes-lysosomes, finally fuse with late endosome-lysosome membranes, release virus genome into cytoplasm. This study provides comprehensive images of IBV attachment-internalization-trafficking-fusion steps. IMPORTANCE IBV, the avian coronavirus isolated in 1937, infects chicken and causes economic loss in poultry industry. It has been reported that the entry of IBV requires low pH. However, the molecular mechanisms underlying IBV internalization and trafficking remain to be clarified. Therefore, we employed multiple chemical and molecular approaches to dissect the entry mechanisms of IBV in susceptible cells. Our results showed IBV entry was significantly inhibited when clathrin-mediated endocytosis (CME) was blocked by chemical inhibitor or depletion of clathrin protein. Moreover, by using R18-labeled IBV, we found that IBV particles attached to lipid rafts, led to actin rearrangement, and moved along with the entire endosomal system. R18/DiOC labeling method showed that IBV fused with late endosomes or lysosomes. This is the first report to describe the entire entry process of IBV, allowing for a better understanding of the infection process of group III avian coronavirus.


title: Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection

text: Abstract A variety of both RNA and DNA viruses envelop their capsids in a lipid bilayer. One of the more recently appreciated benefits this envelope is incorporation of phosphatidylserine (PtdSer). Surface exposure of PtdSer disguises viruses as apoptotic bodies; tricking cells into engulfing virions. This mechanism is termed apoptotic mimicry. Several PtdSer receptors have been identified to enhance virus entry and we have termed this group of proteins PtdSer-mediated virus entry enhancing receptors or PVEERs. These receptors enhance entry of a range of enveloped viruses. Internalization of virions by PVEERs provides a broad mechanism of entry with little investment by the virus itself. PVEERs may allow some viruses to attach to cells, thereby making viral glycoprotein/cellular receptor interactions more probable. Alternatively, other viruses may rely entirely on PVEERs for internalization into endosomes. This review provides an overview of PtdSer receptors that serve as PVEERs and the biology behind virion/PVEER interaction.


Réflexions et perspectives sur les menaces infectieuses émergentes, à partir du séminaire du Val de Grâce de 7 décembre 2012, Paris


title: Converging and emerging threats to health security

text: Advances in biological sciences have outpaced regulatory and legal frameworks for biosecurity. Simultaneously, there has been a convergence of scientific disciplines such as synthetic biology, data science, advanced computing and many other technologies, which all have applications in health. For example, advances in cybercrime methods have created ransomware attacks on hospitals, which can cripple health systems and threaten human life. New kinds of biological weapons which fall outside of traditional Cold War era thinking can be created synthetically using genetic code. These convergent trajectories are dramatically expanding the repertoire of methods which can be used for benefit or harm. We describe a new risk landscape for which there are few precedents, and where regulation and mitigation are a challenge. Rapidly evolving patterns of technology convergence and proliferation of dual-use risks expose inadequate societal preparedness. We outline examples in the areas of biological weapons, antimicrobial resistance, laboratory security and cybersecurity in health care. New challenges in health security such as precision harm in medicine can no longer be addressed within the isolated vertical silo of health, but require cross-disciplinary solutions from other fields. Nor can they cannot be managed effectively by individual countries. We outline the case for new cross-disciplinary approaches in risk analysis to an altered risk landscape.


title: Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology

text: Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis.


title: Advancement and applications of peptide phage display technology in biomedical science

text: Combinatorial phage library is a powerful research tool for high-throughput screening of protein interactions. Of all available molecular display techniques, phage display has proven to be the most popular approach. Screening phage-displayed random peptide libraries is an effective means of identifying peptides that can bind target molecules and regulate their function. Phage-displayed peptide libraries can be used for (i) B-cell and T-cell epitope mapping, (ii) selection of bioactive peptides bound to receptors or proteins, disease-specific antigen mimics, peptides bound to non-protein targets, cell-specific peptides, or organ-specific peptides, and (iii) development of peptide-mediated drug delivery systems and other applications. Targeting peptides identified using phage display technology may be useful for basic research and translational medicine. In this review article, we summarize the latest technological advancements in the application of phage-displayed peptide libraries to applied biomedical sciences.


title: Polyols (Glycerol and Ethylene glycol) mediated amorphous aggregate inhibition and secondary structure restoration of metalloproteinase-conalbumin (ovotransferrin)

text: Abstract Under physical or chemical stress, proteins tend to form aggregates either highly ordered (amyloid) or unordered (amorphous) causing many pathological disorders in human and loss of proteins functionality in both laboratory conditions and industries during production and storage at commercial level. We investigated the effect of increasing temperature on Conalbumin (CA) and induced aggregation at 65°C. The enhanced Thioflavin T (ThT) and ANS (1-anilinonaphtalene 8-sulfonic acid) fluorescence intensity, show no shift on Congo red binding, additionally, transmission and scanning electron microscopy (TEM) (SEM) reveal amorphous morphology of the aggregate. Our investigation clearly demonstrated that polyols namely Glycerol (GL) and Ethylene glycol (EG) are so staunch to inhibit amorphous aggregates via restoring secondary conformation. Addition of polyols (15% GL and 35% EG) significantly decrease the turbidity, Rayleigh scattering ThT and ANS fluorescence intensity. The dynamic light scattering (DLS) data show that hydrodynamic radii (Rh) of the aggregates is ∼20 times higher than native CA while nearly similar for GL and EG protected CA due to condensation of core size with little difference.


title: Viral Membranes

text: Many viruses are surrounded by a continuous bilayer membrane studded with viral proteins. Its purpose is to protect the genome-containing virus nucleocapsid from damage, and to facilitate entry of the nucleocapsid into a host cell. Viral membrane proteins attach the virus to the host cell, and promote fusion between viral and host cell membranes. Enveloped viruses form by a budding process, involving the wrapping up of newly synthesized nucleocapsids with regions of host cell membranes containing host cell lipids but exclusively viral proteins. Host cell machinery and processes are co-opted by enveloped viruses for use at every stage of these viral events.


title: CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection

text: Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(−/−) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R.


title: Idiopathic AIDS Enteropathy and Treatment of Gastrointestinal Opportunistic Pathogens

text: Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients.


docid: unyukbfi

title: Treatment of a case presenting as critical adenoviral ARDS using Cidofovir with early combinatorial prone ventilation and ECMO

text: Here, we report a case of adenoviral pneumonia associated with critical ARDS treated with Cidofovir, prone ventilation and extracorporeal membrane oxygenation (ECMO). The patient responded well to therapy and recovered without further complications. Cidofovir, with early prone ventilation and ECMO support, may be a therapeutic option for patients with critical ARDS related to adenoviral pneumonia.


title: Geographical variations in COVID-19 Perceptions and Patient Management: A National Survey of Rheumatologists

text: OBJECTIVE: To investigate the perceptions and behaviors of rheumatologists in the United States (US) regarding the risk of COVID-19 for their autoimmune patients and the subsequent management of immunosuppressive and anti-inflammatory medications. METHODS: We administered an online survey to a convenience sample of rheumatologists in the US from 4/8/20-5/4/20 via social media and group emails. Survey respondents provided demographic information such as, age, gender, state of practice, and practice type. We asked questions about COVID-19 risk in rheumatic patients, as well as their medication management during the pandemic. We conducted descriptive analysis and Multivariable regression models. RESULTS: 271 respondents completed the survey nationally. 48% of respondents either agreed or strongly agreed with the statement “Patients with rheumatic diseases are at a higher risk of COVID-19 irrespective of their immunosuppressive medications”. 50% disagreed or strongly disagreed with the statement “The pandemic has led you to reduce the use/dosage/frequency of biologics”, while 56% agreed or strongly agreed with the statement “The pandemic has led you to reduce the use/dosage/frequency of steroids”. A third of respondents indicated that at least 10% of their patients had self-discontinued or reduced at least one immunosuppressive medication to mitigate their risk of COVID-19. Responses to these questions as well as to questions regarding NSAID prescription patterns were significantly different in the Northeast region of US compared to other regions. CONCLUSION: In this national sample of rheumatologists, there are variations regarding perceptions of patients’ risk of COVID-19, and how to manage medications such as NSAIDs, biologics and steroids during the pandemic. These variations are more pronounced in geographical areas where COVID-19 disease burden was high.


title: Characteristics and trends of traumatic injuries in children visiting emergency departments in South Korea: A retrospective serial cross-sectional study using both nationwide-sample and single-institutional data

text: We investigated the incidences and characteristics of pediatric traumatic injuries requiring emergency department visits, through a complementary approach using both nationwide-sample and single-institutional data. Data for children (aged <15 years) identified with traumatic injuries during a 10-year period from the Korean National Health Insurance Sharing Service (n = 35,064 among 10,114,909 randomly sampled cases from the claim records of the National Health Insurance) and the authors' institute (n = 39,228) were retrospectively reviewed. The incidences and characteristics of the injuries were investigated using both datasets; additionally, detailed information regarding the injury environments was investigated using the single-institutional data. The findings were similar across both datasets. The incidence of injuries increased during the study period; the head was most commonly injured, whereas the trunk or proximal extremities were rarely injured; low-energy head injuries accounted for >50% of the cases in children aged <5 years, although the incidences of lower-extremity injuries and fractures increased in older children. Single-institutional data demonstrated that the proportion of indoor playground and trampoline-related injuries increased rapidly during the study period, and outdoor injuries and seasonal variation (with peak incidences in May and June) were more prominent in older children. Based on similarities between both datasets, the detailed results regarding pediatric traumatic injuries obtained from the single-institutional data could be generalized nationally with adequate external validity. To prevent traumatic injuries, it may be more effective to wear protective equipment covering the head and distal extremities rather than the trunk or proximal extremities; simple clothing, such as caps, could prevent many injuries in preschoolers. Among older children, safety guidelines for outdoor sports/leisure activities are needed. The increase in pediatric traumatic injuries may be partially explained by the increased availability of indoor playgrounds and installation of trampolines. Stricter adherence to the preventive guidelines is needed.


title: Development of Recombinant Measles Virus-Based Vaccines

text: This chapter describes the development of recombinant measles virus (MV)-based vaccines starting from plasmid DNA. Live-attenuated measles vaccines are very efficient and safe. Since the availability of a reverse genetic system to manipulate MV genomes and to generate respective recombinant viruses, a considerable number of recombinant viruses has been generated that present antigens of foreign pathogens during MV replication. Thereby, robust humoral and cellular immune responses can be induced, which have shown protective capacity in a substantial number of experiments. For this purpose, the foreign antigen-encoding genes are cloned into additional transcription units of plasmid based full-length MV vaccine strain genomes, which in turn are used to rescue recombinant MV by providing both full-length viral RNA genomes respective anti-genomes together with all protein components of the viral ribonucleoprotein complex after transient transfection of the so-called rescue cells. Infectious centers form among these transfected cells, which allow clonal isolation of single recombinant viruses that are subsequently amplified, characterized in vitro, and then evaluated for their immunogenicity in appropriate preclinical animal models.


title: The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data

text: BACKGROUND: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. METHODOLOGY/PRINCIPAL FINDINGS: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. CONCLUSIONS/SIGNIFICANCE: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.


title: The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation

text: Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein–protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, implicating ADP-ribosylation in the host defense response and suggesting that viral macrodomains may counter this response. Recent studies have demonstrated that viral macrodomains do counter the innate immune response by interfering with PARP-mediated antiviral defenses, stress granule formation, and pro-inflammatory cytokine production. Here, we will describe the known functions of the viral macrodomains and review recent literature demonstrating their roles in countering PARP-mediated antiviral responses.


title: Pixelated colorimetric nucleic acid assay

text: Abstract Conjugated polyelectrolytes (CPEs) have been widely used as reporters in colorimetric assays targeting nucleic acids. CPEs provide naked eye detection possibility by their superior optical properties however, as concentration of target analytes decrease, trace amounts of nucleic acid typically yield colorimetric responses that are not readily perceivable by naked eye. Herein, we report a pixelated analysis approach for correlating colorimetric responses of CPE with nucleic acid concentrations down to 1 nM, in plasma samples, utilizing a smart phone with an algorithm that can perform analytical testing and data processing. The detection strategy employed relies on conformational transitions between single stranded nucleic acid-cationic CPE duplexes and double stranded nucleic acid-CPE triplexes that yield distinct colorimetric responses for enabling naked eye detection of nucleic acids. Cationic poly[N,N,N-triethyl-3-((4-methylthiophen-3-yl)oxy)propan-1-aminium bromide] is utilized as the CPE reporter deposited on a polyvinylidene fluoride (PVDF) membrane for nucleic acid assay. A smart phone application is developed to capture and digitize the colorimetric response of the individual pixels of the digital images of CPE on the PVDF membrane, followed by an analysis using the algorithm. The proposed pixelated approach enables precise quantification of nucleic acid assay concentrations, thereby eliminating the margin of error involved in conventional methodologies adopted for interpretation of colorimetric responses, for instance, RGB analysis. The obtained results illustrate that a ubiquitous smart phone could be utilized for point of care colorimetric nucleic acids assays in complex matrices without requiring sophisticated software or instrumentation.


title: Analysis of intracellular small RNAs of mouse hepatitis virus: evidence for discontinuous transcription

text: Abstract We have previously shown the presence of multiple small leader-containing RNA species in mouse hepatitis virus (MHV)-infected cells. In this paper, we have analyzed the origin, structure, and mechanism of synthesis of these small RNAs. Using cDNA probes specific for leader RNA and genes A, D, and F, we demonstrate that subsets of these small RNAs were derived from the various viral genes. These subsets have discrete and reproducible sizes, varying with the gene from which they are derived. The size of each subset correlates with regions of secondary structure, whose free energy ranges from −1.6 to −77.1 kcal/mol, in each of the mRNAs examined. In addition, identical subsets were detected on the replicative intermediate (RI) RNA, suggesting that they represent functional transcriptional intermediates. The biological significance of these small RNAs is further supported by the detection of leader-containing RNAs of 47, 50, and 57 nucleotides in length, which correspond to the crossover sites in two MHV recombinant viruses. These data, coupled with the high frequency of RNA recombination during MHV infection, suggest that the viral polymerase may pause in or around regions of secondary structure, thereby generating pools of free leader-containing RNA intermediates which can reassociate with the template, acting as primers for the synthesis of full-length or recombinant RNAs. These data suggest that MHV transcription uses a discontinuous and nonprocessive mechanism in which RNA polymerase allows the partial RNA products to be dissociated from the template temporarily during the process of transcription.


title: Multimodal Emotion Evaluation: A Physiological Model for Cost-Effective Emotion Classification

text: Emotional responses are associated with distinct body alterations and are crucial to foster adaptive responses, well-being, and survival. Emotion identification may improve peoples’ emotion regulation strategies and interaction with multiple life contexts. Several studies have investigated emotion classification systems, but most of them are based on the analysis of only one, a few, or isolated physiological signals. Understanding how informative the individual signals are and how their combination works would allow to develop more cost-effective, informative, and objective systems for emotion detection, processing, and interpretation. In the present work, electrocardiogram, electromyogram, and electrodermal activity were processed in order to find a physiological model of emotions. Both a unimodal and a multimodal approach were used to analyze what signal, or combination of signals, may better describe an emotional response, using a sample of 55 healthy subjects. The method was divided in: (1) signal preprocessing; (2) feature extraction; (3) classification using random forest and neural networks. Results suggest that the electrocardiogram (ECG) signal is the most effective for emotion classification. Yet, the combination of all signals provides the best emotion identification performance, with all signals providing crucial information for the system. This physiological model of emotions has important research and clinical implications, by providing valuable information about the value and weight of physiological signals for emotional classification, which can critically drive effective evaluation, monitoring and intervention, regarding emotional processing and regulation, considering multiple contexts.


title: Computational Approaches to Influenza Surveillance: Beyond Timeliness

text: Several digital data sources and systems have been advanced for use in augmenting traditional influenza surveillance systems. Although timeliness is one of the main advantage of these tools, there are several other recognizable uses and potential impact of these systems on the public and global public health.


title: Directional Airflow and Ventilation in Hospitals: A Case Study of Secondary Airborne Infection

text: Abstract Since the 1990s, improvements in ventilation techniques and isolation procedures have been widely credited with the decline in nosocomial transmission of tuberculosis and other airborne diseases. Little effort, however, has been made to study the risk of isolation patients acquiring secondary infections from contaminated air migrating into negatively pressurized isolation rooms from adjacent spaces. As a result, an actual hospital was used to observe the transport of aerosol from a nursing station and general patient room to a nearby airborne infectious isolation room (AIIR). Aerosols ≤3.0μm (viruses and most airborne bacteria) were found to be capable of migrating 14.5m from a general patient room to an AIIR anteroom entrance in <14minutes at concentrations 2-5 times greater than ambient (e.g. background). Concentrations of aerosols within the anteroom and isolation room, however, remained virtually unchanged from ambient levels, indicating the effectiveness of door position and (or) ventilation. In contrast, gravitational settling and surface deposition appeared to limit the migration of aerosols >3.0μm to the entrance of the general patient room (4.5m).


title: Griffithsin inhibits Japanese encephalitis virus infection in vitro and in vivo

text: Griffithsin (GRFT) is a broad-spectrum antiviral protein that is effective against several glycosylated viruses. Here, we have evaluated the in vitro and in vivo antiviral activities of GRFT against Japanese encephalitis virus (JEV) infection. In vitro experiments showed that treatment of JEV with GRFT before inoculation of BHK-21 cells inhibited infection in a dose-dependent manner, with 99 % inhibition at 100 μg/ml and a 50 % inhibitory concentration (IC(50)) of 265 ng/ml (20 nM). Binding assays suggested that binding of GRFT to JEV virions inhibited JEV infection. In vivo experiment showed that GRFT (5 mg/kg) administered intraperitoneally before virus infection could completely prevent mortality in mice challenged intraperitoneally with a lethal dose of JEV. Our study also suggested that GRFT prevents JEV infection at the entry phase by targeting the virus. Collectively, our data demonstrate that GRFT is an antiviral agent with potential application in the development of therapeutics against JEV or other flavivirus infections.


title: Three-dimensional visualization of the rotavirus hemagglutinin structure

text: Abstract Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. Exchange of native VP4 with a bovine strain equivalent results in a poorly infectious reassortant. No VP4 spikes are detected in the three-dimensional reconstruction of the reassortant. The difference map between the two structures reveals a novel large globular domain of VP4 buried within the virion that interacts extensively with the intermediate shell protein, VP6. Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation.


title: The impacts of simultaneous disease intervention decisions on epidemic outcomes

text: Abstract Mathematical models of the interplay between disease dynamics and human behavioural dynamics can improve our understanding of how diseases spread when individuals adapt their behaviour in response to an epidemic. Accounting for behavioural mechanisms that determine uptake of infectious disease interventions such as vaccination and non-pharmaceutical interventions (NPIs) can significantly alter predicted health outcomes in a population. However, most previous approaches that model interactions between human behaviour and disease dynamics have modelled behaviour of these two interventions separately. Here, we develop and analyze an agent based network model to gain insights into how behaviour toward both interventions interact adaptively with disease dynamics (and therefore, indirectly, with one another) during the course of a single epidemic where an SIRV infection spreads through a contact network. In the model, individuals decide to become vaccinated and/or practice NPIs based on perceived infection prevalence (locally or globally) and on what other individuals in the network are doing. We find that introducing adaptive NPI behaviour lowers vaccine uptake on account of behavioural feedbacks, and also decreases epidemic final size. When transmission rates are low, NPIs alone are as effective in reducing epidemic final size as NPIs and vaccination combined. Also, NPIs can compensate for delays in vaccine availability by hindering early disease spread, decreasing epidemic size significantly compared to the case where NPI behaviour does not adapt to mitigate early surges in infection prevalence. We also find that including adaptive NPI behaviour strongly mitigates the vaccine behavioural feedbacks that would otherwise result in higher vaccine uptake at lower vaccine efficacy as predicted by most previous models, and the same feedbacks cause epidemic final size to remain approximately constant across a broad range of values for vaccine efficacy. Finally, when individuals use local information about others’ behaviour and infection prevalence, instead of population-level information, infection is controlled more efficiently through ring vaccination, and this is reflected in the time evolution of pair correlations on the network. This model shows that accounting for both adaptive NPI behaviour and adaptive vaccinating behaviour regarding social effects and infection prevalence can result in qualitatively different predictions than if only one type of adaptive behaviour is modelled.


Why your Patients’ Believing Hydroxychloroquine and Chloroquine are 90% Effective for COVID‐19 is 100% Dangerous


What’s Important: Facing Fear in the Time of COVID-19


title: Human polymicrobial infections

text: Summary Context Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. Starting point Recently, Gili Regev-Yochay (JAMA 2004; 292: 716–20) and Debby Bogaert (Lancet 2004; 363: 1871–72), and their colleagues, suggested another interaction: microbial interference—the ability of Streptococcus pneumoniae carriage to protect against Staphylococcus aureus carriage, and the inverse effect of pneumococcal conjugate vaccination on the increased carriage of Staph aureus and Staph-aureus-related disease. Strep pneumoniae carriage protected against Staph aureus carriage, and the bacterial interference could be disrupted by vaccinating children with pneumococcal conjugate vaccines that reduced nasopharyngeal carriage of vaccine-type Strep pneumoniae. Where next The medical community is recognising the significance of polymicrobial diseases and the major types of microbial community interactions associated with human health and disease. Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention.


docid: bzsvuwyl

title: Chapter 66 Transfusion Transmitted Diseases

text: Publisher Summary This chapter discusses the various diseases transmitted by blood transfusion. This transfusion transmitted diseases (TTD) can be caused by viruses, protozoa and prions. The mitigation of transfusion transmission of infectious agents is mentioned to be based on donor selection and donor testing. A table is presented that illustrates the potential transfusion transmitted agents. Hepatitis viruses are transmitted through transfusion and result in inflammation of the liver, jaundice, hepatomegaly and anorexia and both hepatitis B and hepatitis C typical hepatitis viruses transmitted through transfusion. Several other viruses transmitted through transfusion of infected blood include human immunodeficiency virus, human t-cell lymphotropic virus and herpesviruses. The protozoans transmitted due to transfusion include Plasmodium, Trypanosoma and Leishmania. Prion diseases results from the benign form of the prion protein changing to an insoluble protease-resistant form, which leads to the formation of plagues in the brain. Another transfusion transmitted disease called transmissible spongiform encephalopathies (Creutzfeldt-Jakob disease) is described.


title: COVID-19 from the land “Down Under” in an upside-down world: an Australian perspective

text: Australia's approach to the current COVID-19 pandemic has resulted in relative containment of the disease. However, it must be remembered that any defence is only as strong as its weakest link.


title: Les infections à coronavirus humains

text: Résumé Les coronavirus humains (HCoV) sont des virus à ARN simple brin. Il existe actuellement quatre coronavirus dits « classiques » ou « nouveaux », dont la circulation est hivernale. Ils sont à l’origine d’infections respiratoires modérées dans la population générale. Cependant, les infections peuvent être plus sévères dans les populations susceptibles. Notamment, les HCoV sont impliqués dans 2 à 7% des hospitalisations consécutives à une infection respiratoire, en particulier chez les enfants et les personnes âgées ou immunodéprimées. De ce fait, ils appartiennent au panel de virus respiratoires recherchés lors des diagnostics de routine des infections respiratoires par des outils de biologie moléculaire. Ces coronavirus dits circulants sont à distinguer des deux coronavirus émergents, le SARS-CoV et le MERS-CoV qui sont associés à des pathologies respiratoires plus sévères. Ils se distinguent des autres HCoV par leur potentiel épidémique plus élevé, leur impact sanitaire plus important et leur mode de circulation atypique. À l’instar des paramyxovirus et des virus Influenza, les coronavirus doivent être surveillés pour leur risque d’émergence dans la population humaine à partir d’un réservoir animal. Summary Human coronaviruses (HCoV) are single strand RNA viruses. To date, there are four so-called « classical » or « novel » HCoVs, characterized by a winter circulation. These coronaviruses are responsible for mild respiratory infection in general population. However, HCoVs are associated to more severe respiratory tract infection among susceptible population. Indeed, HCoVs account for 2 to 7% of hospitalizations due to a respiratory infection, particularly among children, immunocompromised or elderly people. Thereby, HCoVs are included in the panel of respiratory viruses detected in routine using molecular biology tools. These four circulating HCoVs have to be distinguished from the two emerging HCoVs: SARS-CoV and MERS-CoV. These later are associated to a more severe respiratory infection and differ from other HCoVs by their increased epidemic potential, their more important health impact, and their atypical circulation. Such as paramyxoviruses and Influenza viruses, coronaviruses have to be monitored due to their associated risk of emergence in human population from animal reservoirs.


title: Emerging viral threats to the Australian blood supply

text: Objectives: To assess the risk to the Australian blood supply posed by emerging or re‐emerging viral infections. Method: A review was undertaken of the English‐speaking literature on the potential for emerging viral threats to human health in Australia, the future implications of virus ecology, climate change and population movement and the implications for blood transfusion. Results: Published data confirm that Australia's blood supply is among the safest in the world for currently screened viral pathogens as a result of rigorous surveillance, donor selection and state‐of‐the‐art processing and laboratory testing. However, Australia has a number of other viral pathogens with the potential to threaten the safety of the blood supply such as the Ross River, Barmah Forrest, Kunjin, Japanese Encephalitis, Murray Valley Encephalitis and dengue viruses. Of these, dengue is currently of most concern to blood safety because; it can cause fatalities, there are regular seasonal outbreaks in Northern Australia and, in contrast to other viruses mentioned above an overseas case of transfusion transmission has already been documented. Notably, despite the lack of a suitable dengue screening test the ARCBS already implements supplementary measures to protect the blood supply during outbreaks. Conclusion: Current interventions have proven extremely effective in minimising transfusion transmission in Australia of recognised viral pathogens. The threat posed by emerging viral pathogens to the safety of blood transfusion emphasises the need for global collaboration and consideration of further intervention strategies on a country by country basis including options such as nucleic acid testing and pathogen reduction technologies.


title: Conventional and molecular diagnostic testing for the acute neurologic patient

text: Objective – The aim of this review is to describe and evaluate both conventional and molecular diagnostic testing utilized in dogs and cats with acute neurologic diseases. Various types of polymerase chain reaction (PCR) are explored along with novel molecular diagnostic testing that ultimately may prove useful in the critical care setting. Data Sources – PUBMED was searched to obtain relevant references material using keywords: ‘canine OR feline meningitis AND meningoencephalitis,’‘feline infectious peritonitis,’‘canine distemper,’‘canine OR feline AND toxoplasma,’‘canine neospora,’‘canine OR feline AND rickettsia,’‘granulomatous meningoencephalitis,’‘steroid responsive meningitis arteritis,’‘necrotizing encephalitis,’‘novel neurodiagnostics,’‘canine OR feline AND CNS borrelia,’‘canine OR feline AND CNS bartonella,’‘canine OR feline AND CNS fungal,’‘nested OR multiplex OR degenerate OR consensus OR CODEHOP AND PCR.’ Research findings from the authors' laboratory and current veterinary textbooks also were utilized. Human Data Synthesis – Molecular diagnostic testing including conventional, real‐time, and consensus and degenerate PCR and microarray analysis are utilized routinely for the antemortem diagnosis of infectious meningoencephalitis (ME) in humans. Recently, PCR using consensus degenerate hybrid primers (CODEHOP) has been used to identify and characterize a number of novel human viruses. Veterinary Data Synthesis – Molecular diagnostic testing such as conventional and real‐time PCR aid in the diagnosis of several important central nervous system infectious agents including canine distemper virus, Toxoplasma gondii, Neospora caninum, rickettsial species, and others. Recently, broadly reactive consensus and degenerate PCR reactions have been applied to canine ME including assays for rickettsial organisms, Borrelia spp. and Bartonella spp., and various viral families. Conclusions – In the acute neurologic patient, there are several key infectious diseases that can be pursued by a combination of conventional and molecular diagnostic testing. It is important that the clinician understands the utility, as well as the limitations, of the various neurodiagnostic tests that are available.


title: A variant in the CD209 promoter is associated with severity of dengue disease

text: Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell–specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells(1,2). Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 × 10(−7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 × 10(−6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ng1550) contains supplementary material, which is available to authorized users.


title: Intraviral interactome of Chikungunya virus reveals the homo-oligomerization and palmitoylation of structural protein TF

text: Abstract Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. Although the protein-protein interactions (PPIs) between nonstructural proteins of CHIKV have been extensively established, the complete CHIKV intraviral interactome remains to be elucidated. In this study, we examined all possible CHIKV intraviral PPIs by immunoprecipitation and constructed the intraviral interactome of CHIKV. We reported 19 novel PPIs including the homo-oligomerization of TF. Disulfide bonds promoted the oligomerization of CHIKV TF protein. 2-BP, a palmitoylation inhibitor reduced the palmitoylation of TF and increased TF oligomerization. A quadruple mutant of Cys33, Cys35, Cys41, and Cys43 in TF blocked its palmitoylation and reduced oligomerization. Furthermore, we determined the association of TF with nsP1 and nsP3 in a palmitoylation-dependent manner. Construction of intraviral interactome of CHIKV provides the basis for further studying the function of CHIKV proteins.


title: The 2019‐new coronavirus epidemic: Evidence for virus evolution

text: There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.


title: Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus

text: Abstract Under laboratory conditions coronaviruses were shown to have a high frequency of recombination. In The Netherlands, vaccination against infectious bronchitis virus (IBV) is performed with vaccines that contain several life-attenuated virus strains. These highly effective vaccines may create ideal conditions for recombination, and could therefore be dangerous in the long term. This paper addresses the question of the frequency of recombination of avian coronavirus IBV in the field. A method was sought to detect and quantify recombination from sequence data. Nucleotide sequences of eight IBV isolates in a region of the genome suspected to contain recombination, were aligned and compared. Phylogenetic trees were constructed for different sections of this region. Differences in topology between these trees were observed, suggesting that in three out of eight strains in vivo RNA recombinant had occurred.


COVID-19 outbreak situation and its psychological impact among surgeon in training in France


Antigen-presenting properties of gingival fibroblasts in chronic adult periodontitis


title: The structural basis of paramyxovirus invasion

text: To deliver their genetic material into host cells, enveloped viruses have surface glycoproteins that actively cause the fusion of the viral and cellular membranes. Recently determined X-ray crystal structures of the paramyxovirus fusion (F) protein in its pre-fusion and post-fusion conformations reveal the dramatic structural transformation that this protein undergoes while causing membrane fusion. Conformational changes in key regions of the F protein suggest the mechanism by which the F protein is activated and refolds.


title: SARS-CoV-2 infection: the role of cytokines in COVID-19 disease

text: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.


docid: hsbjbwpa

title: An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics

text: Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.


title: Combination of Serological Total Antibody and RT-PCR Test for Detection of SARS-CoV-2 Infections

text: The purpose of this study was to investigate the feasibility of serological total antibody tests combined with RT-PCR for detection of SARS-CoV-2. We conducted a retrospective study in which 375 patients were enrolled during the outbreak of SARS-CoV-2 from 25th January to 16th March 2020. Patients were divided into a COVID-19 group (n = 141) and a control group (n = 234). Serum samples and throat swabs were collected from 375 patients for total antibody testing against SARS-CoV-2 and RT-PCR analysis, respectively. The results indicated that diagnostic sensitivity and specificity were 95.7% and 98.7%, 92.2% and 100% by total antibody tests and RT-PCR, respectively. The sensitivity and specificity of total antibody tests combined with RT-PCR were 98.6% and 98.7%. The sensitivity of the combined method was significantly higher than RT-PCR (X(2) = 5.16, P < 0.05), and similar to that of total antibody tests (X(2) = 1.15, P > 0.05). This study supported the advantage of the combined method for detection of SARS-CoV-2 with a high degree of sensitivity and specificity, as a useful tool for accurate diagnosis and timely treatment of suspected patients, epidemiological investigation, as well as monitoring ongoing outbreaks of infections with SARS-CoV-2.


APPROACH TO SURGICAL INTERVENTIONS DURING COVID-19 PANDEMIC IN TURKEY


title: Structural Basis of Ubiquitin Recognition by the Deubiquitinating Protease USP2

text: Summary Deubiquitinating proteases reverse protein ubiquitination and rescue their target proteins from destruction by the proteasome. USP2, a cysteine protease and a member of the ubiquitin specific protease family, is overexpressed in prostate cancer and stabilizes fatty acid synthase, which has been associated with the malignancy of some aggressive prostate cancers. Here, we report the structure of the human USP2 catalytic domain in complex with ubiquitin. Ubiquitin uses two major sites for the interaction with the protease. Both sites are required simultaneously, as shown by USP2 inhibition assays with peptides and ubiquitin mutants. In addition, a layer of ordered water molecules mediates key interactions between ubiquitin and USP2. As several of those molecules are found at identical positions in the previously solved USP7/ubiquitin-aldehyde complex structure, we suggest a general mechanism of water-mediated ubiquitin recognition by USPs.


title: Development and Evaluation of a SYBR Green–Based Real-Time Multiplex RT-PCR Assay for Simultaneous Detection and Serotyping of Dengue and Chikungunya Viruses

text: Chikungunya virus (CHIKV) and dengue virus (DENV) have emerged as the two most important arbovirus diseases of global health significance. Similar clinical manifestations, transmission vectors, geographical distribution, and seasonal correlation often result in misdiagnosis of chikungunya infections as dengue cases and vice versa. In this study, we developed a rapid and accurate laboratory confirmative method to simultaneously detect, quantify, and differentiate DENV serotypes 1, 2, 3, and 4 and CHIKV. This SYBR Green I–based one-step multiplex real-time RT-PCR assay is highly sensitive and specific for CHIKV and DENV. Melting temperature analysis of PCR amplicons was used to serotype DENV and to differentiate from CHIKV. The detection limit of the assay was 20, 10, 50, 5, and 10 RNA copies/reaction for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV, respectively. Our assay did not cross-react with a panel of viruses that included other flaviviruses, alphaviruses, influenza viruses, human enteroviruses, and human coronaviruses. The feasibility of using this assay for clinical diagnosis was evaluated in DENV- and CHIKV-positive patient sera. Accordingly, the assay sensitivity for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV was 89.66%, 96.67%, 96.67%, 94.12%, and 95.74%, respectively, with 100% specificity. These findings confirmed the potential of our assay to be used as a rapid test for simultaneous detection and serotyping of DENV and CHIKV in clinical samples.


title: Exploratory studies on the therapeutic effects of Kumarabharana Rasa in the management of chronic tonsillitis among children at a tertiary care hospital of Karnataka

text: Abstract The effect of an Ayurvedic poly-herbo-mineral formulation Kumarabharana Rasa (KR) in the management of chronic tonsillitis (Tundikeri) in children has been assessed in this study. This clinical study was a double-arm study with a pre- and post-test design at the outpatient level in a tertiary Ayurveda hospital attached to a teaching institute located in district headquarters in Southern India. Patients (n = 40) with chronic tonsillitis satisfying diagnostic criteria and aged between 5 and 10 years were selected from the outpatient Department of Kaumarbhritya, SDM College of Ayurveda and Hospital, Hassan. Among them, 20 patients were treated with Kumarabharana rasa (tablet form) at a dose of 500 mg once daily for 30 days (Group A). The other 20 patients were treated with Godhuma Vati (placebo) at a dose of 500 mg once daily for 30 days (Group B). In both groups, Madhu was the Anupana advised. After completion of 30 days of treatment, the patients were assessed on the following day and another investigation took place 15 days later. Statistically significant effects (p < 0.05) in the reduction of all signs and symptoms of chronic tonsillitis after KR treatment were observed. These results indicate that Kumarabharana Rasa has an ameliorative effect in reducing the signs and symptoms of chronic tonsillitis.


title: Bat adeno-associated viruses as gene therapy vectors with the potential to evade human neutralizing antibodies

text: The prevalence of adeno-associated virus (AAV) has been investigated in bat populations, but little is known about the biological properties of this virus. In this study, four full-length bat AAV capsid genes were isolated in China, with their amino acid sequences sharing 61% identity with those of AAV2 on average. These capsid genes could package AAV particles in combination with AAV2 rep and ITRs, albeit at a lower efficiency. Bat AAVs could only slightly infect mouse liver but could transduce mouse muscle to some extent after systemic administration with a higher muscle/liver ratio than that of primate AAVs. Bat AAV 10HB showed moderate muscle transduction, similar to that of AAV2, during direct intramuscular injection and, compared with other AAV serotypes, was also relatively efficient in resisting human antibody neutralization after intramuscular injection. Evolutionary analysis revealed a number of codons in bat AAV capsid genes subject to positive selection, with sites corresponding to V259 and N691 in 10HB capsids being localized on the surface of the AAV2 capsid. Mutagenesis studies indicated that the positive selection in bat AAV capsids is driven by their tropism evolution in host species. Taken together, the results of this study indicate that bat AAV 10HB vector has the possible applications for muscular gene therapy, especially in the presence of human AAV neutralizing antibodies.


Online-Only Abstracts These articles are available online at wileyonlinelibrary.com


title: The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis

text: Abstract Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection. In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling. We summarize work from our group and others indicating that inhibiting EGFR signaling may prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections and propose directions for future research.


title: Functional assessment and function‐based treatment delivered via telehealth: A brief summary

text: As the world navigates the COVID‐19 health crisis, behavior analysts are considering how best to support families while maintaining services and ensuring the health and safety of everyone involved. Telehealth is one service delivery option that provides families with access to care in their own communities and homes. In this article, we provide a brief summary of the telehealth literature in applied behavior analysis that provided coaching and training to families for individuals who displayed challenging behavior. These studies targeted functional assessment and function‐based treatment for challenging behavior. We briefly summarize what is known relative to the assessment and treatment of challenging behavior via telehealth, place these results within a descriptive context of the decisions made by the research team at the University of Iowa, and discuss what we, as behavior analysts, should consider next to advance our understanding and practice of telehealth.


DPP4-directed therapeutic strategies for MERS-CoV


title: The exposome in the community

text: The exposome is a complicated scientific research topic but an easily understandable concept for health. By integrating multiple external forces that act upon us, it is possible to take a holistic view of our health. The exposome model provides a way to organize and integrate the many new challenges we face in our day-to-day lives. This chapter provides examples of how the exposome can be incorporated into the lives of our families, communities, and countries, including educating the public across multiple sectors. The reader will find simple and scientifically sound recommendations for reducing chemical exposures and improving one’s exposome. Since one’s genome is relatively fixed, an improvement in one’s exposome will undoubtedly lead to an improvement in one’s health.


title: Loss of the Drosophila melanogaster DEAD box protein Ddx1 leads to reduced size and aberrant gametogenesis

text: Abstract Mammalian DDX1 has been implicated in RNA trafficking, DNA double-strand break repair and RNA processing; however, little is known about its role during animal development. Here, we report phenotypes associated with a null Ddx1 (Ddx1 AX ) mutation generated in Drosophila melanogaster. Ddx1 null flies are viable but significantly smaller than control and Ddx1 heterozygous flies. Female Ddx1 null flies have reduced fertility with egg chambers undergoing autophagy, whereas males are sterile due to disrupted spermatogenesis. Comparative RNA sequencing of control and Ddx1 null third instars identified several transcripts affected by Ddx1 inactivation. One of these, Sirup mRNA, was previously shown to be overexpressed under starvation conditions and implicated in mitochondrial function. We demonstrate that Sirup is a direct binding target of Ddx1 and that Sirup mRNA is differentially spliced in the presence or absence of Ddx1. Combining Ddx1 null mutation with Sirup dsRNA-mediated knock-down causes epistatic lethality not observed in either single mutant. Our data suggest a role for Drosophila Ddx1 in stress-induced regulation of splicing.


title: Bronchiectasis and cough: An old relationship in need of renewed attention

text: Abstract Bronchiectasis is an increasingly recognised respiratory condition with limited therapeutic options and a complex spectrum of clinical manifestations that invariably includes chronic cough. As the primary presentation of bronchiectasis in most cases, chronic cough and its mechanistic underpinnings are of central importance but remain poorly understood in this setting. Bronchiectasis is also increasingly identified as an underlying cause of chronic cough highlighting the interrelationship between the two conditions that share overlapping clinical features. Several therapeutic approaches have illustrated positive effects on bronchiectasis-associated cough, however, more focused treatment of heterogeneous cough subtypes may yield better outcomes for patients. A current challenge is the identification of bronchiectasis and cough endophenotypes that may allow improved patient stratification and more targeted therapeutic matching of the right treatment to the right patient. Here we discuss the complex disease phenotypes of bronchiectasis and their interrelationship with cough while considering current and emerging treatment options. We discuss some key cough promoters in bronchiectasis including infection, allergy and immune dysfunction.


title: F4-related mutation and expression analysis of the aminopeptidase N gene in pigs(1)

text: Intestinal infections with F4 enterotoxigenic Escherichia coli (ETEC) are worldwide an important cause of diarrhea in neonatal and recently weaned pigs. Adherence of F4 ETEC to the small intestine by binding to specific receptors is mediated by F4 fimbriae. Porcine aminopeptidase N (ANPEP) was recently identified as a new F4 receptor. In this study, 7 coding mutations and 1 mutation in the 3′ untranslated region (3' UTR)were identified in ANPEP by reverse transcriptase (RT–) PCR and sequencing using 3 F4 receptor-positive (F4R+) and 2 F4 receptor-negative (F4R–) pigs, which were F4 phenotyped based on the MUC4 TaqMan, oral immunization, and the in vitro villous adhesion assay. Three potential differential mutations (g.2615C > T, g.8214A > G, and g.16875C > G) identified by comparative analysis between the 3 F4R+ and 2 F4R– pigs were genotyped in 41 additional F4 phenotyped pigs. However, none of these 3 mutations could be associated with F4 ETEC susceptibility. In addition, the RT-PCR experiments did not reveal any differential expression or alternative splicing in the small intestine of F4R+ and F4R– pigs. In conclusion, we hypothesize that the difference in F4 binding to ANPEP is due to modifications in its carbohydrate moieties.


title: Porcine epidemic diarrhea virus infects and replicates in porcine alveolar macrophages

text: Abstract Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea; consequently, the small intestine was believed to be its only target organ. In this study, we found that PEDV infected not only the small intestines, but also the respiratory tract. Infection and replication of PEDV in the respiratory tract from naturally PEDV-infected piglets were examined by reverse transcription polymerase chain reaction, immunohistochemistry, and virus re-isolation. Our observations were confirmed by experimental inoculation, and we found that PEDV infection in the respiratory tract was specifically associated with alveolar macrophages in the lung. Vero cell-adapted PEDV was able to replicate in both primary alveolar macrophages and continuous porcine alveolar macrophage cells. Sequencing analysis of the spike (S) glycoprotein revealed that mutations in S might be a potential determinant of auxiliary targets for PEDV. The discovery that PEDV infects and replicates in alveolar macrophages provides new insights into its pathogenesis.


title: Prevention of Respiratory Disease in Cow/Calf Operations

text: Respiratory disease in nursing calves is a common, yet sporadic herd event. In herds that experience respiratory disease, this can be a frustrating experience. Beef cow operations have an expectation of losses during the calving season. Losses because of respiratory disease in calves, that are at least 1 month up to weaning age, is not a normal expectation. Veterinarians providing services and advice to these operations must be able to present scientific and logical recommendations to manage these events. A strong working knowledge of the risk factors contributing to clinical disease is necessary to developing prevention strategies.


Coronavirus Disease 2019 (COVID-19) and men’s reproductive health


title: Future impacts and trends in treatment of hospital wastewater

text: The world’s population growth and economic development result in the increased requirement of land, water, and energy. This increased demand leads to the deforestation, loss in biodiversity, imbalance in agriculture and food supply, climate change, and increase in food and travel trade, which result in emergence and reemergence of infectious diseases. This chapter discussed various emerging infectious diseases and their causative agents (Buruli ulcer and Bunyvirus). Furthermore, this chapter further illustrates the emergence of superbugs and the associated threat due to the presence of pharmaceutical compounds in the environment. The prevalence of pharmaceuticals in the environment exerts ecotoxic effects on living organisms and causes thousands of death every year. The threats associated with the pharmaceutical presence in the environment were briefly discussed in this chapter. Finally, this chapter provides the alternative methods to avoid the use of antibiotics and to develop novel treatment technologies (such as Phage therapy) to degrade and remove the pharmaceutical compounds.


title: Current Evidence for Minimally Invasive Surgery During the COVID-19 Pandemic and Risk Mitigation Strategies: A Narrative Review

text: Our objective was to review the literature surrounding the risks of viral transmission during laparoscopic surgery and propose mitigation measures to address these risks. SUMMARY BACKGROUND DATA: The SARS-CoV-2 pandemic has caused surgeons the world over to re-evaluate their approach to surgical procedures given concerns over the risk of aerosolization of viral particles and exposure of operating room staff to infection. International society guidelines advise against the use of laparoscopy; however, the evidence on this topic is scant and recommendations are based on the perceived most cautious course of action. METHODS: We conducted a narrative review of the existing literature surrounding the risks of viral transmission during laparoscopic surgery and balance these risks against the benefits of minimally invasive approaches. We also propose mitigation measures to address these risks that we have adopted in our institution. RESULTS AND CONCLUSION: While it is currently assumed that open surgery minimizes operating room staff exposure to the virus, our findings reveal that this may not be the case. A well-informed, evidence-based opinion is critical when making decisions regarding which operative approach to pursue, for the safety and well-being of the patient, the operating room staff, and the healthcare system at large. Minimally invasive surgical approaches offer significant advantages with respect to both patient care, and the mitigation of the risk of viral transmission during surgery, provided the appropriate equipment and expertise are present.


Bleeding in COVID-19 severe pneumonia: the other side of abnormal coagulation pattern?


title: Avian reovirus sigma C enhances the mucosal and systemic immune responses elicited by antigen-conjugated lactic acid bacteria

text: Abstract Mucosal surfaces are common sites of pathogen colonization/entry. Effective mucosal immunity by vaccination should provide protection at this primary infection site. Our aim was to develop a new vaccination strategy that elicits a mucosal immune response. A new strain of Enterococcus faecium, a non pathogenic lactic acid bacteria (LAB) with strong cell adhesion ability, was identified and used as a vaccine vector to deliver two model antigens. Specifically, sigma (σ) C protein of avian reovirus (ARV), a functional homolog of mammalian reovirus σ1 protein and responsible for M-cell targeting, was administered together with a subfragment of the spike protein of infectious bronchitis virus (IBV). Next, the effect of immunization route on the immune response was assessed by delivering the antigens via the LAB strain. Intranasal (IN) immunization induced stronger humoral responses than intragastic (IG) immunization. IN immunization produced antigen specific IgA both systemically and in the lungs. A higher IgA titer was induced by the LAB with ARV σC protein attached. Moreover, the serum of mice immunized with LAB displaying divalent antigens had much stronger immune reactivity against ARV σC protein compared to IBV-S1. Our results indicate that ARV σC protein delivered by LAB via the IN route elicits strong mucosal immunity. A needle-free delivery approach is a convenient and cost effective method of vaccine administration, especially for respiratory infections in economic animals. Furthermore, ARV σC, a strong immunogen of ARV, may be able to serve as an immunoenhancer for other vaccines, especially avian vaccines.


title: Surveillance to improve evidence for community control decisions during the COVID-19 pandemic – Opening the animal epidemic toolbox for public health

text: Abstract During the first few months of 2020, the COVID-19 pandemic has reached Europe. Health systems all over the world are trying to control the outbreak in the shortest possible time. Exotic disease outbreaks are not uncommon in animal health and randomised surveillance is frequently used as support for decision-making. This editorial discusses the possibilities of practicing One Health, by using methods from animal health to enhance surveillance for COVID-19 to provide an evidence base fort decision-making in communities and countries.


title: S-palmitoylation of swine interferon-inducible transmembrane protein is essential for its anti-JEV activity

text: Japanese encephalitis virus (JEV) is an infectious pathogen spreading in a wide range of vertebrate species. Pigs are amplifying hosts of JEV and thought to be maintained in nature predominantly by avian-mosquito cycles. In the innate immune system, interferon-inducible transmembrane protein (IFITM) is a small transmembrane protein family and has been identified as the first line of defense against a broad range of RNA virus invasion. In this paper, we found that swine IFITM (sIFITM) could restrict the replication of both JEV vaccine strain and wild strain NJ-2008. The cysteine S-palmitoylation modification of sIFITM plays important roles in their anti-JEV effects and intracellular distributions. Our findings show the anti-JEV activities of swine interferon-inducible transmembrane proteins and broaden the antiviral spectrum of IFITM protein family. The preliminary exploration of S-palmitoylation modification of sIFITM may contribute to understanding of the antiviral molecular mechanism of sIFITM.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) — Surveillance and testing in North England from 2012 to 2019

text: Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia in 2012 and caused an epidemic in the Middle East. Public Health England (PHE) Manchester is one of the two PHE centres in the UK that perform testing for MERS-CoV. The results of the PHE Manchester MERS surveillance from 2012 to 2019 are presented in this report. Methods Retrospective data were collected for returning travellers from the Middle East fitting the PHE MERS case definition. Respiratory samples were tested for respiratory viruses and MERS-CoV using an in-house RT-PCR assay. Results Four hundred and twenty-six (426) samples from 264 patients were tested for MERS Co-V and respiratory viruses. No MERS-CoV infections were identified by PCR. Fifty-six percent of samples were PCR positive for viral or bacterial pathogen with Influenza A as the predominant virus (44%). Sixty-two percent of all patients had a pathogen identified with the highest positivity from sputum samples. Patients with multiple samples demonstrated a 100% diagnostic yield. Conclusions Although no cases of MERS were identified, the majority of patients had Influenza infection for which oseltamivir treatment was indicated and isolation warranted. Sputum samples were the most useful in diagnosing respiratory viruses with a 100% diagnostic yield from patients with multiple samples.


title: Evaluation of the Temporal Association between Kawasaki Disease and Viral Infections in South Korea

text: BACKGROUND AND OBJECTIVES: This study is aimed at elucidating potential temporal associations between the occurrence of Kawasaki disease (KD) and various viral infections. SUBJECTS AND METHODS: We obtained monthly patterns of KD from the seventh nationwide survey and viral detection data from the Korea Centers for Disease Control and Prevention from 2009 to 2011 and evaluated temporal correlations between them for each month. The respiratory viruses detected using a multiplex real-time-polymerase chain reaction kit were influenza virus (A/H1N1, A/H3N2, A/H5N1, and B), adenovirus, parainfluenza virus (type 1, 2, 3), respiratory syncytial virus (type A, B), human rhinovirus, human coronavirus (OC43/229E, NL63), human bocavirus, and enterovirus. RESULTS: We obtained data from a total of 13031 patients who were treated for acute KD from 87 hospitals with pediatric residence programs. During this survey, KD showed highest overall incidence in summer and winter seasons and lowest incidence in February and October. We received viral detection data for a total of 14267 patients. Viral detection was highest during winter and spring seasons. The most commonly detected virus was human rhinovirus (32.6%), followed by influenza virus (26.8%). The monthly incidence of KD showed significant correlation with the monthly overall viral detection (p=0.022, r=0.382). In particular, human bocavirus and enterovirus have significant correlations with monthly patterns of KD occurrence (p=0.032 and p=0.007, respectively) and influenza virus correlated with KD occurrence with borderline significance (p=0.063). CONCLUSION: The temporal association between monthly occurrence of KD and viral detection suggests the etiologic importance of precedent infection in the development of KD.


docid: lsvdowvj

title: Pediatric Airway Management in Coronavirus Disease 2019 Patients: Consensus Guidelines From the Society for Pediatric Anesthesia’s Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society

text: The severe acute respiratory syndrome Coronavirus 2 (Coronavirus Disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.


title: Systemic infection of avian influenza A virus H5N1 subtype in humans

text: Summary The viral dissemination in a patient with avian influenza A subtype H5N1 infection was retrospectively studied by the immunohistochemical localization of viral nucleoprotein antigen. The pathology was marked by diffuse alveolar damage, lymphoid depletion, and reactive hemophagocytic syndrome. Besides the lung and the upper respiratory tract, viral antigen was detected in the small and large intestinal epithelial cells, hematopoietic cells in the bone marrow, glial cells and neurons of the brain, and lymphocytes. The results confirmed that H5N1 virus disseminated to multiple organs beyond the respiratory system. However, specific pathological changes were noted in the respiratory system only, and productive viral replication confirmed by culture was noted only in the lung. More postmortem studies are needed to elucidate the pathogenesis of this highly fatal zoonotic disease.


Comment on “Hearing loss and COVID-19: A note”


title: SEIR Modeling of the Italian Epidemic of SARS-CoV-2 Using Computational Swarm Intelligence

text: We applied a generalized SEIR epidemiological model to the recent SARS-CoV-2 outbreak in the world, with a focus on Italy and its Lombardy, Piedmont, and Veneto regions. We focused on the application of a stochastic approach in fitting the model parameters using a Particle Swarm Optimization (PSO) solver, to improve the reliability of predictions in the medium term (30 days). We analyzed the official data and the predicted evolution of the epidemic in the Italian regions, and we compared the results with the data and predictions of Spain and South Korea. We linked the model equations to the changes in people’s mobility, with reference to Google’s COVID-19 Community Mobility Reports. We discussed the effectiveness of policies taken by different regions and countries and how they have an impact on past and future infection scenarios.


title: Atypical erythema multiforme palmar plaques lesions due to Sars‐Cov‐2

text: Since CoronaVirus Disease 19 (COVID-19) was declared as a pandemic, all medical specialties were at the front, including dermatology. Daily, there are observations mentioning possible cutaneous manifestations of Sars-Cov-2. Among these manifestations, the most often was a rash which could be erythematous, morbilliform or urticarial mimicking viral exanthema, or chickenpox-like vesicles [1-3]. Anecdotally, dengue-like petechial eruption was reported [4].