title: Tarin, a Potential Immunomodulator and COX‐Inhibitor Lectin Found in Taro (Colocasia esculenta)

text: Taro (Colocasia esculenta) corm is a rustic staple food, rich in small starch granules, fibers, and bioactive phytoconstituents such as flavonoids, alkaloids, sterols, tannins, phytates, micronutrients, and proteins, including tarin, a GNA‐related lectin. Tarin exhibits recognized biocide activities against viruses and insects, has antitumoral properties and is an immunomodulator molecule candidate. It has been isolated in highly purified form (>90%) from taro corms through low‐cost and single‐step affinity chromatography. It comprises 2‐domain 27 to 28 kDa protomer, posttranslational cleaved into 2 nonidentical monomers, 11.9 and 12.6 kDa, held by noncovalent binding. At least 10 tarin isoforms sharing over 70% similarity have been described. The monomers assume the β‐prism II fold, consisting of 3 antiparallel β‐sheets formed by 4 β‐strands each. Tarin exhibits an expanded‐binding site for complex and high‐mannose N‐glycan chains 49, 212, 213, 358, 465, and 477 found on cell surface antigens of viruses, insects, cancer, and hematopoietic cells, explaining its broad biological activities. Tarin may stimulate innate and adaptive immune responses, enabling hosts to recover from infections or immunosuppressed status inherent to several pathological conditions. In a murine model, tarin stimulates the in vitro and in vivo proliferation of total spleen and bone marrow cells, especially B lymphocytes. Granulocyte repopulation has also been demonstrated in long‐term mice bone marrow cell cultures. As a potential immunomodulator, tarin, administered to immunosuppressed mice, attenuated cyclophosphamide‐induced leukopenia. We propose a molecular model that unites the potential prophylactic and therapeutic action of tarin on hematopoietic and cancer cells, as a potential immunomodulator.


title: Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy

text: Abstract The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.


title: Lineage replacement accompanying duplication and rapid fixation of an RNA element in the nsP3 gene in a species of alphavirus

text: Abstract A sequence of thirty-six nucleotides in the nsP3 gene of Ross River virus (RRV), coding for the amino acid sequence HADTVSLDSTVS, was duplicated some time between 1969 and 1979 coinciding with the appearance of a new lineage of this virus and with a major outbreak of Epidemic Polyarthritis among residents of the Pacific Islands. This lineage of RRV continues to circulate throughout Australia and both earlier lineages, which lacked the duplicated element, now are extinct. Multiple copies of several other elements also were observed in this region of the nsP3 gene in all lineages of RRV. Multiple copies of one of these, coding for the amino acid sequence P*P*PR, were detected in the C-terminal region of the nsP3 protein of all alphaviruses except those of African origin. The fixation of duplications and insertions in 3′ region of nsP3 genes from all lineages of alphaviruses, suggests they provide some fitness advantage.


title: Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

text: Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.


title: Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection

text: Abstract We report the sudden death of a 33-month-old child owing to acute respiratory distress syndrome due to human metapneumovirus (hMPV) infection. Of 30 children attending the same day care centre, 26% and 59% had hMPV and multiple infections, respectively; three of six children with pneumonia had a diagnosis of hMPV. hMPV infection is common in childhood viral co-infections but it can cause sudden death.


title: Intranasal Protollin-formulated recombinant SARS S-protein elicits respiratory and serum neutralizing antibodies and protection in mice

text: The feasibility of developing a prophylactic vaccine against SARS was assessed by comparing the immune responses elicited by immunizing mice with a recombinant SARS spike glycoprotein (S-protein) formulated with different adjuvants, given by different routes. In both young and aged mice, an intranasal Protollin-formulated S-protein vaccine elicited high levels of antigen-specific IgG in serum, comparable to those elicited by an intramuscular Alum-adsorbed S-protein vaccine. Serum antibodies were shown to be virus neutralizing. Intranasal immunization of young mice with the Protollin-formulated vaccine elicited significant levels of antigen-specific lung IgA in contrast to mice immunized with the intramuscular vaccine in which no antigen-specific lung IgA was detected. Following live virus challenge of aged mice, no virus was detected in the lungs of intranasally immunized mice, in contrast to intramuscularly immunized mice whose lung virus titers were comparable to those observed in control mice.


THORACIC SURGERY FOR MALIGNANCY AND EMERGENCY IRRESPECTIVE OF COVID-19


title: Impact of the COVID‐19 pandemic on therapeutic choices in thrombosis‐hemostasis

text: Major therapeutic developments have been achieved in the field of thrombotic and hemorrhagic diseases over the last decade. These include the development and validation of four direct oral anticoagulants (DOACs) indicated for numerous thrombotic disorders, both arterial and venous [1]. It also involves new haemostatic agents for hemophilia patients, in particular Factor VIII (FVIII) and Factor IX (FIX) concentrates with extended half-life (EHL) [2;3] and a bispecific antibody mimicking the action of FVIII (Emicizumab) [4;5].


Novel COronaVirus Disease 2019 (COVID-19) epidemic: What are the risk for systemic sclerosis patients?


title: Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014

text: BACKGROUND: Influenza typically comprises a substantial portion of acute respiratory infections, a leading cause of mortality worldwide. However, influenza epidemiology data are lacking in Egypt. We describe seven years of Egypt’s influenza hospitalizations from a multi-site influenza surveillance system. METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. Standardized demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, and influenza A specimens subtyped. RESULTS: From November 2007–November 2014, 2,936/17,441 (17%) SARI cases were influenza-positive. Influenza-positive patients were more likely to be older, female, pregnant, and have chronic condition(s) (all p<0.05). Among them, 53 (2%) died, and death was associated with older age, five or more days from symptom onset to hospitalization, chronic condition(s), and influenza A (all p<0.05). An annual seasonal influenza pattern occurred from July–June. Each season, the proportion of the season’s influenza-positive cases peaked during November–May (19–41%). CONCLUSIONS: In Egypt, influenza causes considerable morbidity and mortality and influenza SARI hospitalization patterns mirror those of the Northern Hemisphere. Additional assessment of influenza epidemiology in Egypt may better guide disease control activities and vaccine policy.


title: Peptides as Therapeutic Agents for Dengue Virus

text: Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.


ICAAC/ICC 2015


title: Surveillance of febrile patients in a district and evaluation of their spatiotemporal associations: a pilot study

text: BACKGROUND: Fever is an undifferentiated clinical feature that may enhance the sensitivity of syndromic surveillance systems. By studying the spatiotemporal associations of febrile patients, it may allow early detection of case clustering that indicates imminent threat of infectious disease outbreaks in the community. METHODS: We captured consecutive emergency department visits that led to hospitalization in a district hospital in Hong Kong during the period of 12 Sep 2005 to 14 Oct 2005. We recorded demographic data, provisional diagnoses, temperature on presentation and residential location for each patient-episode, and geocoded the residential addresses. We applied Geographical Information System technology to study the geographical distribution these cases, and their associations within a 50-m buffer zone spatially. A case cluster was defined by three or more spatially associated febrile patients within each three consecutive days. RESULTS: One thousand and sixty six patient-episodes were eligible for analysis; 42% of them had fever (>37°C; oral temperature) on presentation. Two hundred and four patient-episodes (19.1%) came from residential care homes for elderly (RCHE). We detected a total of 40 case clusters during the study period. Clustered cases were of older age; 57 (33.3%) were residents of RCHE. We found a median of 3 patients (range: 3 - 8) and time span of 3 days (range: 2 - 8 days) in each cluster. Twenty five clusters had 2 or more patients living in the same building block; 18 of them were from RCHE. CONCLUSIONS: It is technically feasible to perform surveillance on febrile patients and studying their spatiotemporal associations. The information is potentially useful for early detection of impending infectious disease threats.


title: Difference in sensitivity to interferon among mouse hepatitis viruses with high and low virulence for mice

text: Abstract Mouse hepatitis viruses (MHV) of different virulence for mice were studied with respect to interferon (IFN) sensitivity. The growth of low-virulent MHV-S and intermediately virulent MHV-JHM was significantly suppressed in IFN-treated L cells compared with untreated cells. However, a comparable suppression of the growth of highly virulent MHV-2 was not observed in IFN-treated cells. This differential effect of IFN treatment could also be demonstrated at the level of viral mRNA and viral proteins. In cells infected with MHV-S or MHV-JHM the amount of viral mRNAs was remarkably reduced by IFN treatment. Also the levels of the major intracellular viral proteins, in particular the E, protein, were affected by IFN treatment. Similar effects could not be demonstrated in MHV-2-infected cells. These results suggest that during MHV-S or MHV-JHM infection IFN treatment suppresses virus replication at several stages. The significance of these results is discussed in terms of the pathogenecity of these viruses.


title: The potential of memantine and related adamantanes such as amantadine, to reduce the neurotoxic effects of COVID‐19, including ARDS and to reduce viral replication through lysosomal effects

text: SARS-CoV-2 appears to have neurotropic aspects with neurotoxicity through interaction with ACE2 in the medullary brainstem, causing glutamate toxicity in the rostral ventrolateral medulla (RVLM), increased sympathetic tone, hypertension and pulmonary capillary leakage of fluid into the alveoli, resulting in acute respiratory distress syndrome (ARDS). Memantine, a moderate affinity, uncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist which prevents excess calcium entry into cells is commonly utilized in treating patients with Alzheimer's disease, and may inhibit the neurotoxicity induced by SARS-CoV-2 in the medullary brain stem to avoid development of ARDS. Memantine and related adamantine such as amantadine, which is utilized in Parkinson's disease and influenza, may have some anti-viral potential as well. Memantine and similar adamantines may have potential as repurposed medicines for treating Covid19 with inhibition of neurotoxicity, ARDS and viral replication, since Memantine appears to be lysosomotropic. This article is protected by copyright. All rights reserved.


title: Correction to: Responding to COVID-19: What’s the Problem?

text: Several types of resources coexist for coordinated action and systemic responses to this extraordinary situation--administrative, behavioural, financial, health care, legal and medical resources--that have been used at different geo-political levels, sometimes in an uncoordinated fashion of 'winner takes all'.


title: Viral Respiratory Infections in Hematological Patients

text: Viral infections of the respiratory system represent one of the most important complications in hematological patients in terms of both the severity of the clinical picture and its related impact on the duration of hospitalization, and of mortality. The most implicated viruses are those that commonly cause community-based respiratory diseases: respiratory syncytial virus, Influenza virus and rhinovirus. However, in some cases the clinical picture may be triggered by first infection with or reactivation of pathogens normally not responsible for clinically relevant diseases in immunocompetent subjects. This issue is currently being taken into greater consideration within the scientific community. However, the strong heterogeneity in the epidemiology and clinical expression of these infections and the lack of adequate therapeutic options imply that there is currently no uniform consensus on the best management of these patients. The main purpose of this review is to highlight which viruses are currently most implicated in the onset of these infections, what is their incidence in so heterogeneous and fragile patients and the factors that lead to disease's onset and evolution. Possible or available clinical management options, diagnostic and therapeutic tools, and preventive and prophylaxis measures are also discussed.


title: How long can nosocomial pathogens survive on textiles? A systematic review

text: Aims: Healthcare-associated infections linked to contaminated textiles are rare but underline their potential role as a source for transmission. The aim of the review was to summarize the experimental evidence on the survival and persistence of the different types of nosocomial pathogens on textiles. Methods: A literature search was performed on MedLine. Original data on the survival of bacteria, mycobacteria, and fungi and persistence of viruses on textiles were evaluated. Results: The survival of bacteria at room temperature was the longest on polyester (up to 206 days), whereas it was up to 90 days for some species on cotton and mixed fibers. Only low inocula of 100 CFU were found on all types of textiles with a short survival time of ≤3 days. Most bacterial species survived better at elevated air humidity. The infectivity of viruses on textiles is lost much faster at room temperature, typically within 2–4 weeks. Conclusions: Contaminated textiles or fabrics may be a source of transmission for weeks. The presence of pathogens on the coats of healthcare workers is associated with the presence of pathogens on their hands, demonstrating the relevance of textile contamination in patient care.


title: Rapid Molecular Panels: What Is in the Best Interest of the Patient? A Review of Patient Outcome Studies for Multiplex Panels Used in Bloodstream, Respiratory, and Neurological Infections

text: Abstract In the clinical microbiology laboratory, the focus when choosing new tests is often on performance, turnaround time, and labor needs. This review examines available rapid, multiplexed tests from a different perspective: that of the patient. It considers whether published evidence supports the notion that use of rapid, on-demand tests (as opposed to batched testing) leads to better patient outcomes and whether broad, syndrome-based, multiplexed panels translate into better patient care than narrower monoplex or duplex assays. Finally, we examine how synergy between the clinical microbiology and antimicrobial stewardship programs is necessary to ensure that rapid tests, if implemented, impact the patients they are designed to support.


88 Gender-Specific Issues in Non-HIV Viral Infections


title: Rapid detection and non-subjective characterisation of infectious bronchitis virus isolates using high-resolution melt curve analysis and a mathematical model

text: Infectious bronchitis virus (IBV) is a coronavirus that causes upper respiratory, renal and/or reproductive diseases with high morbidity in poultry. Classification of IBV is important for implementation of vaccination strategies to control the disease in commercial poultry. Currently, the lengthy process of sequence analysis of the IBV S1 gene is considered the gold standard for IBV strain identification, with a high nucleotide identity (e.g. ≥95%) indicating related strains. However, this gene has a high propensity to mutate and/or undergo recombination, and alone it may not be reliable for strain identification. A real-time polymerase chain reaction (RT-PCR) combined with high-resolution melt (HRM) curve analysis was developed based on the 3′UTR of IBV for rapid detection and classification of IBV from commercial poultry. HRM curves generated from 230 to 435-bp PCR products of several IBV strains were subjected to further analysis using a mathematical model also developed during this study. It was shown that a combination of HRM curve analysis and the mathematical model could reliably group 189 out of 190 comparisons of pairs of IBV strains in accordance with their 3′UTR and S1 gene identities. The newly developed RT-PCR/HRM curve analysis model could detect and rapidly identify novel and vaccine-related IBV strains, as confirmed by S1 gene and 3′UTR nucleotide sequences. This model is a rapid, reliable, accurate and non-subjective system for detection of IBVs in poultry flocks.


title: Private specificities of CD8 T cell responses control patterns of heterologous immunity

text: CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Rα by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.


title: High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays

text: BACKGROUND: Despite current knowledge of mutations in 45 genes that can cause nonsyndromic sensorineural hearing loss (SNHL), no unified clinical test has been developed that can comprehensively detect mutations in multiple genes. We therefore designed Affymetrix resequencing microarrays capable of resequencing 13 genes mutated in SNHL (GJB2, GJB6, CDH23, KCNE1, KCNQ1, MYO7A, OTOF, PDS, MYO6, SLC26A5, TMIE, TMPRSS3, USH1C). We present results from hearing loss arrays developed in two different research facilities and highlight some of the approaches we adopted to enhance the applicability of resequencing arrays in a clinical setting. RESULTS: We leveraged sequence and intensity pattern features responsible for diminished coverage and accuracy and developed a novel algorithm, sPROFILER, which resolved >80% of no-calls from GSEQ and allowed 99.6% (range: 99.2-99.8%) of sequence to be called, while maintaining overall accuracy at >99.8% based upon dideoxy sequencing comparison. CONCLUSIONS: Together, these findings provide insight into critical issues for disease-centered resequencing protocols suitable for clinical application and support the use of array-based resequencing technology as a valuable molecular diagnostic tool for pediatric SNHL and other genetic diseases with substantial genetic heterogeneity.


title: Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease

text: Abstract SARS coronavirus main protease (SARS-CoV Mpro) is essential for the replication of the virus and regarded as a major antiviral drug target. The enzyme is a cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site. Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV Mpro. Previous studies using peptidic substrates and inhibitors showed that the substrate specificity of SARS-CoV Mpro requires glutamine in the P1 position and a large hydrophobic residue in the P2 position. We determined four crystal structures of SARS-CoV Mpro in complex with pentapeptide aldehydes (Ac-ESTLQ-H, Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these aldehydes exhibit inhibitory activity towards SARS-CoV Mpro, with Ki values in the μM range. Surprisingly, the X-ray structures revealed that the hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid side-chains in the P2 positions of the inhibitors. Consequently, we reassessed the substrate specificity of the enzyme by testing the cleavage of 20 different tetradecapeptide substrates with varying amino-acid residues in the P2 position. The cleavage efficiency for the substrate with serine in the P2 position was 160-times lower than that for the original substrate (P2=Leu); furthermore, the substrate with aspartic acid in the P2 position was not cleaved at all. We also determined a crystal structure of SARS-CoV Mpro in complex with aldehyde Cm-FF-H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1 pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV Mpro, with Ki =2.24±0.58μM. These results show that the stringent substrate specificity of the SARS-CoV Mpro with respect to the P1 and P2 positions can be overruled by the highly electrophilic character of the aldehyde warhead, thereby constituting a deviation from the dogma that peptidic inhibitors need to correspond to the observed cleavage specificity of the target protease.


Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians (Version 1)


title: A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community

text: BACKGROUND: Gray wolves (Canis lupus) were reintroduced into Yellowstone National Park (YNP) after a >70 year absence, and as part of recovery efforts, the population has been closely monitored. In 1999 and 2005, pup survival was significantly reduced, suggestive of disease outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. We found high, constant exposure to canine parvovirus (wolf seroprevalence: 100%; coyote: 94%), canine adenovirus-1 (wolf pups [0.5–0.9 yr]: 91%, adults [≥1 yr]: 96%; coyote juveniles [0.5–1.5 yrs]: 18%, adults [≥1.6 yrs]: 83%), and canine herpesvirus (wolf: 87%; coyote juveniles: 23%, young adults [1.6–4.9 yrs]: 51%, old adults [≥5 yrs]: 87%) suggesting that these pathogens were enzootic within YNP wolves and coyotes. An average of 50% of wolves exhibited exposure to the protozoan parasite, Neospora caninum, although individuals’ odds of exposure tended to increase with age and was temporally variable. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. The years of high wolf-pup mortality in 1999 and 2005 in the northern region of the park were correlated with peaks in CDV seroprevalence, suggesting that CDV contributed to the observed mortality. CONCLUSIONS/SIGNIFICANCE: Of the pathogens we examined, none appear to jeopardize the long-term population of canids in YNP. However, CDV appears capable of causing short-term population declines. Additional information on how and where CDV is maintained and the frequency with which future epizootics might be expected might be useful for future management of the Northern Rocky Mountain wolf population.


title: Rewiring cellular networks by members of the Flaviviridae family

text: Members of the Flaviviridae virus family comprise a large group of enveloped viruses with a single-strand RNA genome of positive polarity. Several genera belong to this family, including the Hepacivirus genus, of which hepatitis C virus (HCV) is the prototype member, and the Flavivirus genus, which contains both dengue virus and Zika virus. Viruses of these genera differ in many respects, such as the mode of transmission or the course of infection, which is either predominantly persistent in the case of HCV or acutely self-limiting in the case of flaviviruses. Although the fundamental replication strategy of Flaviviridae members is similar, during the past few years, important differences have been discovered, including the way in which these viruses exploit cellular resources to facilitate viral propagation. These differences might be responsible, at least in part, for the various biological properties of these viruses, thus offering the possibility to learn from comparisons. In this Review, we discuss the current understanding of how Flaviviridae viruses manipulate and usurp cellular pathways in infected cells. Specifically, we focus on comparing strategies employed by flaviviruses with those employed by hepaciviruses, and we discuss the importance of these interactions in the context of viral replication and antiviral therapies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2017.170) contains supplementary material, which is available to authorized users.


title: Prevention by Design Construction and Renovation of Health Care Facilities for Patient Safety and Infection Prevention

text: The built environment supports the safe care of patients in health care facilities. Infection preventionists and health care epidemiologists have expertise in prevention and control of health care–associated infections (HAIs) and assist with designing and constructing facilities to prevent HAIs. However, design elements are often missing from initial concepts. In addition, there is a large body of evidence that implicates construction and renovation as being associated with clusters of HAIs, many of which are life threatening for select patient populations. This article summarizes known risks and prevention strategies within a framework for patient safety.


title: Molecular Mechanics of RNA Translocases

text: Historically, research on RNA helicase and translocation enzymes has seemed like a footnote to the extraordinary progress in studies on DNA-remodeling enzymes. However, during the past decade, the rising wave of activity in RNA science has engendered intense interest in the behaviors of specialized motor enzymes that remodel RNA molecules. Functional, mechanistic, and structural investigations of these RNA enzymes have begun to reveal the molecular basis for their key roles in RNA metabolism and signaling. In this chapter, we highlight the structural and mechanistic similarities among monomeric RNA translo-case enzymes, while emphasizing the many divergent characteristics that have caused this enzyme family to become one of the most important in metabolism and gene expression.


title: PTSD as the second tsunami of the SARS-Cov-2 pandemic

text: Since the first cases, the coronavirus disease (COVID-19) rapidly spread around the world, with hundred−thousand cases and thousands of deaths. Post-traumatic stress disorder (PTSD) is a common consequence of major disasters. Exceptional epidemic situations also promoted PTSD in the past. Considering that humanity is undergoing the most severe pandemic since Spanish Influenza, the actual pandemic of COVID-19 is very likely to promote PTSD. Moreover, COVID-19 was renamed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). With a poor understanding of viruses and spreading mechanisms, the evocation of SARS is generating a great anxiety contributing to promote PTSD. Quarantine of infected patients evolved to quarantine of ‘infected’ towns or popular districts, and then of entire countries. In the families of cases, the brutal death of family members involved a spread of fear and a loss of certainty, promoting PTSD. In the context of disaster medicine with a lack of human and technical resources, healthcare workers could also develop acute stress disorders, potentially degenerating into chronic PTSD. Globally, WHO estimates 30–50% of the population affected by a disaster suffered from diverse psychological distress. PTSD individuals are more at-risk of suicidal ideation, suicide attempt, and deaths by suicide – considering that healthcare workers are already at-risk occupations. We draw attention towards PTSD as a secondary effect of the SARS-Cov-2 pandemic, both for general population, patients, and healthcare workers. Healthcare policies need to take into account preventive strategy of PTSD, and the related risk of suicide, in forthcoming months.


title: Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan

text: Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world’s ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases.


title: Clinical evaluation of a multi-parameter customized respiratory TaqMan® array card compared to conventional methods in immunocompromised patients

text: Abstract Background Respiratory viral infections can cause significant morbidity and mortality in immunocompromised patients. Conventional tests routinely available at most institutions are limited by the number of detectable pathogens, by a poor sensitivity and/or a long turnaround time. Objectives To compare the performance of routine conventional testing with direct fluorescent antibody assays and viral culture to a customized TaqMan® array card (TAC) real-time PCR method, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. Study design We collected 143 respiratory samples from 120 symptomatic immunocompromised patients. Samples for which conventional and TAC results were discordant underwent further verification testing. Results The TAC assay identified viral pathogens in more samples than did conventional testing (77/143 versus 27/143; McNemar P <0.0001), even when TAC results for viruses that could not be detected by conventional testing were excluded from analysis (59/143 versus 26/143; P <0.0001). In addition, the TAC assay identified 18 samples with non-viral pathogens. Verification testing confirmed positive TAC results for 50 out of 55 samples for which conventional testing was negative. Two out of three samples with a positive conventional test but negative TAC result were confirmed positive. A viral and a total pathogen co-infection rate of 5.6% and 11.8% were found, respectively. Conclusions The customized TAC assay resulted in a significantly increased identification of respiratory viruses. This study provides a practical real-life assessment of the performance of the TAC assay in a population for whom rapid and accurate diagnosis of viral and atypical pathogens is crucial for appropriate clinical management.


title: PKR mediated regulation of inflammation and IL-10 during viral encephalomyelitis

text: Double-stranded RNA-dependent protein kinase (PKR) regulates antiviral activity, immune responses, apoptosis and neurotoxicity. Gliatropic coronavirus infection induced PKR activation in infected as well uninfected cells within the central nervous system (CNS). However, PKR deficiency only modestly increased viral replication and did not affect IFN-α/β or IL-1β expression. Despite reduced Il-6, Ccl5, and Cxcl10 mRNA, protein levels remained unaltered. Furthermore, PKR deficiency selectively reduced IL-10 production in CD4, but not CD8 T cells, without affecting CNS pathology. The results demonstrate the ability of PKR to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells.


title: Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings

text: Abstract Newcastle disease virus (NDV) and Goose parvovirus (GPV) are considered to be two of the most important and widespread viruses infecting geese. In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. Expression of the VP3 protein in rmNA-VP3 infected cells was detected by immunofluorescence and Western blot assay. The genetic stability was examined by serially passaging 10 times in 10-day-old embryonated SPF chicken eggs. Goslings were inoculated with rmNA-VP3 showed no apparent signs of disease and developed a strong GPV and NDV neutralizing antibodies response. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds.


title: The abatement of major pollutants in air and water by environmental catalysis

text: This review reports the research progress in the abatement of major pollutants in air and water by environmental catalysis. For air pollution control, the selective catalytic reduction of NO(x) (SCR) by ammonia and hydrocarbons on metal oxide and zeolite catalysts are reviewed and discussed, as is the removal of Hg from flue gas by catalysis. The oxidation of Volatile organic compounds (VOCs) by photo- and thermal-catalysis for indoor air quality improvement is reviewed. For wastewater treatment, the catalytic elimination of inorganic and organic pollutants in wastewater is presented. In addition, the mechanism for the procedure of abatement of air and water pollutants by catalysis is discussed in this review. Finally, a research orientation on environment catalysis for the treatment of air pollutants and wastewater is proposed.


title: Single-cell longitudinal analysis of SARS-CoV-2 infection in human bronchial epithelial cells

text: SARS-CoV-2, the causative agent of COVID-19, has resulted in more than 3,000,000 infections and 200,000 deaths. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2 we performed single-cell RNA sequencing of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface cultures over a time-course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as the major target of infection, which we confirmed by electron microscopy. Over the course of infection, cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell intrinsic expression of type I and type III IFNs and IL6 but not IL1. This results in expression of interferon stimulated genes in both infected and bystander cells. Here, we have conducted an in-depth analysis of SARS-CoV-2 infection in HBECs and provide a detailed characterization of genes, cell types, and cell state changes associated with the infection.


title: Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans

text: Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.


title: Guideline for Antibiotic Use in Adults with Community-acquired Pneumonia

text: Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea.


title: 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2

text: Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells’ survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.


title: Protective immunity and susceptibility to infectious diseases: lessons from the 1918 influenza pandemic

text: The influenza pandemic of 1918 killed nearly 50 million people worldwide and was characterized by an atypical W-shaped mortality curve, where adults between the ages of 30–60 years fared better than younger adults aged 18–30 years. In this review, we will discuss why this influenza virus strain was so virulent and how immunological memory to the 1918 virus may have shaped the W mortality curve. We will end on the topic of the 'honeymoon' period of infectious diseases—the clinically documented period between the ages of 4–13 years during which children demonstrate less morbidity and/or mortality to infectious diseases, in general, compared with young adults.


title: Rotavirus and concurrent infections with other enteropathogens in neonatal diarrheic dairy calves in Spain

text: Abstract Faeces samples from 218, one to 30 days old, diarrheic dairy calves in 65 dairy herds were screened for the presence of rotavirus and concurrent infections with coronavirus, Cryptosporidium, F5+ Escherichia coli and Salmonella spp. Calves were grouped according to their age as follows: 1–7, 8–14, 15–21 and 22–30 days. Rotavirus infection was detected in 46.9%, 45.6%, 33.8% and 48.3% of the calves in the respective age-groups. No significant differences in the detection rate of rotavirus were found among calves on the different age-groups. Rotavirus was the only enteropathogen detected in 39 of the 93 (41.9%) diarrheic calves positive to this agent. Concurrent infections with other enteropathogen(s) were detected in 31.3%, 33.3%, 20.6% and 3.4% of the rotavirus infected calves in the age-groups 1–7, 8–14, 15–21 and 22–30 d, respectively. A significant age-associated decrease in the detection rate of mixed infections (p<0.01) was found. The detection rates of the other enteropathogens considered in calves with rotavirus infection were 20.4% for coronavirus, 85.2% for Cryptosporidium, 16.7% for F5+ E. coli and 1.8% for Salmonella.


title: Achievement V – Methods for breaking the transmission of pathogens along the food chain Detection of viruses in food

text: Traditionally the focus for control of food-borne disease has been bacteria. During the last decade viruses have emerged as important sources of food borne human disease. Since the traditional bacteriological indicators, are not reliable for viral contamination, new methods are needed. PCR has enhanced the detection of virus in food. A challenge for developing detection reliable methods for viruses in food is that food matrices vary in composition, high sequence variability and inhibitors may be present. Therefore it is necessary to develop assays that have high diagnostic sensitivity, are broad and robust, and combine sample concentration and removal of inhibitors.


title: Impact of the COVID‐19 pandemic on interventional cardiology fellowship training in the New York metropolitan area: A perspective from the United States epicenter

text: BACKGROUND: The healthcare burden posed by the coronavirus disease 2019 (COVID‐19) pandemic in the New York Metropolitan area has necessitated the postponement of elective procedures resulting in a marked reduction in cardiac catheterization laboratory (CCL) volumes with a potential to impact interventional cardiology (IC) fellowship training. METHODS: We conducted a web‐based survey sent electronically to 21 Accreditation Council for Graduate Medical Education accredited IC fellowship program directors (PDs) and their respective fellows. RESULTS: Fourteen programs (67%) responded to the survey and all acknowledged a significant decrease in CCL procedural volumes. More than half of the PDs reported part of their CCL being converted to inpatient units and IC fellows being redeployed to COVID‐19 related duties. More than two‐thirds of PDs believed that the COVID‐19 pandemic would have a moderate (57%) or severe (14%) adverse impact on IC fellowship training, and 21% of the PDs expected their current fellows' average percutaneous coronary intervention (PCI) volume to be below 250. Of 25 IC fellow respondents, 95% expressed concern that the pandemic would have a moderate (72%) or severe (24%) adverse impact on their fellowship training, and nearly one‐fourth of fellows reported performing fewer than 250 PCIs as of March 1st. Finally, roughly one‐third of PDs and IC fellows felt that there should be consideration of an extension of fellowship training or a period of early career mentorship after fellowship. CONCLUSIONS: The COVID‐19 pandemic has caused a significant reduction in CCL procedural volumes that is impacting IC fellowship training in the NY metropolitan area. These results should inform professional societies and accreditation bodies to offer tailored opportunities for remediation of affected trainees.


title: Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus

text: BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004 ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children


New Hepatitis E Virus Genotype in Bactrian Camels, Xinjiang, China, 2013


title: Analogies Between Cancer-Derived Extracellular Vesicles and Enveloped Viruses with an Emphasis on Human Breast Cancer

text: PURPOSE OF REVIEW: Cancer cells utilize extracellular vesicles (EVs) as a means of transferring oncogenic proteins and nucleic acids to other cells to enhance the growth and spread of the tumor. There is an unexpected amount of similarities between these small, membrane-bound particles and enveloped virions, including protein content, physical characteristics (i.e., size and morphology), and mechanisms of entry and exit into target cells. RECENT FINDINGS: This review describes the attributes shared by both cancer-derived EVs, with an emphasis on breast cancer-derived EVs, and enveloped viral particles and discusses the methods by which virions can utilize the EV pathway as a means of transferring viral material and oncogenes to host cells. Additionally, the possible links between human papilloma virus and its influence on the miRNA content of breast cancer-derived EVs are examined. SUMMARY: The rapidly growing field of EVs is allowing investigators from different disciplines to enter uncharted territory. The study of the emerging similarities between cancer-derived EVs and enveloped virions may lead to novel important scientific discoveries.


title: Silver as a Disinfectant

text: The antimicrobial effects of silver (Ag) have been recognized for thousands of years. In ancient times, it was used in water containers (Grier 1983) and to prevent putrefaction of liquids and foods. In ancient times in Mexico, water and milk were kept in silver containers (Davis and Etris 1997). Silver was also mentioned in the Roman pharmacopoeia of 69 b.c. (Davis and Etris 1997).


Superficial thrombophlebitis in a patient with COVID 19: Heparin treatment after evaluation of D ‐ Dimer: COVID 19 and Superficial thrombophlebitis


Striking a balance between principle and pragmatism in COVID-19-related enforcement in Hong Kong


title: Renin-Angiotensin System Inhibition in Cardiovascular Patients at the Time of COVID19: Much Ado for Nothing? A Statement of Activity from the Directors of the Board and the Scientific Directors of the Italian Society of Hypertension

text: Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin–Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms are actually occurring in the present COVID-19 outbreak. Here we present the reasoned statement of the Italian Society of Hypertension to maintain ongoing antihypertensive treatments. Furthermore, the Italian Society of Hypertension presents its own initiative to investigate the issue using an online questionnaire to collect relevant data in human disease.


title: The scientific literature on Coronaviruses, COVID-19 and its associated safety-related research dimensions: A scientometric analysis and scoping review

text: Abstract The COVID-19 global pandemic has generated an abundance of research quickly following the outbreak. Within only a few months, more than a thousand studies on this topic have already appeared in the scientific literature. In this short review, we analyse the bibliometric aspects of these studies on a macro level, as well as those addressing Coronaviruses in general. Furthermore, through a scoping analysis of the literature on COVID-19, we identify the main safety-related dimensions that these studies have thus far addressed. Our findings show that across various research domains, and apart from the medical and clinical aspects such as the safety of vaccines and treatments, issues related to patient transport safety, occupational safety of healthcare professionals, biosafety of laboratories and facilities, social safety, food safety, and particularly mental/psychological health and domestic safety have thus far attracted most attention of the scientific community in relation to the COVID-19 pandemic. Our analysis also uncovers various potentially significant safety problems caused by this global health emergency which currently have attracted only limited scientific focus but may warrant more attention. These include matters such as cyber safety, economic safety, and supply-chain safety. These findings highlight why, from an academic research perspective, a holistic interdisciplinary approach and a collective scientific effort is required to help understand and mitigate the various safety impacts of this crisis whose implications reach far beyond the bio-medical risks. Such holistic safety-scientific understanding of the COVID-19 crisis can furthermore be instrumental to be better prepared for a future pandemic.


title: Die „historische Studie“ SOLIDARITY als Antwort der Forschung auf die Sars-CoV-2 Pandemie

text: This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. The novel coronavirus (Sars-CoV-2) poses a huge challenge to the world community. Knowledge about the virus and its properties is limited, but there is a great need to base political and medical decisions on scientific knowledge. This situation is leading to a dynamization of research. A prominent example of such a development is SOLIDARITY. The epistemological dimensions of this trial, which is coordinated by the WHO, and the resulting ethical implications are discussed in this article.


title: Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone

text: Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.


title: Extensive genetic diversity of bat-borne polyomaviruses reveals inter-family host-switching events

text: Polyomaviruses (PyVs) are small, double-stranded DNA tumor viruses carried by diverse vertebrates. PyVs have previously been considered highly host restricted in mammalian hosts, with host-switching events thought rare or nonexistent. Prior investigations have revealed short-range host-switching events of PyVs in two different African bat species within the horseshoe bat genus Rhinolophus. Herein, we have conducted a systematic investigation of PyVs in 1,083 archived bat samples collected from five provinces across China, and identified 192 PyVs from 186 bats from 15 host species within 6 families (Rhinolophidae, Vespertilionidae, Hipposideridae, Emballonuridae, Miniopteridae and Pteropodidae) representing 28 newly-described PyVs, indicative of extensive genetic diversity of bat PyVs. Surprisingly, two PyVs were identified in multiple bat species from different families, and another PyV clustered phylogenetically with PyVs carried by bats from a different host family, indicative of three inter-family PyV host-switching events. The time to most recent common ancestor (tMRCA) of the three events was estimated at 0.02-11.6 million years ago (MYA), which is inconsistent with the estimated tMRCA of their respective bat hosts (36.3-66.7 MYA), and is most parsimoniously explained by host-switching events. PyVs identified from geographically separated Chinese horseshoe bat species in the present study showed close genetic identities, and clustered with each other and with PyVs from African horseshoe bats, allowing assessment of the effects of positive selection in VP1 within the horseshoe bat family Rhinolophidae. Correlation analysis indicated that co-evolution with their hosts contributed much more to evolutionary divergence of PyV than geographic distance. In conclusion, our findings provide the first evidence of inter-family host-switching events of PyV in mammals and challenge the prevailing evolutionary paradigm for strict host restriction of mammalian PyVs. Since the discovery of murine polyomavirus in the 1950s, polyomaviruses (PyVs) have been considered both genetically stable and highly host-restricted in their mammalian hosts. In this study, we have identified multiple cases of host-switching events of PyVs by large scale surveillance in diverse bat species collected in China. These host-switching events occurred between bat families living in the same colony, indicating that a large population with frequent contacts between different bat species may represent an ecological niche facilitating PyV host-switching. The cases studied involved members of bats from several families, including horseshoe bats, which were previously found to harbor a number of highly virulent viruses to both humans and domestic animals. Our findings have provided evidence that even highly host-specific DNA viruses can transmit between bats of different species and indicate an increased propensity for spillover events involving horseshoe bats. We propose an evolutionary scheme for bat-borne PyVs in which intra-host divergence and host-switching has generated the diverse PyVs in present day bats. This scheme provides a useful model to study the evolution of PyVs in other hosts and, potentially, the modeling of bat zoonoses and the transmission of other DNA viruses in other mammals, including humans.


title: Le franchissement de la barrière inter-espèces : dernier obstacle avant la pandémie

text: Résumé Nombre de maladies émergentes récentes (Sida, Sras, grippe aviaire) ont en commun d’être des zoonoses liées à des virus ayant franchi la barrière inter-espèces. L’amélioration des systèmes de surveillance épidémiologique permet de suivre en temps réel la progression des nouvelles épidémies, tandis que les outils de biologie moléculaire modernes permettent de mieux comprendre les étapes nécessaires à l’adaptation du virus à son nouvel hôte. La mise en commun de ces observations met en évidence une transmissibilité moindre des souches virales en début d’épidémie. Il est donc primordial de renforcer les systèmes de surveillance épidémiologique, afin d’agir tôt et fort sur des épidémies débutantes, avant que le virus ne se soit adapté à l’homme. Les mesures de contrôle mises en place précocement en seront d’autant plus efficaces. Abstract Many emerging diseases (AIDS, SARS, avian flu) are related to viral zoonoses, which have crossed the interspecies barrier. The improvement of epidemiological surveillance has allowed live monitoring of epidemic progresses, while new molecular biological tools have allowed analysis of the various steps required for viral adaptation to their new hosts. These observations suggest lower transmissibility of viral strains at the start of epidemics. It is therefore essential to strengthen public health surveillance systems, so that swift moves can be made before viruses get adapted to humans. Early control measures will be more efficient.


title: Salvage use of tissue plasminogen activator (tPA) in the setting of acute respiratory distress syndrome (ARDS) due to COVID-19 in the USA: a Markov decision analysis

text: BACKGROUND: COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO(2)/FiO(2) (mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic. METHODS: A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO(2)/FiO(2) of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature. RESULTS: The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios. CONCLUSIONS: Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.


title: Interactions between business conditions and financial performance of tourism firms: Evidence from China and Taiwan

text: This study contributes to the fields of hospitality and tourism by examining interactions between business conditions and financial performance of tourism firms in both China and Taiwan. We investigate whether the improvement of business conditions enhances financial performance of tourism firms and whether financial success of tourism firms matters to business development. In general, cointegration test results support a long-run equilibrium relationship between the two variables, business conditions and financial performance of tourism firms, and Granger causality test results show that these two factors reinforce each other in both China and Taiwan. This study therefore documents significant contributions of financial success of tourism firms to business development and strengthening of financial performance of tourism firms by business conditions. Some managerial implications are also discussed.


title: Molecular Survey for Selected Viral Pathogens in Wild Leopard Cats (Prionailurus bengalensis) in Taiwan with an Emphasis on the Spatial and Temporal Dynamics of Carnivore Protoparvovirus 1

text: The leopard cat (Prionailurus bengalensis) has been listed as an endangered species under the Wildlife Conservation Act in Taiwan since 2009. In this study, we targeted viral pathogens, included carnivore protoparvovirus 1 (CPPV-1), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), coronavirus (CoV), and canine morbillivirus (CMV), using molecular screening. The spatial and temporal dynamics of the target pathogens were evaluated. Through sequencing and phylogenetic analysis, we aimed to clarify the phylogenetic relationship of isolated viral pathogens between leopard cats and domestic carnivores. Samples from 23 and 29 leopard cats that were live-trapped and found dead, respectively, were collected from Miaoli County from 2015 to 2019 in northwestern Taiwan. CPPV-1 and coronavirus were detected in leopard cats. The prevalence (95% confidence interval) of CPPV-1, and CoV was 63.5% (50.4%–76.6%) and 8.8% (0%–18.4%), respectively. The majority of sequences of each CPPV-1 strain amplified from Taiwanese leopard cats and domestic carnivores were identical. All the amplified CoV sequences from leopard cats were identified as feline coronavirus. The spatial and temporal aggregation of CPPV-1 infection in leopard cats was not determined in the sampling area, which indicated a wide distribution of CPPV-1 in the leopard cat habitat. We consider sympatric domestic carnivores to be the probable primary reservoir for the pathogens identified. We strongly recommend establishing efforts to manage CPPV-1 and FCoV in the leopard cat habitat, with an emphasis on vaccination programs and population control measures for free-roaming dogs and cats. IMPORTANCE The leopard cat (Prionailurus bengalensis) is an endangered species in Taiwan. The effects of infectious diseases on the wildlife population have increasingly been recognized. In this study, we targeted highly pathogenic viral pathogens in wild cat species, included carnivore protoparvovirus 1 (CPPV-1), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), coronavirus (CoV), and canine morbillivirus (CMV), using molecular screening. Furthermore, we collected the epidemiological and phylogenetic data to understand the spatial and temporal dynamics of the target pathogens in the wild leopard cat population and identified the possible origin of target pathogens. Based on our study, we consider sympatric domestic carnivores to be the probable primary reservoir for the pathogens identified. Our study provides a deeper understanding related to the distribution of target viral pathogens in the wild leopard cats. The information is essential for leopard cat conservation and pathogen management.


title: A novel inline PEEP valve design for differential multi-ventilation

text: BACKGROUND: Ventilator sharing is one option to emergently increase ventilator capacity during a crisis but has been criticized for its inability to adjust for individual patient needs. Newer ventilator sharing designs use valves and restrictors to control pressures for each patient. A key component of these designs is an inline Positive End Expiratory Pressure (PEEP) Valve but these are not readily available. Creating an inline PEEP valve by converting a standard bag-valve-mask PEEP valve is possible with the addition of a 3D printer collar. METHODS: This was a feasibility study assessing the performance and safety of a method for converting a standard PEEP valve into an inline PEEP valve. A collar was designed and printed that covers the exhaust ports of the valve and returns exhaled gases to the ventilator. RESULTS: The collar piece was simple to print and easily assembled with the standard PEEP valve. In bench testing it successfully created differential pressures in 2 simulated expiratory limbs without leaking to the atmosphere at pressures greater than 60 cm of H2O. CONCLUSION: Our novel inline PEEP valve design shows promise as an option for building a safer ventilator sharing system.


title: Assessing the interactions between COVID-19 and influenza in the United States

text: The 2019–2020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019–2020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019–2020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019–2020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal.


title: Effects of an Omega-3 and Vitamin D Supplement on Fatty Acids and Vitamin D Serum Levels in Double-Blinded, Randomized, Controlled Trials in Healthy and Crohn’s Disease Populations

text: Two trials separately measured the bioavailability and impact on inflammation of a supplement taken daily containing 510 mg Docosahexaenoic acid (DHA), 344 mg Eicosapentaenoic acid (EPA), and 1000 IU of vitamin D (25-hydroxyvitamin D; 25(OH)D), for healthy and Crohn’s disease (CD) populations. Both trials were double blinded, randomized, placebo-controlled with cross-over. Participants were randomly allocated to groups A (placebo then supplement) or B (supplement then placebo). Both included a washout. Fatty acid (N-3 PUFAs) and vitamin D serum levels, plasma C-reactive protein (CRP), and stool calprotectin were measured before and after each treatment period. Outcome measures were analyzed using generalized linear mixed models, including terms for treatment, period, and a treatment-by-period interaction. The supplement significantly increased serum levels in healthy and CD groups for EPA (p < 0.001 and p < 0.001, respectively), Docosapentaenoic acid (p < 0.001 and 0.005), DHA (p < 0.001 and 0.006), the omega-3 index (p < 0.001 and 0.001), and (vitamin D (p < 0.001 and 0.027). CRP and calprotectin measures showed no evidence of a treatment effect on inflammation; however, model estimation was imprecise for both outcomes, hence further research is required to elucidate potential inflammation effects. The nutrient supplement increased serum levels of key N-3 PUFAs and vitamin D in both populations, showing the preparation was readily bioavailable.


title: Modifications in the branched arms of a class of dual inhibitors of HIV and EV71 replication expand their antiviral spectrum

text: Abstract We have previously reported a new class of dendrimers with tryptophan (Trp) residues on the surface that show dual antiviral activities against HIV and enterovirus EV71. The prototype compound of this family is a derivative of pentaerythritol with 12 peripheral Trp groups and trivalent spacer arms. Here a novel series of dendrimers with divalent and tetravalent branched arms, instead of the trivalent ones present on the prototype, has been synthesized and its activity against HIV, EV71 and a panel of 16 different viruses and other pathogens has been determined. Convergent or divergent approaches have been used for the synthesis of these compounds. Our findings demonstrate that only compounds with tetravalent branched arms showed the same anti-HIV and anti-EV71 activity of the prototype (low micromolar) and even gain significant antiviral activity against new pathogens such as HSV-2, adenovirus-2, human corona virus and respiratory syncytial virus, being the first members of the Trp dendrimer family that showed activity against those viruses. As the prototype, these compounds also showed low-nanomolar activity against a representative EV71 clinical isolate. Experimental work carried on to determine the mode of action of the most potent IIa, containing tetravalent branched arms, demonstrated that it interacts with the viral envelopes of HIV, EV71 and HSV-2 and thus may prevent virus attachment to the host cell. These results support the interest of this new series of Trp dendrimers and qualify them as useful prototypes for the development of novel inhibitors of viral entry with broad antiviral spectrum.


title: Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China

text: Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.


title: The Epidemiology of COVID-19 cases and the Successful Containment Strategy in Hong Kong – January to May 2020

text: BACKGROUND: Hong Kong, a Special Administrative Region of China, recorded its first confirmed Coronavirus disease 2019 (COVID-19) case on 23 January 2020. We reviewed the case epidemiology and the various public health measures implemented from January to May 2020. METHOD: We described and compared the epidemiological and clinical characteristics of the cases recorded in different phases of the epidemic and reviewed the effectiveness of the public health measures implemented using the changes in the daily number of confirmed cases and the interval from symptom onset to hospital admission. RESULTS: Between January and May 2020, 1084 confirmed COVID-19 cases were reported, about 70% of which had travel history during the incubation period. The case fatality ratio was 0.4%. The local epidemic progressed through four phases: (i) preparedness and imported infection from mainland China, (ii) local transmission, (iii) imported infection from overseas countries associated with local transmission, and (iv) controlled imported infection with limited local transmission, with an eventual reduction of daily case number and minimization of onset-to-admission interval. Various public health measures, including enhanced surveillance, border control and social distancing, were introduced in phases in response to the prevailing local and global situations. DISCUSSION: Hong Kong’s overall containment strategy has led to a stabilization of number of cases and absence of community-wide outbreak in the 4.5 months since the reporting of the first case. Hong Kong’s strategy of containment might serve as an example for future planning of preparedness and response against novel infectious agents.


title: Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro

text: Abstract This report describes the application of real-time PCR for testing antivirals against highly pathogenic viruses such as Lassa virus, SARS coronavirus and Ebola virus. The test combines classical cell culture with a quantitative real-time PCR read-out. The assay for Lassa virus was validated with ribavirin, which showed an IC50 of 9μg/ml. Small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against Lassa virus. The analogues contained either dinitrile or diester groups at the imidazole 4,5-positions, and many of which possessed an acyclic sugar or sugar phosphonate moiety at the imidazole 1-position. The IC50 values of the most active compounds ranged from 5 to 21μg/ml. The compounds also inhibited replication of SARS coronavirus and Ebola virus in analogous assays, although to a lesser extent than Lassa virus.


title: Host‐cell lipid rafts: a safe door for micro‐organisms?

text: The lipid raft hypothesis proposed that these microdomains are small (10–200 nM), highly dynamic and enriched in cholesterol, glycosphingolipids and signalling phospholipids, which compartmentalize cellular processes. These membrane regions play crucial roles in signal transduction, phagocytosis and secretion, as well as pathogen adhesion/interaction. Throughout evolution, many pathogens have developed mechanisms to escape from the host immune system, some of which are based on the host membrane microdomain machinery. Thus lipid rafts might be exploited by pathogens as signalling and entry platforms. In this review, we summarize the role of lipid rafts as players in the overall invasion process used by different pathogens to escape from the host immune system.


Human Angiotensin - Converting Enzyme 2 (ACE2) is a Receptor for Human Respiratory Coronavirus NL63


title: Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence

text: Abstract The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no “specific drug” available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, “conventional drug in new use” becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the “specific drug”. China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.


Teaching nuclear medicine in the pandemic—a new challenge for the faculty


title: Pandemic COVID-19 Joins History’s Pandemic Legion

text: With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history. Some have killed sizeable percentages of humanity, but humans have always searched for, and often found, ways of mitigating their deadly effects. We here review the ancient and modern histories of such diseases, discuss factors associated with their emergences, and attempt to identify lessons that will help us meet the current challenge.


title: Observational Cohort Study of Oral Mycobiome and Interkingdom Interactions over the Course of Induction Therapy for Leukemia

text: Although the term “microbiome” refers to all microorganisms, the majority of microbiome studies focus on the bacteriome. Here, we characterize the oral mycobiome, including mycobiome-bacteriome interactions, in the setting of remission-induction chemotherapy (RIC) for acute myeloid leukemia (AML). Oral samples (n = 299) were prospectively collected twice weekly from 39 AML patients during RIC until neutrophil recovery. Illumina MiSeq 16S rRNA gene (V4) and internal transcribed spacer 2 (ITS2) sequencing were used to determine bacterial and fungal diversity and community composition. Intrakingdom and interkingdom network connectivity at baseline (T1) and at midpoint (T3) and a later time point (T6) were assessed via SPIEC-EASI (sparse inverse covariance estimation for ecological association inference). In this exploratory study, mycobiome α-diversity was not significantly associated with antibiotic or antifungal receipt. However, postchemotherapy mycobiome α-diversity was lower in subjects receiving high-intensity chemotherapy. Additionally, greater decreases in Malassezia levels were seen over time among patients on high-intensity RIC compared to low-intensity RIC (P = 0.003). A significantly higher relative abundance of Candida was found among patients who had infection (P = 0.008), while a significantly higher relative abundance of Fusarium was found among patients who did not get an infection (P = 0.03). Analyses of intrakingdom and interkingdom relationships at T1, T3, and T6 indicated that interkingdom connectivity increased over the course of IC as bacterial α-diversity diminished. In (to our knowledge) the first longitudinal mycobiome study performed during AML RIC, we found that mycobiome-bacteriome interactions are highly dynamic. Our study data suggest that inclusion of mycobiome analysis in the design of microbiome studies may be necessary to optimally understand the ecological and functional role of microbial communities in clinical outcomes. IMPORTANCE This report highlights the importance of longitudinal, parallel characterization of oral fungi and bacteria in order to better elucidate the dynamic changes in microbial community structure and interkingdom functional interactions during the injury of chemotherapy and antibiotic exposure as well as the clinical consequences of these interrelated alterations.


Editorial JTH 16 –The Coronavirus Disease COVID-19 and implications for transport and health


Pandemic, panic, and psychiatrists - what should be done before, during, and after COVID-19?


title: Virus et auto-immunité

text: Les virus sont depuis longtemps associés aux maladies auto-immunes. Plusieurs mécanismes ont été proposés pour expliquer comment une infection virale peut annuler la tolérance immunitaire et initier un processus autoréactif spécifique d'organe. Nous discutons deux mécanismes potentiels d'initiation virale de l'autoimmunité, le mimétisme moléculaire et l'inflammation locale accompagnée d'activation. Ils jouent un rôle central dans le développement de l'auto-immunité et ne sont pas mutuellement exclusifs, ce qui leur permet une contribution individuelle à la maladie. Des arguments récents suggèrent un rôle supplémentaire des virus dans la réactivation et la chronicité des maladies auto-immunes.


The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012–2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012–2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections.


title: Clinical Evaluation of Rodents

text: Small rodents are gaining popularity as pets and more owners are seeking veterinary care for these animals. Although there is a wealth of information available on this species, it is often disseminated among a large variety of texts and journals, thereby making access difficult for the veterinary practitioner. This article is designed to provide introductory information for the clinician performing a basic physical examination. Differential diagnoses for common clinical signs are discussed.


title: Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α

text: Current treatment schemes for severe acute respiratory syndrome (SARS) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. Ribavirin did not inhibit viral growth at concentrations attainable in human serum. In contrast, IFN-α showed an in vitro inhibitory effect starting at concentrations of 1000 IU/mL. In conclusion, ribavirin alone is unlikely to be beneficial in the prophylaxis or treatment of SARS CoV infections. Clinical trials with IFN-α might be justified to determine a beneficial effect on the outcome of SARS.


title: SARS Knowledge, Perceptions, and Behaviors: a Comparison between Finns and the Dutch during the SARS Outbreak in 2003

text: BACKGROUND: The SARS outbreak served to test both local and international outbreak management and risk communication practices. PURPOSE: The study compares SARS knowledge, perceptions, behaviors, and information between Finns and the Dutch during the SARS outbreak in 2003. METHOD: The participants of the study, who used a modified SARS Psychosocial Research Consortium survey, were drawn from Internet panels in Finland (n = 308) and the Netherlands (n = 373) in June 2003. Multiple logistic regression analyses were used to calculate odds ratios (with 95% confidence intervals) to compare Finns with the Dutch for various levels of perceptions and behaviors. RESULTS: Adjusted for age, education, and income, Finns were more likely to be knowledgeable and worried about SARS as well as to have low perceived comparative SARS risk and poor personal efficacy beliefs about preventing SARS. Finns were also more likely than the Dutch to have high confidence in physicians on SARS issues but less likely to have received information from the Internet and have confidence in Internet information. CONCLUSIONS: The study shed light on how two European populations differed substantially regarding lay responses to SARS. Understanding these differences is needed in formulating and executing communication and outbreak management.


title: Oral administration of Lactococcus lactis expressing Helicobacter pylori Cag7-ct383 protein induces systemic anti-Cag7 immune response in mice

text: To express the 3′-region (1152 bp) of the cag7 gene of Helicobacter pylori 51 strain, encoding the C-terminal 383 amino acid (ct383 aa) region of Cag7 protein that is known to cover the needle region of T4SS, in a live delivery vehicle Lactococcus lactis, the cag7-ct383 gene was amplified by PCR. DNA sequence analysis revealed that the amino acid sequence of Cag7-ct383 of H. pylori 51 shared 98.4% and 97.4% identity with H. pylori 26695 and J99, respectively. Intramuscular injection of the GST-Cag7-ct383 fusion protein into a rat could raise the anti-Cag7 antibody, indicating the immunogenicity of the Cag7-ct383 protein. When the cag7-ct383 gene was cloned in Escherichia coli–L. lactis shuttle vector (pMG36e) and transformed into L. lactis, the transformant could produce the Cag7-ct383 protein, as evidenced by Western blot analysis. The Cag7-ct383 protein level in the L. lactis transformant reached a maximum at the early stationary phase without extracellular secretion. The oral administration of the L. lactis transformant into mice generated anti-Cag7 antibody in serum in five of five mice. These results suggest that L. lactis transformant expressing Cag7-ct383 protein may be applicable as an oral vaccine to induce mucosal and systemic immunity to H. pylori.


title: An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles

text: Abstract In this paper, an improved recovery method for target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs) is reported. This method takes advantages of the amino-modified silica-coated magnetic nanoparticles prepared using water-in-oil microemulsion technique, which employs amino-modified silica as the shell and iron oxide as the core of the magnetic nanoparticles. The nanoparticles have a silica surface with amino groups and can be conjugated with any desired bio-molecules through many existing amino group chemistry. In this research, a linear DNA probe was immobilized onto nanoparticles through streptavidin conjugation using covalent bonds. A target ssDNA(I) (5′-TMR-CGCATAGGGCCTCGTGATAC-3′) has been successfully recovered from a crude sample under a magnet field through their special recognition and hybridization. A designed ssDNA fragment of severe acute respiratory syndrome (SARS) virus at a much lower concentration than the target ssDNA(I) was also recovered with high efficiency and good selectivity.


title: Human Airway Epithelial Cell Cultures for Modeling Respiratory Syncytial Virus Infection

text: Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.


title: Cutaneous signs in COVID‐19 patients: A review

text: Coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID‐19. We will focus on such disorders that are caused by direct action of SARS‐CoV‐2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug‐induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID‐19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID‐19 may help in early diagnosis, triage of patients, and risk stratification.


title: Spectroscopy with computational analysis in virological studies: A decade (2006–2016)

text: Abstract This review presents a retrospective of the studies carried out in the last 10 years (2006–2016) using spectroscopic methods as a research tool in the field of virology. Spectroscopic analyses are sensitive to variations in the biochemical composition of the sample, are non-destructive, fast and require the least sample preparation, making spectroscopic techniques tools of great interest in biological studies. Herein important chemometric algorithms that have been used in virological studies are also evidenced as a good alternative for analyzing the spectra, discrimination and classification of samples. Techniques that have not yet been used in the field of virology are also suggested. This methodology emerges as a new and promising field of research, and may be used in the near future as diagnosis tools for detecting diseases caused by viruses.


title: Association of Increased Prenatal Estrogen With Risk Factors for Schizophrenia

text: The author previously described a theoretical cause of schizophrenia based on the effects of estrogenic endocrine disruption. In the current review, the author describes how increased estrogen during pregnancy increases susceptibility to certain viral infections associated with increased risk for schizophrenia. The review further discusses how prenatal estrogen exposure could explain associations of schizophrenia with autoimmune diseases, urban environments, and stress. Based on the association of increased estrogen with schizophrenia risk factors, the author proposes increased prenatal estrogen as a unifying factor, perhaps the primary event, in the etiology of schizophrenia.


“COVIDphobia” influences early otolaryngology diagnoses


Applause for telemedicine as an optimal platform for specific menopausal health-care visits beyond COVID-19


Liaisons Dangereuses? new drugs, physicians and the drug industry