title: A Murine and a Porcine Coronavirus Are Released from Opposite Surfaces of the Same Epithelial Cells

text: Abstract Epithelial cells are important target cells for coronavirus infection. Earlier we have shown that transmissible gastroenteritis coronavirus (TGEV) and mouse hepatitis coronavirus (MHV) are released from different sides of porcine and murine epithelial cells, respectively. To study the release of these viruses from the same cells, we constructed a porcine LLC-PK1 cell line stably expressing the recombinant MHV receptor cDNA (LMR cells). The MHV and TGEV receptor glycoproteins were shown by immunofluorescence to appear at the surface of the cells and to be functional so that the cells were susceptible to both MHV and TGEV infection. Both coronaviruses entered polarized LMR cells only through the apical surface. Remarkably, while the cells remained susceptible to TGEV for long periods, infectability by MHV decreased with time after plating of the cells onto filters. This was not due to a lack of expression of the MHV receptor, since this glycoprotein was still abundant on the apical surface of these cells. TGEV and MHV appeared to exit LMR cells from opposite sides. Whereas TGEV was released preferentially at the apical membrane, MHV was released preferentially at the basolateral surface. These results show that vesicles containing the two coronaviruses are targeted differently in LMR cells. We propose that the viruses are sorted at the Golgi complex into different transport vesicles that carry information directing them to one of the two surface domains. The apical release of TGEV and the basolateral release of MHV might be factors contributing to the difference in virus spread found between TGEV and MHV in their respective natural hosts, the former causing mainly a localized enteric infection, the latter spreading through the body to other organs.


title: Host Translation at the Nexus of Infection and Immunity

text: By controlling gene expression at the level of mRNA translation, organisms temporally and spatially respond swiftly to an ever-changing array of environmental conditions. This capacity for rapid response is ideally suited for mobilizing host defenses and coordinating innate responses to infection. Not surprisingly, a growing list of pathogenic microbes target host mRNA translation for inhibition. Infection with bacteria, protozoa, viruses, and fungi has the capacity to interfere with ongoing host protein synthesis and thereby trigger and/or suppress powerful innate responses. This review discusses how diverse pathogens manipulate the host translation machinery and the impact of these interactions on infection biology and the immune response.


title: A SARS DNA Vaccine Induces Neutralizing Antibody and Cellular Immune Responses in Healthy Adults in a Phase I Clinical Trial

text: BACKGROUND: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8,000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. METHODS: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays. RESULTS: The vaccine was well-tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T cell responses were detected in all vaccinees, and CD8+ T cell responses in ∼20% of individuals. CONCLUSIONS: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.


title: Development of a Portable, Ultra-Rapid and Ultra-Sensitive Cell-Based Biosensor for the Direct Detection of the SARS-CoV-2 S1 Spike Protein Antigen

text: One of the key challenges of the recent COVID-19 pandemic is the ability to accurately estimate the number of infected individuals, particularly asymptomatic and/or early-stage patients. We herewith report the proof-of-concept development of a biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus. The biosensor is based on membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody. We demonstrate that the attachment of the protein to the membrane-bound antibodies resulted in a selective and considerable change in the cellular bioelectric properties measured by means of a Bioelectric Recognition Assay. The novel biosensor provided results in an ultra-rapid manner (3 min), with a detection limit of 1 fg/mL and a semi-linear range of response between 10 fg and 1 μg/mL. In addition, no cross-reactivity was observed against the SARS-CoV-2 nucleocapsid protein. Furthermore, the biosensor was configured as a ready-to-use platform, including a portable read-out device operated via smartphone/tablet. In this way, we demonstrate that the novel biosensor can be potentially applied for the mass screening of SARS-CoV-2 surface antigens without prior sample processing, therefore offering a possible solution for the timely monitoring and eventual control of the global coronavirus pandemic.


title: Viral interference between H9N2-low pathogenic avian influenza virus and avian infectious bronchitis virus vaccine strain H120 in vivo

text: Abstract The interaction between a low pathogenic avian influenza virus (A/CK/TUN/145/2012), a H9N2 Tunisian isolate, and a vaccine strain (H120) of avian infectious bronchitis, administered simultaneously or sequentially three days apart to chicks during 20 days, was evaluated using ELISA antibody levels, quantitative reverse transcription–polymerase chain reaction (qRT-PCR) analyses and histopathology examination. First, the in vivo replication interference of avian influenza virus (AIV) and infectious bronchitis virus (IBV) was evaluated using qRT-PCR to detect accurately either AIV or IBV genomes or viral copy numbers during dual infections. Second, we have determined the amount of specific antibodies in sera of chick’s infected with AIV alone, IBV alone, mixed AIV + IBV, IBV then AIV or AIV IBV 3 days later using an ELISA test. Finally, histopathological analyses of internal organs from inoculated chicks were realized. Quantitative results of AIV and IBV co-infection showed that interferences between the two viruses yielded decreased viral growth. However, in the case of super-infection, the second virus, either AIV or IBV, induced a decrease in the growth of the first inoculated virus. According to our results, vaccine application was safe and do not interfere with AIV H9N2 infection, and does not enhance such infection. In conclusion, co-infection of chicks with AIV and IBV, simultaneously or sequentially, affected the clinical signs, the virus replication dynamics as well as the internal organ integrity. The results proposed that infection with heterologous virus may result in temporary competition for cell receptors or competent cells for replication, most likely interferon-mediated.


title: Autophagy in viral replication and pathogenesis

text: Autophagy is a catabolic process that is important for the removal of damaged organelles and long-lived proteins for the maintenance of cellular homeostasis. It can also serve as innate immunity to remove intracellular microbial pathogens. A growing list of viruses has been shown to affect this cellular pathway. Some viruses suppress this pathway for their survival, while others enhance or exploit this pathway to benefit their replication. The effect of viruses on autophagy may also sensitize cells to death or enhance cell survival and play a critical role in viral pathogenesis. In this article, we review the relationships between different viruses and autophagy and discuss how these relationships may affect viruses and their host cells.


title: Pandemic clinical case definitions are non-specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia

text: BACKGROUND: During the early phases of the 2009 pandemic, subjects with influenza-like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus. FINDINGS: Between 25(th) May and 7(th) June 2009, during the pandemic CONTAIN phase, A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466 (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09 testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative samples were tested for other respiratory viruses using a real-time multiplex PCR assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of samples. CONCLUSIONS: In the very early stages of a new pandemic, limiting testing to only the novel virus will miss other clinically important co-circulating respiratory pathogens.


title: The effects of injection of bovine vaccine into a human digit: a case report

text: BACKGROUND: The incidence of needlestick injuries in farmers and veterinary surgeons is significant and the consequences of such an injection can be serious. CASE PRESENTATION: We report accidental injection of bovine vaccine into the base of the little finger. This resulted in increased pressure in the flexor sheath causing signs and symptoms of ischemia. Amputation of the digit was required despite repeated surgical debridement and decompression. CONCLUSION: There have been previous reports of injection of oil-based vaccines into the human hand resulting in granulomatous inflammation or sterile abscess and causing morbidity and tissue loss. Self-injection with veterinary vaccines is an occupational hazard for farmers and veterinary surgeons. Injection of vaccine into a closed compartment such as the human finger can have serious sequelae including loss of the injected digit. These injuries are not to be underestimated. Early debridement and irrigation of the injected area with decompression is likely to give the best outcome. Frequent review is necessary after the first procedure because repeat operations may be required.


Enhancing preparedness for tackling new epidemic threats


docid: pbnfrkwy

title: Epidemics in Partially Overlapped Multiplex Networks

text: Many real networks exhibit a layered structure in which links in each layer reflect the function of nodes on different environments. These multiple types of links are usually represented by a multiplex network in which each layer has a different topology. In real-world networks, however, not all nodes are present on every layer. To generate a more realistic scenario, we use a generalized multiplex network and assume that only a fraction [Image: see text] of the nodes are shared by the layers. We develop a theoretical framework for a branching process to describe the spread of an epidemic on these partially overlapped multiplex networks. This allows us to obtain the fraction of infected individuals as a function of the effective probability that the disease will be transmitted [Image: see text]. We also theoretically determine the dependence of the epidemic threshold on the fraction [Image: see text] of shared nodes in a system composed of two layers. We find that in the limit of [Image: see text] the threshold is dominated by the layer with the smaller isolated threshold. Although a system of two completely isolated networks is nearly indistinguishable from a system of two networks that share just a few nodes, we find that the presence of these few shared nodes causes the epidemic threshold of the isolated network with the lower propagating capacity to change discontinuously and to acquire the threshold of the other network.


title: A new paradigm: innate immune sensing of viruses via the unfolded protein response

text: The immune system depends upon combinations of signals to mount appropriate responses: pathogen specific signals in the context of co-stimulatory “danger” signals drive immune strength and accuracy. Viral infections trigger anti-viral type I interferon (IFN) responses by stimulating endosomal and cytosolic pattern recognition receptors (PRRs). However, viruses have also evolved many strategies to counteract IFN responses. Are there intracellular danger signals that enhance immune responses to viruses? During infection, viruses place a heavy demand on the protein folding machinery of the host endoplasmic reticulum (ER). To survive ER stress, host cells mount an unfolded protein response (UPR) to decrease ER protein load and enhance protein-folding capacity. Viruses also directly elicit the UPR to enhance their replication. Increasing evidence supports an intersection between the host UPR and inflammation, in particular the production of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro-inflammatory cytokine transcription factors and dramatically enhances cytokine production in response to viral PRR engagement. Additionally, viral PRR engagement may stimulate specific pathways within the UPR to enhance cytokine production. Through these mechanisms, viral detection via the UPR and inflammatory cytokine production are intertwined. Consequently, the UPR response is perfectly poised to act as an infection-triggered “danger” signal. The UPR may serve as an internal “co-stimulatory” signal that (1) provides specificity and (2) critically augments responses to overcome viral subterfuge. Further work is needed to test this hypothesis during viral infections.


title: Considerations on Biologicals for Patients with allergic disease in times of the COVID‐19 pandemic: an EAACI Statement

text: The outbreak of the SARS‐CoV‐2‐induced Coronavirus Disease 2019 (COVID‐19) pandemic re‐shaped doctor‐patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant numberof the patients are on treatment with biologicals and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS‐CoV‐2 is not known. Severe COVID‐19 patients may experience a “cytokine storm” and associated organ damage characterized by an exaggerated release of proinflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti‐inflammatory cytokines and type 2 responses. This expert based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID‐19 with studies focusing on severe allergic phenotypes lacking. At present, non‐infected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self‐application. In case of an active SARS‐CoV‐2 infection, biological treatment needs to be stopped until clinical recovery and SARS‐CoV‐2 negativity is established and treatment with biologicals should be re‐initiated. Maintenance of add‐on therapy and a constant assessment of disease control, apart from acute management is demanded.


title: Antibody induction after combined application of an adjuvanted recombinant FeLV vaccine and a multivalent modified live virus vaccine with a chlamydial component

text: The compatibility, safety and interaction on antibody induction of a combined vaccine application were assessed. Specific pathogen-free cats were vaccinated with either a modified live virus vaccine containing feline calici- (FCV), herpes- (FHV-1), parvovirus (FPV) and Chlamydophila felis (C. felis), an adjuvanted recombinant feline leukaemia virus (FeLV) vaccine or both vaccines in one syringe. After combined application, FeLV ELISA antibody titres were unaltered, However antibody production based on indirect immunofluorescence assay was remarkably enhanced for FCV and was at selected time points also enhanced for FHV-1 and C. felis but diminished for FPV. The use of these vaccines in combination was safe and will simplify vaccination schedules in veterinary practice.


title: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review

text: INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.


title: LeishVet update and recommendations on feline leishmaniosis

text: Limited data is available on feline leishmaniosis (FeL) caused by Leishmania infantum worldwide. The LeishVet group presents in this report a review of the current knowledge on FeL, the epidemiological role of the cat in L. infantum infection, clinical manifestations, and recommendations on diagnosis, treatment and monitoring, prognosis and prevention of infection, in order to standardize the management of this disease in cats. The consensus of opinions and recommendations was formulated by combining a comprehensive review of evidence-based studies and case reports, clinical experience and critical consensus discussions. While subclinical feline infections are common in areas endemic for canine leishmaniosis, clinical illness due to L. infantum in cats is rare. The prevalence rates of feline infection with L. infantum in serological or molecular-based surveys range from 0 % to more than 60 %. Cats are able to infect sand flies and, therefore, they may act as a secondary reservoir, with dogs being the primary natural reservoir. The most common clinical signs and clinicopathological abnormalities compatible with FeL include lymph node enlargement and skin lesions such as ulcerative, exfoliative, crusting or nodular dermatitis (mainly on the head or distal limbs), ocular lesions (mainly uveitis), feline chronic gingivostomatitis syndrome, mucocutaneous ulcerative or nodular lesions, hypergammaglobulinaemia and mild normocytic normochromic anaemia. Clinical illness is frequently associated with impaired immunocompetence, as in case of retroviral coinfections or immunosuppressive therapy. Diagnosis is based on serology, polymerase chain reaction (PCR), cytology, histology, immunohistochemistry (IHC) or culture. If serological testing is negative or low positive in a cat with clinical signs compatible with FeL, the diagnosis of leishmaniosis should not be excluded and additional diagnostic methods (cytology, histology with IHC, PCR, culture) should be employed. The most common treatment used is allopurinol. Meglumine antimoniate has been administered in very few reported cases. Both drugs are administered alone and most cats recover clinically after therapy. Follow-up of treated cats with routine laboratory tests, serology and PCR is essential for prevention of clinical relapses. Specific preventative measures for this infection in cats are currently not available.


title: Influenza C Virus in Cattle with Respiratory Disease, United States, 2016–2018

text: We identified influenza C virus (ICV) in samples from US cattle with bovine respiratory disease through real-time PCR testing and sequencing. Bovine ICV isolates had high nucleotide identities (≈98%) with each other and were closely related to human ICV strains (≈95%). Further research is needed to determine bovine ICV’s zoonotic potential.


title: Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71

text: Abstract In this study, aloe-emodin was identified as a potential interferon (IFN)-inducer by screening compounds from Chinese herbal medicine. Aloe-emodin showed low cytotoxicity to human HL-CZ promonocyte cells and TE-671 medulloblastoma cells and significantly activated interferon-stimulated response element (ISRE) and gamma-activated sequence (GAS)-driven cis-reporting systems. Moreover, aloe-emodin upregulated expression of IFN-stimulated genes such as dsRNA-activated protein kinase and 2′,5′-oligoisoadenylate synthase. Aloe-emodin resulted in significant activation of nitric oxide production. The antiviral activity of aloe-emodin against Japanese encephalitis virus (JEV) and enterovirus 71 (EV71) was evaluated using dose- and time-dependent plaque reduction assays in HL-CZ cells and TE-671 cells. The 50% inhibitory concentration (IC50) of aloe-emodin ranged from 0.50μg/mL to 1.51μg/mL for JEV and from 0.14μg/mL to 0.52μg/mL for EV71. Aloe-emodin showed clearly potent virus inhibitory abilities and achieved high therapeutic indices, in particular for HL-CZ cells. Therefore, the study demonstrated dose- and time-dependent actions of aloe-emodin on the inhibition of JEV and EV71 replication via IFN signalling responses.


title: Applications of the Phytomedicine Echinacea purpurea (Purple Coneflower) in Infectious Diseases

text: Extracts of Echinacea purpurea (EP, purple coneflower) have been used traditionally in North America for the treatment of various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition, they display multiple immune-modulatory activities, comprising stimulation of certain immune functions such as phagocytic activity of macrophages and suppression of the proinflammatory responses of epithelial cells to viruses and bacteria, which are manifested as alterations in secretion of various cytokines and chemokines. These immune modulations result from upregulation or downregulation of the relevant genes and their transcription factors. All these bioactivities can be demonstrated at noncytotoxic concentrations of extract and appear to be due to multiple components rather than the individual chemical compounds that characterize Echinacea extracts. Potential applications of the bioactive extracts may go beyond their traditional uses.


Cardiovascular Health in the COVID-19 Era: A Call for Action and Education


title: Antibacterial performance of photocatalyst thin film fabricated by defection effect in visible light

text: Abstract We have developed a new photocatalyst thin film that has strong antibacterial action in visible light. In this study the radiofrequency (RF) sputter technique was used to deposit a defective titanium dioxide (TiO x , x < 2) photocatalyst thin film (120 nm thickness) on glass and steel substrates. In the ultraviolet (UV)-visible spectrum analysis, the defective TiO x thin film was found to generate the red shift effect. To determine whether the defective TiO x thin film has antibacterial ability under visible light, we designed a series of experiments according to the Japanese Industrial Standards (JIS) Committee standard for testing antibacterial performance and for exploring the impact of surface roughness of substrate. Our results show that the antibacterial performance rate against Escherichia coli could reach 99.99% in visible light. We also proved that the coating technology can be applied effectively to surfaces with different degrees of roughness. It is suitable for protecting both human health and the natural environment.


title: Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia

text: Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.


title: Chapter 36 SARS

text: Abstract Five years after the first severe acute respiratory syndrome (SARS) outbreak, several candidate SARS-coronavirus (CoV) vaccines are at various stages of preclinical and clinical development. Based on the observation that SARSCoV infection is efficiently controlled upon passive transfer of antibodies directed against the spike (S) protein of SARS-CoV, vaccines containing the S protein have been formulated. Animals immunized with inactivated whole virus vaccines or live-recombinant vaccines expressing the SARS-CoV S protein (e.g., using rabies virus, vesicular stomatitis virus, bovine parainfluenza virus type 3, adenovirus, or attenuated vaccinia virus MVA as a vector), as well as mice immunized with DNA vaccines expressing the S protein gene all developed neutralizing antibodies to SARS-CoV and were protected against SARS-CoV challenge. Although much effort has been focused on developing a SARS vaccine, the commercial viability of such a vaccine for SARS-CoV will ultimately depend on whether the virus re-emerges in the near future. This vaccine should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. Given the fact that in the previous outbreak mainly the elderly succumbed to the infection, special attention should be given to vaccines that are able to efficiently protect aged individuals.


title: A Guide for Oncologic Patient Management during Covid-19 Pandemic: The Initial Experience of an Italian Oncologic Hub with Exemplificative Focus on Uro-Oncologic Patients

text: The recent exponential increase in the number of COVID-19 patients in Italy led to the adoption of specific extraordinary measures, such as the need to convey treatment of all non-deferrable cancer patients to specialized centres (hubs). We reported a comprehensive summary of guidelines to create and run an oncologic hub during the COVID-19 pandemic. Oncologic hubs must fulfil some specific requirements such as a high experience in oncologic patient treatment, strict strategies applied to remain a “COVID-19-free” centre, and the creation of a dedicated multidisciplinary “hub team”. Cancer treatment of patients who belong to external centres, namely spoke centres, could be organized in different pathways according to the grade of involvement and/or availability of the medical team of the spoke centre. Moreover, dedicated areas should be created for the management and treatment of patients who developed COVID-19 symptoms after hospitalization (i.e., dedicated wards, operation rooms and intensive care beds). Lastly, hospital staff must be highly trained for both preventing COVID-19 contagion and treating patients who develop the infection. We provided a simplified, but complete and easily applicable guide. We believe that this guide could help those clinicians who have to treat oncologic patients during the COVID-19 pandemic.


Europe's response to COVID-19 in March and April 2020 - A letter to the editor on “World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)” (Int J Surg 2020;76:71-6)


title: Materials from peptide assembly: towards the treatment of cancer and transmittable disease

text: As the prevalence of cancer and transmittable disease persists, the development of new and more advanced therapies remains a priority in medical research. An emerging platform for the treatment of these illnesses is the use of materials formed via peptide assembly where the bulk material itself acts as the therapeutic. Higher ordered peptide structures with defined chemistry are capable of cellular targeting, recognition, and internalization. Recent design efforts are being made to exploit the nanoscale definition of the materials formed by assembling peptides to target cancer and microbial cells and to function as vaccines. This review focuses on assembled peptide materials that actively participate in the biological processes important to cancer and transmittable diseases to exert an anticipated functional outcome.


Pneumomediastinum related to Covid-19 pneumonia


title: Exhaled Air Dispersion Distances During Noninvasive Ventilation via Different Respironics Face Masks

text: Background As part of our influenza pandemic preparedness, we studied the exhaled air dispersion distances and directions through two different face masks (Respironics; Murrysville, PA) attached to a human-patient simulator (HPS) during noninvasive positive-pressure ventilation (NPPV) in an isolation room with pressure of −5 Pa. Methods The HPS was positioned at 45° on the bed and programmed to mimic mild lung injury (oxygen consumption, 300 mL/min; lung compliance, 35 mL/cm H2O). Airflow was marked with intrapulmonary smoke for visualization. Inspiratory positive airway pressure (IPAP) started at 10 cm H2O and gradually increased to 18 cm H2O, whereas expiratory pressure was maintained at 4 cm H2O. A leakage jet plume was revealed by a laser light sheet, and images were captured by high definition video. Normalized exhaled air concentration in the plume was estimated from the light scattered by the smoke particles. Findings As IPAP increased from 10 to 18 cm H2O, the exhaled air of a low normalized concentration through the ComfortFull 2 mask (Respironics) increased from 0.65 to 0.85 m at a direction perpendicular to the head of the HPS along the median sagittal plane. When the IPAP of 10 cm H2O was applied via the Image 3 mask (Respironics) connected to the whisper swivel, the exhaled air dispersed to 0.95 m toward the end of the bed along the median sagittal plane, whereas higher IPAP resulted in wider spread of a higher concentration of smoke. Conclusions Substantial exposure to exhaled air occurs within a 1-m region, from patients receiving NPPV via the ComfortFull 2 mask and the Image 3 mask, with more diffuse leakage from the latter, especially at higher IPAP.


title: Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology

text: Abstract Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-γ (IFN-γ) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-γ transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1α and MIP-1β mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1α- and MIP-1β-driven macrophage immunopathology.


title: Results of Double Blind Placebo Controlled Trial to Assess the Effect of Vitamin B6 on Managing of Nausea and Vomiting In Pediatrics with Acute Gastroenteritis

text: BACKGROUND: Gastroenteritis and respiratory tract infections are the most common childhood diseases. Despite the common use of vitamin B6 to control vomiting in children with gastroenteritis, no study has been performed in this field. This study aimed to assess the value of vitamin B6 in the prevention of vomiting in patients with mild to moderate gastroenteritis. METHODOLOGY: This study was a double blind controlled clinical trial on 96 children with mild to moderate gastroenteritis with age range of 6 months to 12 years admitted in Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients were randomly assigned to two groups of 48 subjects matched for age, sex and symptoms of dehydration. Vitamin B6 was given in case group and control group was given placebo. The severity of dehydration and vomiting in patients before and after treatment were evaluated by a physician. All data were recorded in the questionnaire and results in the two treatment groups were compared by using SPSS software (Version 15, Chicago, IL, USA). RESULTS: The mean ± SD age of patients whom underwent Vitamin B6 treatment was 2.9±2.4 versus 2.5±2 in placebo group. Significant difference between mean age, gender, and severity of dehydration in children of two groups wasn’t observed. After treatment in both treatment groups, 40 patients (83.3%) had mild dehydration, and 8 patients (16.7%) had moderate dehydration. Vomiting was noted in 28 patients (58.3%) after treatment with vitamin B6 and in 37 patients (77.1%) after treatment with placebo. The mean frequency of vomiting after treatment with vitamin B6 was 1.7±1.3 times and in the control group (treated with distilled water) was 1.5±0.77 time, but no significant difference between the severity of dehydration, controlling vomiting and the mean frequency of vomiting was observed in both groups (P>0.05). CONCLUSION: It seems that the use of oral vitamin B6 treatment has no benefit and impact compared with the placebo. Thus, use of vitamin B6 in the prevention of vomiting due to acute mild to moderate gastroenteritis is not only scientifically, but in the present study it was proved to be ineffective. This work was done on a comparative basis and further researches are recommended.


title: Pertussis: The Identify, Isolate, Inform Tool Applied to a Re-emerging Respiratory Illness

text: Pertussis, commonly referred to as “whooping cough,” is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel “Identify, Isolate, Inform” (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive “whooping cough.” This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness.


title: Statistical and network analysis of 1212 COVID-19 patients in Henan, China

text: Abstract Background COVID-19 is spreading quickly all over the world. Publicly released data for 1212 COVID-19 patients in Henan of China was analyzed in this paper. Methods Various statistical and network analysis methods were employed. Results We found that COVID-19 patients show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences, possible causes were explored; The estimated average, mode and median incubation periods are 7.4, 4 and 7 days; Incubation periods of 92% patients were no more than 14 days; The epidemic in Henan has undergone three stages and showed high correlations with the numbers of patients recently return from Wuhan; Network analysis revealed that 208 cases were clustering infected and various people's Hospitals are the main force in treating COVID-19. Conclusions The incubation period was statistical estimated and the proposed state transition diagram can well explore the epidemic stages of emerging infectious disease. We suggest that though the quarantine measures are gradually at work, strong measures might be still needed for a period of time, since ∼7.45% patients may have very long incubation periods. Migrant workers or college students are with high risk. State transition diagram can help us to recognize the time-phased nature of epidemic. Our investigations have implications for the prevention and control of COVID-19 in other regions of the world.


docid: apdyaujt

title: In vivo and in vitro models of demyelinating diseases XII. Persistence and expression of corona JHM vims functions in RN2-2 Schwannoma cells during latency

text: Abstract The coronavirus JHMV persistently infects rat Schwannoma cells RN2-2 at 32.5°C and enters a host-imposed reversible, latent state at 39.5°C. JHMV can remain up to 20 days in the latent state and about 14 days before the cultures lose the capacity to resume virus production upon return to 32.5°C. Although persistently and latently infected RN2-2 cells display resistance to superinfection by a heterologous agent VSV, these cells do not release detectable soluble mediators (e.g., interferon) of the antiviral state. Nevertheless, RN2-2 cells are competent to synthesize and release interferon when treated with the appropriate inducers. These observations suggest that interferon does not play any role or may not be the major factor in the control of latency in the Schwannoma cell. Hybridization with virus-specific cDNAs shows that all viral mRNAs are present during latency and that viral mRNAs are present in the polysomes of infected cells at 39.5°C. Western immunoblotting with hybridoma antibodies demonstrates that viral specific proteins are produced at the restrictive temperature. These results


title: Forecasting respiratory infectious outbreaks using ED-based syndromic surveillance for febrile ED visits in a Metropolitan City

text: Abstract Background Monitoring and detecting sudden outbreaks of respiratory infectious disease is important. Emergency Department (ED)-based syndromic surveillance systems have been introduced for early detection of infectious outbreaks. The aim of this study was to develop and validate a forecasting model of respiratory infectious disease outbreaks based on a nationwide ED syndromic surveillance using daily number of emergency department visits with fever. Methods We measured the number of daily ED visits with body temperature ≥ 38.0 °C and daily number of patients diagnosed as respiratory illness by the ICD-10 codes from the National Emergency Department Information System (NEDIS) database of Seoul, Korea. We developed a forecast model according to the Autoregressive Integrated Moving Average (ARIMA) method using the NEDIS data from 2013 to 2014 and validated it using the data from 2015. We defined alarming criteria for extreme numbers of ED febrile visits that exceed the forecasted number. Finally, the predictive performance of the alarm generated by the forecast model was estimated. Results From 2013 to 2015, data of 4,080,766 ED visits were collected. 303,469 (7.4%) were ED visits with fever, and 388,943 patients (9.5%) were diagnosed with respiratory infectious disease. The ARIMA (7.0.7) model was the most suitable model for predicting febrile ED visits the next day. The number of patients with respiratory infectious disease spiked concurrently with the alarms generated by the forecast model. Conclusions A forecast model using syndromic surveillance based on the number of ED visits was feasible for early detection of ED respiratory infectious disease outbreak.


title: Effect of maternal cells transferred with colostrum on the health of neonate calves

text: Abstract The objective of this research was to evaluate the influence of cells from colostrum on the health of neonate calves. Animals were distributed in 2 groups: COL+ (n =9) which received fresh colostrum from their own damns; and COL− (n =10) which received frozen colostrums from donors. Heifers were assessed before colostrum intake – D0; D2; D7; D14; D21 and D28. Heifers were monitored by clinical examination, hematological profile and serum iron. COL− had a higher diarrhea intensity score (typically 3) on D7. Moreover, a single case each of bronchopneumonia and navel inflammation were observed in COL− calves. COL− had fewer red blood cells (RBC) (6.5±0.8×106/μL) and less hemoglobin (Hgb) (8.3±1.4g/dL) than COL+ (RBC=7.2±0.8×106/μL; Hgb=9.6±1.3g/dL) at D14 (P ≤0.05). COL− had more anemia on D21 (P =0.03) and on D28 (P =0.02). Iron was lower in COL− (5.6±2.7μM/L) than COL+ (10.7±6.2μM/L) (P =0.03) on D7. Lymphocytes was lower in COL− than COL+ on D7 (3.8±1.0×103/μL COL+ and 5.4±2.2×103/μL COL−, P =0.02). COL− calves had more anemia and lower serum iron concomitant with diarrhea on D7. The number of leukocytes was relatively consistent in the COL+ calves, while COL− calves showed an increasing number of of lymphocytes starting on D7.


title: Antibiotic resistance amongst healthcare-associated pathogens in China

text: Abstract The People's Republic of China, commonly known as China, comprises approximately one-fifth of the world's population. Because of the expanding size and density of its population and the frequent interaction of people with animals, China is a hotspot for the emergence and spread of new microbial threats and is a major contributor to the worldwide infectious disease burden. In recent years, the emergence and rapid spread of severe acute respiratory syndrome (SARS) generated considerable interest in the Chinese healthcare system and its infection control and prevention measures. This review examines antibiotic misuse and the status of antibiotic resistance in the Chinese healthcare system. China has high rates of antibiotic resistance driven by misuse of these agents in a healthcare system that provides strong incentives for overprescribing and in a country where self-medication is common. Tuberculosis remains a serious problem in China, with a high prevalence of multidrug-resistant and extensively drug-resistant strains. Drug resistance amongst nosocomial bacteria has been on a rapid upward trend with a strong inclination towards multidrug resistance. There is a need for effective infection prevention and control measures and strict use of antibiotics in China to control the rise and spread of antibiotic resistance in the country.


COVID-19: A Preparation Guide for Anesthesiologists


title: Porcine Intestinal Enteroids: a New Model for Studying Enteric Coronavirus Porcine Epidemic Diarrhea Virus Infection and the Host Innate Response

text: Porcine epidemic diarrhea virus (PEDV), a member of the group of alphacoronaviruses, is the pathogen of a highly contagious gastrointestinal swine disease. The elucidation of the events associated with the intestinal epithelial response to PEDV infection has been limited by the absence of good in vitro porcine intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Here, we generated swine enteroids from the intestinal crypt stem cells of the duodenum, jejunum, or ileum and found that the generated enteroids are able to satisfactorily recapitulate the complicated intestinal epithelium in vivo and are susceptible to infection by PEDV. PEDV infected multiple types of cells, including enterocytes, stem cells, and goblet cells, and exhibited segmental infection discrepancies compared with ileal enteroids and colonoids, and this finding was verified in vivo. Moreover, the clinical isolate PEDV-JMS propagated better in ileal enteroids than the cell-adapted isolate PEDV-CV777, and PEDV infection suppressed interferon (IFN) production early during the infection course. IFN lambda elicited a potent antiviral response and inhibited PEDV in enteroids more efficiently than IFN alpha (IFN-α). Therefore, swine enteroids provide a novel in vitro model for exploring the pathogenesis of PEDV and for the in vitro study of the interplay between a host and a variety of swine enteric viruses. IMPORTANCE PEDV is a highly contagious enteric coronavirus that causes significant economic losses, and the lack of a good in vitro model system is a major roadblock to an in-depth understanding of PEDV pathogenesis. Here, we generated a porcine intestinal enteroid model for PEDV infection. Utilizing porcine intestinal enteroids, we demonstrated that PEDV infects multiple lineages of the intestinal epithelium and preferably infects ileal enteroids over colonoids and that enteroids prefer to respond to IFN lambda 1 over IFN-α. These events recapitulate the events that occur in vivo. This study constitutes the first use of a primary intestinal enteroid model to investigate the susceptibility of porcine enteroids to PEDV and to determine the antiviral response following infection. Our study provides important insights into the events associated with PEDV infection of the porcine intestine and provides a valuable in vitro model for studying not only PEDV but also other swine enteric viruses.


title: Global transmission network of SARS-CoV-2: from outbreak to pandemic

text: BACKGROUND. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on people’s movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. METHODS. We employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. RESULTS AND CONCLUSIONS. The analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures.


title: Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan

text: BACKGROUND: The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. RESULTS: A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. CONCLUSION: The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003.


title: An alternative methodology for planning baggage carousel capacity expansion: A case study of Incheon International Airport

text: Abstract Intensifying competition for air transportation passengers has led airports to research optimal designs and determine the infrastructure expansion capacities of their terminals. As a result, many researchers have studied this subject from a variety of perspectives. In this study, we propose an alternative methodology of determining the expansion of baggage carousel capacity over a series of steps that includes both a simulation and a cost-benefit analysis. The methodology consists of three stages. In the first stage, we forecast the volume of arriving passengers (excluding transfer passengers) and aircraft traffic with an autoregressive integrated moving average (ARIMA) model. Next, we conduct an elaborate analysis to estimate passenger delay using a discrete event simulation model in which we consider the conveyor load and the baggage carousel allocation to aircraft rates. Finally, we determine a plan to expand baggage carousel capacity that accounts for expansion costs and passenger benefits. Construction and conveyor costs were applied to expansion costs, and capacity expansion leads to passenger benefits due to reduced waiting time. Using a real case with 23 candidate baggage carousels at Incheon International Airport during 2013–2015, our experiments demonstrate the strength of the proposed methodology in planning appropriate capacity expansion that reflect the operational flow of passengers within the airport based on the future trend of passenger demand. In particular, our results show that carousel no. 18 should be expanded during the first quarter of 2013, carousels no. 17 and no. 19 should be expanded in 2014, and carousel no. 5 should be expanded in 2015 to obtain optimal benefit-cost ratios of 1.65, 1.79, and 1.76 for each year, respectively.


title: Considerations of coronavirus (COVID-19) impact and the management of the dead in Brazil

text: Abstract During a pandemic such as COVID-19, the forensic community plays a key role in the management of the crisis, both nationally and internationally. Much has been written and disseminated regarding protocols for death investigation, infection mitigation and risks, and management of dead. However, in many contexts, the ability of forensic practitioners to follow best-practice procedures is limited by the resources available to them. This article examines some of the impact of the novel coronavirus (COVID-19) in Brazil, with emphasis on management of the dead and challenges faced by medicolegal services.


docid: stbyyyuh

title: Phylogenetic analysis of the S1 glycoprotein gene of infectious bronchitis viruses isolated in China during 2009–2010

text: As part of our ongoing surveillance program, 40 field strains of avian infectious bronchitis virus (IBV) were isolated from dead or diseased chicken flocks in different areas of China between 2009 and 2010. S1 glycoprotein genes of these strains were sequenced and analyzed with 38 strains published in GenBank. S1 genes of these isolated strains and the vaccine strains showed nucleotide homologies ranging from 65.2 to 82% and amino acid homologies ranging from 58.4 to 81.9%. Meanwhile, Chinese IBV strains isolated in this study, which were mainly nephropathogenic, could be separated into six variant lineages (CH I–CH VI), and current vaccine strains used in China formed Mass variant lineage that is evolutionarily distant from Chinese isolates. Moreover, CK/CH/GD/NC10, CK/CH/GD/KP10, and our previous isolates TC07-2 formed the CH VI lineage, showing larger evolutionary distances from other strains. Taken together, these findings suggested that various variant lineages were co-circulating in China now, and appeared to be continuously evolving, alternative indigenous vaccines indeed need for effective control of IB in China.


title: Sacituzumab Govitecan: First Approval

text: Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.


docid: wrszeqwa

title: A Call to Arms: Emergency Hand and Upper Extremity Operations During the COVID-19 Pandemic

text: ABSTRACT Purpose Limited data exist regarding volumetric trends and management of upper extremity emergencies during periods of social restriction and duress, such as the COVID-19 pandemic. We sought to study the effect of shelter-in-place orders on emergent operative upper extremity surgery. Methods All patients undergoing emergent and time-sensitive operations to the finger(s), hand, wrist and forearm were tracked over an equal number of days before and after shelter-in-place orders at two geographically distinct Level 1 trauma centers. Surgical volume and resources, patient demographics, and injury patterns were compared before and after official shelter-in-place orders. Results Fifty-eight patients underwent time-sensitive or emergent operations. The mean patient age was 42 years with mean injury severity score (ISS) of 9 and median ASA score of 2. There was a 40% increase in volume after shelter-in-place orders, averaging 1.4 cases per day. Indications for surgery included high-energy closed fracture (60%), traumatic nerve injury (19%), severe soft tissue infection (15%), and revascularization of the arm, hand or digit(s) (15%). High-risk behavior, defined as lawlessness, assault, and high-speed auto accidents, was associated with a significantly greater proportion of operations after shelter-in-place orders (40% vs 12.5%, p<0.05). Each institution dedicated an average of three inpatient beds and one ICU capable bed to upper extremity care daily. Resources utilized included an average of 115 minutes of daily operating room time and 8 operating room staff/personnel per case. Conclusions Hand and upper extremity operative volume increased after shelter-in-place orders at two major Level 1 trauma centers across the country, demanding considerable hospital resources. The rise in volume was associated with an increase in high-risk behavior. Type of Study/Level of Evidence Therapeutic, Level IV


title: After the pandemic: Medium‐term growth uncertainties

text: ▪ The coronavirus is having a very large short‐term negative impact on world growth. But the medium‐term growth outlook is more uncertain. Much depends on the policy response ‐ a strong and well‐designed response could contain the medium‐term output losses, but large and enduring damage is a risk. ▪ Growth patterns after significant GDP declines vary. Historical evidence points to large upfront effects from pandemics and natural disasters, but the medium‐term outcomes are mixed, with policy responses a crucial determinant. Longer recessions and financial crises tend to lead to weaker medium‐term growth. ▪ The coronavirus may trigger annual GDP declines among the worst seen in the last 100 years. Economies can bounce back sharply after such declines, but our analysis suggests output losses also endure in a significant number of cases. ▪ The US interwar experience shows the danger of allowing financial distress to snowball and exacerbate GDP declines. The weakness of medium‐term growth after the global financial crisis confirms the long‐term impact of such distress. ▪ A key risk for the medium term is that firms and/or households react to the coronavirus recession and disruption by raising savings, accelerating a shift toward ‘Japanification’ of major economies. ▪ Our baseline forecasts envisage moderate medium‐term output losses due to coronavirus, in part reflecting rapid and large‐scale policy interventions. But uncertainty around this forecast is significant and considerable variation is possible across economies.


title: A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong

text: We conducted a six-year epidemiological study on human coronaviruses (HCoVs) circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77 (0.93%) of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43 (0.58%), followed by HCoV-229E (0.15%), HCoV-HKU1 (0.13%) and HCoV-NL63 (0.07%). HCoVs were detected throughout the study period (September 2008–August 2014), with the highest detection rate from September 2010 to August 2011 (22/1500, 1.47%). Different seasonal patterns of each HCoV species in Hong Kong were noted. HCoV-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years (range, 22 days to 95 years). Intriguingly, the detection rate of HCoV-OC43 in the age group of > 80 years (26/2380, 1.09%) was significantly higher than that in the age group of 0–10 years (12/2529, 0.47%) (P < 0.05). These data provides new insight into the epidemiology of coronaviruses. [Image: see text]


title: Prudently conduct the engineering and synthesis of the SARS-CoV-2 virus

text: Abstract Regarding to the recent work of engineering SARS-CoV-19 virus and the publication “Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform” by researchers at University of Bern, this paper comments on the “dual-use” problem and regulation issue of synthetic biology from the perspective of responsible (research and) innovation, biosafety and biosecurity. Based on the ethical and legal framework, the authors suggest to conduct such research with high potential risks prudently and responsibly.


title: An in silico map of the SARS-CoV-2 RNA Structurome

text: SARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis.


title: Leading and managing an emergency department—A personal view

text: Abstract The emergency department (ED) is a “unique operation, optimized to exist at the edge of chaos”. It is the responsibility of the leaders and managers of the ED to ensure that their teams work in an environment where they can deliver the best care to their patients. This environment is defined by people, system and place. People are the most important asset of the ED. One of the most important responsibilities of the ED leaders and managers (senior management) is to foster teamwork. They will also have to ensure that communication between team members is optimal and that there is a structure in place for conflict resolution. ED senior management should be aware of their team dynamics and know the “movers and shakers” in their organization. ED systems should be kept simple. One of the core businesses of an ED is contingency planning. ED senior management must plan, prepare, practice, review, analyze, assess and strategize for unexpected events. The ED physical environment has an impact on the flow of care being delivered to her patients. ED senior management must manage change. Change works only if it takes root in the hearts and minds of the organization's people. The quality of the leaders and managers of the ED will determine whether or not, their teams work in an environment where they can deliver the best care to their patients.


title: Proteinaceous cysteine protease inhibitors

text: Studies of proteinaceous cysteine protease inhibitors originated with the discovery of cystatins in the 1960s. Since that time, a rich and fascinating world of proteins that control and regulate a multitude of important physiological processes, ranging from the basics of protein turnover to development and brain function, has been uncovered. Failures in such important and complex systems inevitably lead to pathologies. Many threatening diseases such as cancer or neurological disorders, to mention only some, are attributed to deregulation of proteaseinhibitor balance. Moreover, important aspects of infection pathology and host defense rely on proteolysis and protease inhibition. Recent advances in the field of protease inhibitors have drawn attention to the possible use of this collected knowledge to control related pathological processes. This review attempts to familiarize the reader with proteinaceous cysteine protease inhibitors by providing an overview of current knowledge. The work primarily highlights biological processes in which the inhibitors are involved and focuses on pathologies resulting from aberrant protease-inhibitor balance, pointing out emerging possibilities for their correction.


title: Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization

text: Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.


title: Palliative care in the time of COVID-19

text: Abstract After covid-19 crisis in Italy, serious restrictions have been introduced for relatives, with limitations or prohibitions on hospital visits. To partially overcome these issues “WhatsApp” has been adopted to get family members to participate in clinical rounds. Family members of patients admitted to the acute palliative care unit and hospice were screened for a period of 2 weeks. Four formal questions were posed: 1) Are you happy to virtually attend the clinical round? 2) Are you happy with the information gained in this occasion? 3) Do you think that your loved one was happy to see you during the clinical rounds? 4) This technology may substitute your presence during the clinical rounds? The scores were 0 = no, 1 = a little bit, 2 = much, 3 = very much. Relatives were free to comment about these points. Sixteen of 25 screened family members were interviewed. Most family members had a good impression, providing scores of 2 or 3 for the first three items. However, the real presence bedside (forth question) was considered irreplaceable. They perceived that their loved one, when admitted to hospice, had to say good-bye before dying.


title: Pathogen prevalence in commercially reared bumble bees and evidence of spillover in conspecific populations

text: Abstract Worldwide, wild bumble bees (Bombus spp.) are experiencing marked declines, with potentially up to 11% of species currently under threat. Recent studies from North America suggest that disease transmission from commercially reared bumble bees to wild populations has led to marked range contractions in some species. In Europe, data on the prevalence of pathogen spillover from commercial to wild bumble bee populations is lacking, despite the widespread production and transport of hives within the EU since the early 1980s. We determined the permeability of cropping systems to commercial bumble bees, and quantified the prevalence of four pathogens in commercial Bombus terrestris hives and adjacent conspecific populations at increasing distances from greenhouses in Ireland. Commercial bumble bees collected from 31% to 97% of non-crop pollen, depending on the cropping system, and hives had markedly higher frequencies of two gut parasites, Crithidia spp. and Nosema bombi, compared to adjacent populations, but were free of tracheal mites. The highest prevalence of Crithida was observed within 2km of greenhouses and the probability of infection declined in a host sex- and pathogen-specific manner up to 10km. We suggest implementing measures that prevent the interaction of commercially reared and wild bumble bees by integrating the enforcement of national best management practices for users of commercial pollinators with international legislation that regulates the sanitation of commercial hives in production facilities.


title: Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

text: The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02787-2) contains supplementary material, which is available to authorized users.


title: NCI’s Work to Advance Cancer Research while Responding to the COVID-19 Pandemic

text: Abstract During the COVID-19 pandemic, the National Cancer Institute (NCI) is bringing to bear its considerable expertise and capabilities to understand, treat, and prevent the disease. While responding to the pandemic, NCI’s priority remains the advancement of cancer research. NCI has implemented many flexibilities for grantees and trainees.


title: Coronavirus surveillance of wildlife in the Lao People’s Democratic Republic detects viral RNA in rodents

text: Coronaviruses can become zoonotic, as in the case of COVID-19, and hunting, sale, and consumption of wild animals in Southeast Asia increases the risk for such incidents. We sampled and tested rodents (851) and other mammals and found betacoronavirus RNA in 12 rodents. The sequences belong to two separate genetic clusters and are closely related to those of known rodent coronaviruses detected in the region and distantly related to those of human coronaviruses OC43 and HKU1. Considering the close human-wildlife contact with many species in and beyond the region, a better understanding of virus diversity is urgently needed for the mitigation of future risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04683-7) contains supplementary material, which is available to authorized users.


Prevalence of coronavirus


title: Using the COVID-19 to influenza ratio to estimate the numbers of symptomatic COVID-19 cases in Wuhan prior to the lockdown

text: A recent study tested 45 throat swabs taken from adults over age 30 who sought outpatient care at one of two central Wuhan hospitals for influenza-like-illness between December 30, 2019 and January 19, 2020. Although none were confirmed COVID-19 cases, nine retrospectively tested positive for the virus. Using the fact that Wuhan has 393 other hospitals, we extrapolate the total number of undetected cases of symptomatic COVID-19 in adults during this period. we estimate that there were 5,558 [95% CI: 2,761-9,864] adults with symptomatic COVID-19 infections in Wuhan between December 30th and January 19th, 2020.


title: Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) Viral Spike Protein-Angiotensin Converting Enzyme-2 (ACE2) interaction

text: Commonly used drugs for treating many conditions are either natural products or derivatives. In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein. Here we argue that the oral route of administration of quercetin is unlikely to be effective in clinical trials owing to biotransformation during digestion, absorption and metabolism, but suggest that agents could be administered directly by alternative routes such as a nasal or throat spray.


Adaptation: An Interventional Radiology Residency Response to COVID-19


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title: Impact of RNA Virus Evolution on Quasispecies Formation and Virulence

text: RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.


title: Protein Microarrays and Biomarkers of Infectious Disease

text: Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.


title: A systems approach to natural disaster resilience

text: Abstract The frequency, social, and economic impacts of natural disasters show exponential increases in recent decades. Cities and countries around the world have begun to realize that these events are no longer “hundred year” storms, but repeat within a few years. As urbanisation continues throughout this century, more and more people and more economic activity will be concentrated in at-risk areas; especially as new arrivals in cities throughout Asia and Africa are likely to be concentrated in the highest risk districts, much as they often are in North America and Europe today. This article reviews recent growth of natural disasters and considers how a systems approach can improve approaches to mitigation and adaptation of these risks and to recovery from such events.


Whose responsibility? COVID‐19 in a homeless shelter in the UK


title: Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin

text: Abstract Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors (5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a replication model for severe acute respiratory syndrome (SARS) infections (Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K., Packard, M., Shieh, W.J., Zaki, S., Murphy, B., 2004. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in the respiratory tract of mice. J. Virol. 78, 3572–3577). Ribavirin given at 75mg/kg 4h prior to virus exposure and then given twice daily for 3 days beginning at day 0 was found to increase virus lung titers and extend the length of time that virus could be detected in the lungs of mice. Other IMP dehydrogenase inhibitors administered near maximum tolerated doses using the same dosing regimen as for ribavirin were found to slightly enhance virus replication in the lungs. In addition, ribavirin treatment seemed also to promote the production of pro-inflammatory cytokines 4 days after cessation of treatment, although after 3 days of treatment ribavirin inhibited pro-inflammatory cytokine production in infected mice, significantly reducing the levels of the cytokines IL-1α, interleukin-5 (IL-5), monocyte chemotactic protein-1 (MCP-1), and granulocyte-macrophage colony stimulating factor (GM-CSF). These findings suggest that ribavirin may actually contribute to the pathogenesis of SARS-CoV by prolonging and/or enhancing viral replication in the lungs. By not inhibiting viral replication in the lungs of infected mice, ribavirin treatment may have provided a continual source of stimulation for the inflammatory response thought to contribute to the pathogenesis of the infection. Our data do not support the use of ribavirin or other IMP dehydrogenase inhibitors for treating SARS infections in humans.


title: Characterization of a coronavirus I. Structural proteins: Effects of preparative conditions on the migration of protein in polyacrylamide gels

text: Abstract Coronavirus A59 possesses four size classes of structural proteins which have apparent molecular weights measured by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of 23,000 (GP23), 50,000 (VP50), 90,000 (GP90), and 180,000 (GP180). VP50 is the only structural protein which is completely unaffected by protease treatment of intact virions. This species is the most highly labeled by polar amino acids such as glutamic acid and arginine and it is probably associated with the viral nucleocapsid. GP90, GP180, and GP23 are membrane-associated proteins. However, after protease treatment of virions, only 20% of the GP23 molecule is digested, whereas all of the GP90 and GP180 are removed. GP90 and GP180 appear to comprise most of the prominent layer of characteristic projections on the external surface of the viral envelope. The major portion of GP23 is presumed to lie within the lipid envelope, protected from protease digestion. GP23 and the protease resistant portion, p∗18, exhibit anomalous behavior on SDS-PAGE. After heating to 100° in SDS the electrophoretic mobility of these polypeptides is altered and several new forms of lower mobility are produced. β-Mercaptoethanol and dithiothreitol exaggerate the effects of heating.


title: Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy

text: Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.


title: The Mongoose, the Pheasant, the Pox, and the Retrovirus

text: Paleovirology is the study of ancient viruses. The existence of a paleovirus can sometimes be detected by virtue of its accidental insertion into the germline of different animal species, which allows one to date when the virus actually existed. However, the ancient and the modern often connect, as modern viruses have unexpected origins that can be traced to ancient infections. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. REV apparently spread to poultry through a circuitous route involving the isolation of malaria parasites from a pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV. Repeated passage of this virus in poultry adapted the virus to its new host. At some point, the virus got inserted into another virus, called fowlpox virus, which has spread back into the wild. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20(th) century. These lessons of ancient and modern viruses have implications for modern human pandemics from viral reservoirs and for human interventions that may come with unintended consequences.


Renilla Luciferase as a Reporter to Assess SARS-CoV mRNA Transcription Regulation and Efficacy of ANTI-SARS-CoV Agents


title: Development of antibodies to feline IFN-γ as tools to elucidate the cellular immune responses to FeLV

text: Abstract An understanding of the nature of immune protection and the role of immune effector products such as interferon-γ (IFN-γ) in the control of infectious disease is fundamental to the rational design of effective vaccines and immunotherapeutic reagents. Murine monoclonal and sheep polyclonal antibodies (mAbs and pAbs) to feline IFN-γ (fIFN-γ) were generated firstly to facilitate further research into the role of cellular immune responses in the control of feline infectious disease, and secondly to enable evaluation of the efficacy of novel immunotherapeutic approaches. A hybridoma clone, D9, secreting IgG1 antibodies was selected for expansion and the mAbs affinity purified in vitro. Polyclonal antibodies were raised in a sheep against recombinant fIFN-γ and affinity purified. The sensitivity of the D9 mAb and the sheep anti-fIFN-γ pAb was determined using an indirect fIFN-γ enzyme-linked immunosorbent assay (ELISA) and immunoblots. These antibodies were assessed for their ability to detect the production of fIFN-γ by specific feline T cell populations ex vivo following coculture with mitogen or feline leukaemia virus (FeLV) antigens for 4 h in the presence of the protein secretion inhibitor brefeldin A (BFA). Production of fIFN-γ was evaluated using flow cytometry to simultaneously detect PE-labelled surface molecules and fluorescein isothiocyanate (FITC)-labelled intracellular fIFN-γ. Using this approach, our initial studies revealed an upregulation in virus-specific fIFN-γ-secreting CD4+T cells in the lymph nodes of FeLV latently infected cats.


title: Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases

text: Summary Background Acute exacerbation (AE) is currently established as a distinct condition with acute deterioration of respiratory status in idiopathic pulmonary fibrosis (IPF). Recently, several studies have reported that AE also occurred in interstitial pneumonias other than IPF, such as collagen vascular disease-associated interstitial pneumonia (CVD-IP). However, the incidence of AE in CVD-IP and its clinical characteristics remain to be fully determined. This study was conducted to elucidate cumulative incidence of AE in CVD-IP and its clinical features. Methods We reviewed 83 biopsy-proven CVD-IP patients, estimated cumulative incidence of AE, and examined its clinical characteristics. Results Among 83 CVD-IP patients, six patients with a mean age of 65.7 years developed AE (overall incidence, 7.2%; 1-year incidence, 1.25%). Underlying CVDs included rheumatoid arthritis (RA) (n =5; overall incidence, 20.0%) and primary Sjögren syndrome (n =1; overall incidence, 5.9%). Patients with AE showed acute respiratory deterioration with severe hypoxemia (mean PaO2/FiO2 ratio, 131). Radiologically, ground-glass opacity was superimposed on the underlying reticular abnormalities. Preexisting histological patterns included three usual interstitial pneumonia (UIP) and two non-specific interstitial pneumonia (NSIP). Five (83.3%) of six patients died of respiratory failure despite intensive therapy. Univariate Cox's proportional hazards analysis showed that age and RA diagnosis were significantly associated with AE. Multivariate Cox's proportional hazards analysis indicated that age was an independent significant factor predicting AE. Conclusions These data suggest that AE can occur in CVD-IP, and this condition is closely similar to that of IPF with poor prognosis. AE is most common in RA, and associated with higher ages.


title: Genetic, antigenic, and pathogenic characteristics of avian infectious bronchitis viruses genotypically related to 793/B in China

text: Abstract In this study, 20 infectious bronchitis virus (IBV) strains, which were genotypically related to 793/B, as assessed by an S1 gene comparison and a complete genomic sequence analysis, were isolated and identified from 2009 to 2014 in China. Phylogenetic analysis, network tree, similarity plot analysis, Recombination Detection Program 4(RDP4) and sequence comparison revealed that 12 of the 20 isolates were likely the reisolated vaccine virus. One isolate, ck/CH/LSD/110857, was shown to have originated from recombination events between H120- and 4/91-like vaccine strains that did not result in changes of antigenicity and pathogenicity. The remaining seven IBV isolates were shown to have originated from recombination events between a 4/91-like vaccine strain and a GX-LY9-like virus, which were responsible for the emergence of a novel serotype. A vaccination-challenge test found that vaccination with the 4/91 vaccine strain did not provide protection against challenge with the recombinant viruses. In addition, the results showed that the recombination events between the vaccine and field strains resulted in altered genetics, serotype, antigenicity, and pathogenicity compared with those of their deduced parental viruses. The results are important not only because this virus is of economic importance to poultry industry, but also because it is important for elucidating the origin and evolution of other coronaviruses.


title: Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

text: Abstract Objective The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n =29, 27.4%), with unilateral or bilateral consolidation (n =50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p <0.01, χ 2 test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S-OIV (H1N1).


title: Bioexclusion of diseases from dairy and beef farms: Risks of introducing infectious agents and risk reduction strategies

text: Abstract Infectious disease represents a major threat to the productivity and welfare of cattle herds throughout the world. The introduction of infectious agents into dairy and beef farms may be through direct transmission (purchased cattle, reintroduced resident cattle and contact with contiguous cattle) or indirect transmission (fomites, visitors, other species, and biological materials) and this article reviews the evidence supporting these transmission routes. In the absence of eradication programmes for many endemic infectious diseases, bioexclusion is the key management process for risk reduction. Various ameliorative bioexclusion strategies have been recommended and the evidence supporting these protocols is considered.


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title: Chapter 9 Rabies Virus as a Research Tool and Viral Vaccine Vector

text: Abstract Until recently, single-stranded negative sense RNA viruses (ssNSVs) were one of only a few important human viral pathogens, which could not be created from cDNA. The inability to manipulate their genomes hindered their detailed genetic analysis. A key paper from Conzelmann's laboratory in 1994 changed this with the publication of a method to recover rabies virus (RABV) from cDNA. This discovery not only dramatically changed the broader field of ssNSV biology but also opened a whole new avenue for studying RABV pathogenicity, developing novel RABV vaccines as well a new generation of RABV-based vaccine vectors, and creating research tools important in neuroscience such as neuronal tracing.


title: Structural Factors of the Middle East Respiratory Syndrome Coronavirus Outbreak as a Public Health Crisis in Korea and Future Response Strategies

text: The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak has originated from a failure in the national quarantine system in the Republic of Korea as most basic role of protecting the safety and lives of its citizens. Furthermore, a number of the Korean healthcare system’s weaknesses seem to have been completely exposed. The MERS-CoV outbreak can be considered a typical public health crisis in that the public was not only greatly terrorized by the actual fear of the disease, but also experienced a great impact to their daily lives, all in a short period of time. Preparedness for and an appropriate response to a public health crisis require comprehensive systematic public healthcare measures to address risks comprehensively with an all-hazards approach. Consequently, discussion regarding establishment of post-MERS-CoV improvement measures must focus on the total reform of the national quarantine system and strengthening of the public health infrastructure. In addition, the Korea Centers for Disease Control and Prevention must implement specific strategies of action including taking on the role of “control tower” in a public health emergency, training of Field Epidemic Intelligence Service officers, establishment of collaborative governance between central and local governments for infection prevention and control, strengthening the roles and capabilities of community-based public hospitals, and development of nationwide crisis communication methods.