title: Peptides with 16R in S2 protein showed broad reactions with sera against different types of infectious bronchitis viruses

text: Abstract Vaccination plays a vital role in controlling diseases caused by chicken infectious bronchitis virus (IBV). The continuously variant antigenicity of IBV limits the application of current vaccine strategies and serological diagnostic systems. S2 protein is an invariant that harbors broad neutralizing epitopes. However, little is known about the key amino acids that contribute to the broad-spectrum S2 epitopes. In this study, we aimed to elucidate the specific amino acids contributing to S2 epitopes. Site mutagenesis and peptide-based enzyme-linked immunosorbent assays (ELISAs) showed that 16R in S2 protein was a key amino acid mediating the antigenicity of S2 protein. S2-derived peptides with 16R, but not those with 16 K, could react with sera against different types of IBVs. Notably, a commercial ELISA kit for detection of antibodies against IBV did not react with sera against all types of IBVs. Taken together, these data demonstrated that S2-derived peptides with 16R could be used as novel marker-based antigens for developing both broad-spectrum vaccines and serological diagnostic kits to control IBV.


title: Pathogen Security-Help or Hindrance?

text: Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.


title: Spread of SARS-CoV-2 in the Icelandic Population

text: BACKGROUND: During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population. METHODS: We targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons. We sequenced SARS-CoV-2 from 643 samples. RESULTS: As of April 4, a total of 1221 of 9199 persons (13.3%) who were recruited for targeted testing had positive results for infection with SARS-CoV-2. Of those tested in the general population, 87 (0.8%) in the open-invitation screening and 13 (0.6%) in the random-population screening tested positive for the virus. In total, 6% of the population was screened. Most persons in the targeted-testing group who received positive tests early in the study had recently traveled internationally, in contrast to those who tested positive later in the study. Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older. Fewer females than males received positive results both in targeted testing (11.0% vs. 16.7%) and in population screening (0.6% vs. 0.9%). The haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time. The percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening. CONCLUSIONS: In a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts. (Funded by deCODE Genetics–Amgen.)


title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA

text: BACKGROUND: Infectious cDNA clones are a prerequisite for directed genetic manipulation of RNA viruses. Here, a strategy to facilitate manipulation and rescue of classical swine fever viruses (CSFVs) from full-length cDNAs present within bacterial artificial chromosomes (BACs) is described. This strategy allows manipulation of viral cDNA by targeted recombination-mediated mutagenesis within bacteria. RESULTS: A new CSFV-BAC (pBeloR26) derived from the Riems vaccine strain has been constructed and subsequently modified in the E2 coding sequence, using the targeted recombination strategy to enable rescue of chimeric pestiviruses (vR26_E2gif and vR26_TAV) with potential as new marker vaccine candidates. Sequencing of the BACs revealed a high genetic stability during passages within bacteria. The complete genome sequences of rescued viruses, after extensive passages in mammalian cells showed that modifications in the E2 protein coding sequence were stably maintained. A single amino acid substitution (D3431G) in the RNA dependent RNA polymerase was observed in the rescued viruses vR26_E2gif and vR26, which was reversion to the parental Riems sequence. CONCLUSIONS: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses.


Health Care–Associated Infections (HAIs)


title: Acute hepatic failure in IFN-γ-deficient BALB/c mice after murine coronavirus infection

text: Abstract We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) persists in interferon-γ (IFN-γ)-deficient C57BL/6 (B6-GKO) mice and results in subacute fatal peritonitis, which bears a resemblance to feline infectious peritonitis. To examine the role of other host factors in MHV infection in mice, IFN-γ-deficient mice with a BALB/c background (BALB-GKO) were infected intraperitoneally with MHV and compared with B6-GKO mice. In contrast to B6-GKO mice, BALB-GKO mice died within 1 week due to acute hepatic failure. The viral titer of the liver in BALB-GKO mice was significantly higher than that in B6-GKO mice. All hepatocytes in BALB-GKO mice were necrotic at 5 days post-infection, which was clearly distinct from large but limited lesion in the liver from infected B6-GKO mice. The serum alanine aminotransferase activity of infected BALB-GKO mice were higher than that of B6-GKO mice and was paralleled with the severity of the pathological changes and viral titers in infected mice. Administration of exogenous IFN-γ to BALB-GKO partially inhibited the acute death. These results indicate that BALB-GKO and B6-GKO mice clearly show different diseases following MHV infection, although wild type counterparts of both mice apparently showed the same clinical course after MHV infection.


title: Changing the narrative on fisheries subsidies reform: Enabling transitions to achieve SDG 14.6 and beyond

text: Abstract The World Trade Organization (WTO) is in the final stages of negotiating an agreement to prohibit harmful fisheries subsidies, thereby achieving UN Sustainable Development Goal (SDG) 14.6. An effective agreement should be viewed as an opportunity for nations to proactively transition towards sustainable and equitable fisheries and pave the path for other SDGs. Supporting fishers does not require harmful subsidies, and we provide evidence-based options for reform that highlight equity needs while reducing environmental harm. Subsidy reforms need clear goals, co-design, transparency, and fair implementation. An agreement on SDG 14.6 could be a turning point for the oceans and for the well-being of those that depend on the oceans for livelihoods and nutrition. Responsible seafood production will require international cooperation not only at WTO, but among governments, fisher organizations, civil society, and the wider public.


title: The protean prion protein

text: The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrP(C)) and the scrapie conformation (PrP(Sc)). PrP(C) features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with β-strand propensity has been identified within it. The PrP(Sc) conformation is very rare and has the characteristics of an amyloid. Furthermore, PrP(Sc) is a prion, i.e., it is infectious. This involves 2 steps: (1) PrP(Sc) can template PrP(C) and coerce it to adopt the PrP(Sc) conformation and (2) PrP(Sc) can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrP(Sc) is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology, Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.


title: Human iPSC-Derived Cardiomyocytes , are Susceptible to SARS-CoV-2 Infection

text: Summary Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA-sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.


title: A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin

text: Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.


title: Micro- and nanotechnology for viral detection

text: Since the identification of viruses at the start of the 20th century, detecting their presence has presented great challenges. In the past two decades, there has been significant progress in viral detection methods for clinical diagnosis and environmental monitoring. The earliest advances were in molecular biology and imaging techniques. Advances in microfabrication and nanotechnology have now begun to play an important role in viral detection, and improving the detection limit, operational simplicity, and cost-effectiveness of viral diagnostics. Here we provide an overview of recent advances, focusing especially on advances in simple, device-based approaches for viral detection.


title: Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series

text: BACKGROUND: Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited. CASE PRESENTATION: We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections. CONCLUSIONS: IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.


title: Stress, anxiety, and depression in people aged over 60 in the COVID-19 outbreak in a sample collected in Northern Spain.

text: OBJECTIVE: This study examines the levels of stress, anxiety, and depression in people over 60 years of age at the time of the COVID-19 outbreak. DESIGN: The study used an exploratory-descriptive cross-sectional methodology. The resulting responses were analyzed using SPSS v.25 PARTICIPANTS: Participants (N=210) were aged 60 years and above. SETTING: The study was carried out in the Basque Country (North of Spain) MEASUREMENTS: Stress, anxiety and depression were measured using the Anxiety and Stress Scale - 21 (DASS-21) RESULTS: Most of the participants did not report levels of stress, anxiety, and depression. Among participants age 66 and above and those with chronic illness, a proportion reported experiencing one, two or all three of these symptoms


title: Building core capacities at the designated points of entry according to the International Health Regulations 2005: a review of the progress and prospects in Taiwan

text: BACKGROUND: As designated points of entry (PoEs) play a critical role in preventing the transmission of international public health risks, huge efforts have been invested in Taiwan to improve the core capacities specified in the International Health Regulations 2005 (IHR 2005). This article reviews how Taiwan strengthened the core capacities at the Taoyuan International Airport (TIA) and the Port of Kaohsiung (PoK) by applying a new, practicable model. DESIGN: An IHR PoE program was initiated for implementing the IHR core capacities at designated PoEs. The main methods of this program were 1) identifying the designated PoEs according to the pre-determined criteria, 2) identifying the competent authority for each health measure, 3) building a close collaborative relationship between stakeholders from the central and PoE level, 4) designing three stages of systematic assessment using the assessment tool published by the World Health Organization (WHO), and 5) undertaking action plans targeting the gaps identified by the assessments. RESULTS: Results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed a continuous progressive trend at the TIA (86, 91, and 100%, respectively), and at the PoK (77, 97, and 99.9%, respectively). The results of the follow-up external assessment indicated that both these designated PoEs already conformed to the IHR requirements. These achievements were highly associated with strong collaboration, continuous empowerment, efficient resource integration, and sustained commitments. CONCLUSIONS: Considering that many countries had requested for an extension on the deadline to fulfill the IHR 2005 core capacity requirements, Taiwan's experiences can be a source of learning for countries striving to fully implement these requirements. Further, in order to broaden the scope of public health protection into promoting global security, Taiwan will keep its commitments on multisectoral cooperation, human resource capacity building, and maintaining routine and emergency capacities.


Urgent digestive surgery, a collateral victim of the Covid-19 crisis?


title: Prevention of Medical Events During Air Travel: A Narrative Review

text: Abstract Prior to traveling, and when seeking medical pretravel advice, patients consult their personal physicians. Inflight medical issues are estimated to occur up to 350 times per day worldwide (1/14,000-40,000 passengers). Specific characteristics of the air cabin environment are associated with hypoxia and the expansion of trapped gases into body cavities, which can lead to harm. The most frequent medical events during air travel include abdominal pain; ear, nose, and throat pathologies; psychiatric disorders; and life-threatening events such as acute respiratory failure or cardiac arrest. Physicians need to be aware of the management of these conditions in this unusual setting. Chronic respiratory and cardiovascular diseases are common and are at increased risk of acute exacerbation. Physicians must be trained in these conditions and inform their patients about their prevention.


title: Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study

text: BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18–75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO(2)]/fractional concentration of oxygen in inspired air [FiO(2)]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m(2) (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO(2)/FiO(2) ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9–65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO(2)/FiO(2) ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 10(3)/μL [101·9] vs 319·8 × 10(3)/μL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.


title: Who Regulates Whom? An Overview of RNA Granules and Viral Infections

text: After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs).


Herpes zoster as a potential complication of coronavirus disease 2019


title: Who goes to a library for cancer information in the e-health era? A secondary data analysis of the Health Information National Trends Survey (HINTS)

text: Abstract This study identifies characteristics of Americans who chose the library as their primary cancer information source over the Internet by examining demographic characteristics, online use experience, concerns of information quality, and perceptions of cancer information seeking. A secondary data analysis is conducted using the Health Information National Trends Survey (HINTS) of the National Cancer Institute (NCI). Findings reveal that people who are more likely to choose the library are, compared to their Internet counterparts, people who lack online experience, are distrustful of online cancer information, and are more aware of cancer sources. However, they are not necessarily more adept cancer information seekers and do not have a greater expectation of getting quality information from the library. These findings suggest how the library plays its role as an information source for cancer information consumers in the e-health environment. Implications of the findings are discussed in a way that libraries could invest their efforts to reduce the digital health divide and to advance consumer health information literacy.


title: Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

text: To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.


title: Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

text: The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.


title: Antiviral Properties of ISG15

text: The type I interferon system plays a critical role in limiting the spread of viral infection. Viruses induce the production of interferon (IFN), which after binding to the IFN-α/β receptor (IFNAR), and triggering of the JAK/STAT signaling cascade, results in the induction of interferon-stimulated genes (ISGs). These ISGs function to inhibit viral replication and to regulate the host immune response. Among these ISGs, the ubiquitin-like molecule, ISG15, is one of the most strongly induced proteins. Similar to ubiquitin, through an IFN induced conjugation cascade, ISG15 is covalently linked to a variety of cellular proteins, suggesting regulation of different cellular processes. Studies performed over the past several years have shown that ISG15 plays a central role in the host’s antiviral response against many viruses. Mice lacking ISG15 display increased susceptibility to multiple viruses. Furthermore, several viruses have developed immune evasion strategies that directly target the ISG15 pathway. Work is now underway to determine the mechanism by which ISG15 functions as an antiviral molecule, such that therapies targeting this pathway can be developed in the future.


title: A successful general fluid-to-fluid similarity theory for heat transfer at supercritical pressure

text: The present paper introduces a successful and general fluid-to-fluid similarity theory for heat transfer to fluids at supercritical pressure, having a high degree of universality. This work shortly follows the recent publication of a “local” successful similarity theory developed for fluids at supercritical pressures in a range of conditions in which the values of their molecular Prandtl number were quantitatively similar, extending its conclusions to the case of different molecular Prandtl numbers. The reason why this further step requested a short time to be elaborated is due to recognising that previous work by the Authors had actually already solved the related problems, though in a slightly different way, now interpreted in a more significant frame owing to a better problem understanding. The present similarity theory is based on first ideas developed more than one and a half decade ago by one of the authors, while addressing flow stability of supercritical fluids in heated channels, which encountered immediate problems to be applied in a straightforward way to heat transfer. These ideas were revised and considerably improved during the PhD thesis of the other author, also overcoming a sort of prejudicial assumption that finally resulted to limit their applicability. More recently, published DNS data triggered further reflections on the role of the Prandtl number, leading to the mentioned “local” form of the successful similarity theory. This led to the present step, by just recognising that the mentioned PhD thesis had already proposed a sufficient rationale to extend this local interpretation to a broader range of conditions. The rather convincing results presented herein, obtained making use of RANS CFD analyses with four different fluids, demonstrate the interesting capabilities of this final form of the theory. The establishment of an effective set of dimensionless numbers for heat transfer problems is hoped to pave the way for the development of the still lacking successful engineering heat transfer correlations for supercritical pressure fluids. It further calls for dedicated experiments needed to confirm the suitability of the present theory beyond any reasonable doubt.


title: Clinical Vignettes: Donor-Derived Infections

text: Patients undergoing solid organ transplantation (SOT) may acquire infections from the transplanted organ. Routine screening for common infections are an established part of the pretransplant evaluation of donors and recipients. Likewise, strategies exist for prophylaxis and surveillance for common donorassociated infections including hepatitis B, CMV and EBV. However, despite advances in diagnostic testing to evaluate the infectious risk of donors, unanticipated transmission of pathogens occurs, particularly when donors are asymptomatic or have subtle or unusual manifestations of a transmissible Infection. Infectious diseases (ID) providers play an integral role in donor and recipient risk assessment and can advise transplant centers on organ utilization and guide evaluation and management of the SOT recipient. Consideration of the donor cause of death and preceding clinical syndromes are important for characterizing the potential risk for recipient infection. This allows a more accurate analysis of the risk: benefit of accepting a life-saving organ and risk of infection. ID providers and transplant teams should work closely with organ procurement organizations (OPOs) to solicit additional donor information when a donor-derived infection is suspected so that reporting can be facilitated to ensure communication with the care-teams of other organ recipients from the same donors. National advisory committees work closely with federal agencies to provide oversight, guide policy development, and assess outcomes to assist with the prevention and management of donor-transmitted disease through organ transplantation. The clinical vignettes in this review highlight some of the complexities in the evaluation of potential donor transmission.


title: Global mapping of cholera Vibrio and outbreaks in the Pre-Millennium Development Goals (MDG)/Sustainable Development Goals (SDG) and MDGs/SDGs era of 1990–2019

text: Vibrio species and cholera outbreak yet remain a frequent health emergency despite progress made in integrated implementation of the MDGs/SDGs/WASH worldwide. Hence, this study aimed at appraising the impacts of MDGs/SDGs/WASH campaigns on the mitigation of cholera outbreak and associated consequences. The study mapped scientific production related to Vibrio outbreak from 1990 to 2019, identified trend, institutional/international concerted efforts toward outbreak research/response and gaps for future preparedness. Relevant documents were identified from the Web of Science database using an optimised title-field specific search Boolean that accommodated all pre-set inclusion criteria for the study. A total of 901 documents were identified including 869 available abstracts were retrieved for content-review of human incidence cases, mortality, culprit Vibrio species, strains, and biotypes. Explanatory analysis showed that the trend of outbreak documents approximately increased in 6th order quadratic relationship (R(2) = 0.7948) from 1990 to 2019 with an annual growth rate of 3.21% and a mean value of 30.0 ± 18.0 per year. Other details revealed an increased and undulating case report/mortality rate of cholera outbreaks especially in the MDGs/SDGs era. Decadal comparison of Vibrio outbreak during the period showed significant variation in documents distribution (Kruskal-Wallis p = 0.00077). based on countries’ efforts, the USA, ranked first in terms of article numbers (191), publication frequency (24.6(%) and total citations (5962). Four prevailing conceptual frameworks were identified in the outbreak documents with global community interest revealed as the largest topical coverage. All conceptual frameworks consisted in Vibrio characterisation, methodology-related, intervention-related, geographic-related concepts and some replete with health and climate-change depicting concepts. Also, the study observed high mortality in Vibrio outbreaks during 1990–1999 (29080 deaths), and 2010–2019 (386606 deaths) compared to 2000–2009 (7705 deaths) (Kruskal-Wallis, p < 0.05). High number of outbreaks due to V. cholerae and V. parahaemolyticus and a limited outbreaks attributed to emerging strains. In conclusion, vibrio outbreak has not lived up to various investment put into its control from various programme evolutions. The broad spectrum Vibrio vaccines that could cater for outbreak caused by common and emerging strains is inevitable and a significant thrust for future research.


title: In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus

text: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.


title: Estimation of Unreported Novel Coronavirus (SARS-CoV-2) Infections from Reported Deaths: A Susceptible–Exposed–Infectious–Recovered–Dead Model

text: In the midst of the novel coronavirus (SARS-CoV-2) epidemic, examining reported case data could lead to biased speculations and conclusions. Indeed, estimation of unreported infections is crucial for a better understanding of the current emergency in China and in other countries. In this study, we aimed to estimate the unreported number of infections in China prior to the 23 January 2020 restrictions. To do this, we developed a Susceptible–Exposed–Infectious–Recovered–Dead (SEIRD) model that estimated unreported infections from the reported number of deaths. Our approach relied on the fact that observed deaths were less likely to be affected by ascertainment biases than reported infections. Interestingly, we estimated that the basic reproductive number (R(0)) was 2.43 (95%CI = 2.42–2.44) at the beginning of the epidemic and that 92.9% (95%CI = 92.5%–93.1%) of total cases were not reported. Similarly, the proportion of unreported new infections by day ranged from 52.1% to 100%, with a total of 91.8% (95%CI = 91.6%–92.1%) of infections going unreported. Agreement between our estimates and those from previous studies proves that our approach is reliable for estimating the prevalence and incidence of undocumented SARS-CoV-2 infections. Once it has been tested on Chinese data, our model could be applied to other countries with different surveillance and testing policies.


title: Principles of and Advances in Immunoglobulin Replacement Therapy for Primary Immunodeficiency

text: During the last 2 decades, the continued development and the large-scale production of polyclonal immune serum globulin (ISG) preparations with improved safety and tolerability profiles have allowed treatment to focus on quality of life and long-term freedom from the complications of primary immune deficiency disease, rather than just on freedom from severe acute infections and survival. Available ISG preparations allow routine therapy by a variety of routes and regimens that can be tailored to suit individual patients. Continued vigilance is required, however, because problems with emerging diseases, and the costs and availability of ISG are likely to present continuing challenges.


title: Multiple viral respiratory pathogens in children with bronchiolitis

text: AIM: The aim of the study was to describe the frequency of viral pathogens and relative frequency of co-infections in nasal specimens obtained from young children with bronchiolitis receiving care at a children’s hospital. METHODS: We conducted a study of nasal wash specimens using real-time PCR and fluorescent-antibody assay results from children less than two with an ICD-9-CM code for bronchiolitis. All specimens were collected for clinical care at Children’s Hospital in Seattle, WA, USA, during the respiratory season from October 2003 to April 2004. RESULTS: Viruses were detected in 168 (93%) of the 180 children with bronchiolitis. A single virus was identified in 127 (71%) children and multiple viruses in 41 (23%). Respiratory syncytial virus (RSV) was the most common virus detected (77%), followed by adenovirus (15%), human metapneumovirus (11%), coronavirus (8%), parainfluenza (6%) and influenza (1%). Of the 139 samples with RSV detected, 34 (24%) were co-infected with another viral pathogen. CONCLUSION: Molecular diagnostic techniques identified a high frequency of viruses and viral co-infections among children evaluated for bronchiolitis. Further study of the role of viral pathogens other than RSV and co-infections with RSV in children with bronchiolitis appears warranted.


title: Hepatic complications of COVID‐19 and its treatment

text: COVID‐19 is highly contagious and has a variety of clinical manifestations, it can affect a number of other organs in addition to the lungs, and liver injury may occur. SARS‐CoV‐2 can cause liver injury through systemic inflammatory response syndrome (SIRS), cytokine storms, ischemia‐reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via ACE2. Clinical studies have found that liver injury in COVID‐19 patients mainly manifests as abnormal liver biochemical indicators, but there have been no reports of liver failure caused by this disease. The number of COVID‐19 patients with liver injury is increasing, and the incidence of liver injury in COVID‐19 patients with severe disease are higher than in patients with mild disease. Liver injury may be a risk factor for progresses and worsens in patients with COVID‐19, and it is necessary to pay attention to the occurrence of liver injury in the diagnosis and treatment of COVID‐19. This article is protected by copyright. All rights reserved.


title: Antiviral activity of the high-molecular-weight plant polysaccharides (Panavir®)()

text: This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.


title: Novel coronavirus disease 2019 (COVID‐19) and neurodegenerative disorders

text: During the last few months, the whole humanity is experiencing largest and most severe sudden influx of COVID‐19 outbreak caused by the novel coronavirus (CoV) originated from Wuhan, China. According to the WHO reports, total 3 862 676 positive cases and 265 961 deaths have been recorded worldwide due to COVID‐19 infection as of May 9, 2020. CoVs are a large family of viruses (enveloped, single‐stranded RNA viruses), which includes severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome‐related coronavirus (MERS‐CoV). New SARS CoV2 is the members of Betacoronavirus genus. These viruses cause infections in bats, camels and humans, and a few other associated species. Despite many neurologic complications associated with SARS‐CoV‐2 infection, it is still unclear whether these symptoms results from direct neural injury or due to some other reason. Currently, it appears that most of the neurological symptoms of COVID‐19 are nonspecific and secondary to the systemic illness. A single case of acute hemorrhagic necrotizing encephalopathy has been reported. SARS‐CoV‐2 associated Guillain‐Barré syndrome is an atypical case. Till today, no convincing evidence is available to confirm that the SARS‐CoV‐2 virus directly affects nerves system in humans. However, postinfection surveillance will be necessary to identify the possible post‐COVID‐19 neurologic syndromes.


title: Older Adults’ Technology Use and its Association with Health and Depressive Symptoms: Findings from the 2011 National Health and Aging Trends Study

text: Abstract Background Information and communication technology (ICT) provides older adults with access to information and resources that benefit their health. Purpose To explore ICT use among older adults and examine the influence of information technology (IT), communication technology (CT), or ICT use on older adults’ self-rated health status and depressive symptoms. Method A sample of community-dwelling Medicare beneficiaries aged 65 and older in the U.S. (N = 4,976) from the 2011 National Health and Aging Trends Study. Findings Older adults who embraced ICT and used this technology for a variety of purposes were more likely to report better health status, and were less likely to experience major depressive symptoms than non-users. Discussion In accordance with the Health Information Technology for Economic and Clinical Health Act (HITECH Act), nursing professional can play an important role by responding to older adults’ diverse technology preferences and effectively incorporating them into nursing practice.


title: Reduced dynamic range of antiviral innate immune responses in aging

text: Abstract The worldwide population aged≥65years is increasing and the average life span is expected to increase another 10years by 2050. This extended lifespan is associated with a progressive decline in immune function and a paradoxical state of low-grade, chronic inflammation that may contribute to susceptibility to viral infection, and reduced responses to vaccination. Here we review the effects of aging on innate immune responses to viral pathogens including elements of recognition, signaling, and production of inflammatory mediators. We specifically focus on age-related changes in key pattern recognition receptor signaling pathways, converging on altered cytokine responses, including a notable impairment of antiviral interferon responses. We highlight an emergent change in innate immunity that arises during aging – the dampening of the dynamic range of responses to multiple sources of stimulation – which may underlie reduced efficiency of immune responses in aging.


title: Crisis in New York City

text: The coronavirus outbreak has hit the city hard and doctors are racing to treat the rapidly increasing cases, reports Carrie Arnold


title: COVID-19 related coagulopathy: A distinct entity?

text: The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy.


title: The Rise and Impact of COVID-19 in India

text: The coronavirus disease (COVID-19) pandemic, which originated in the city of Wuhan, China, has quickly spread to various countries, with many cases having been reported worldwide. As of May 8th, 2020, in India, 56,342 positive cases have been reported. India, with a population of more than 1.34 billion—the second largest population in the world—will have difficulty in controlling the transmission of severe acute respiratory syndrome coronavirus 2 among its population. Multiple strategies would be highly necessary to handle the current outbreak; these include computational modeling, statistical tools, and quantitative analyses to control the spread as well as the rapid development of a new treatment. The Ministry of Health and Family Welfare of India has raised awareness about the recent outbreak and has taken necessary actions to control the spread of COVID-19. The central and state governments are taking several measures and formulating several wartime protocols to achieve this goal. Moreover, the Indian government implemented a 55-days lockdown throughout the country that started on March 25th, 2020, to reduce the transmission of the virus. This outbreak is inextricably linked to the economy of the nation, as it has dramatically impeded industrial sectors because people worldwide are currently cautious about engaging in business in the affected regions.


title: Correlation Between UpToDate Searches and Reported Cases of Middle East Respiratory Syndrome During Outbreaks in Saudi Arabia

text: Background. UpToDate is an online clinical decision support resource that is used extensively by clinicians around the world. Digital surveillance techniques have shown promise to aid with the detection and monitoring of infectious disease outbreaks. We sought to determine whether UpToDate searches for Middle East respiratory syndrome (MERS) could be used to detect and monitor MERS outbreaks in Saudi Arabia. Methods. We analyzed daily searches related to MERS in Jeddah and Riyadh, Saudi Arabia during 3 outbreaks in these cities in 2014 and 2015 and compared them with reported cases during the same periods. We also compared UpToDate MERS searches in the affected cities to those in a composite of 4 negative control cities for the 2 outbreaks in 2014. Results. UpToDate MERS searches during all 3 MERS outbreaks in Saudi Arabia showed a correlation to reported cases. In addition, UpToDate MERS search volume in Jeddah and Riyadh during the outbreak periods in 2014 was significantly higher than the concurrent search volume in the 4 negative control cities. In contrast, during the baseline periods, there was no difference between UpToDate searches for MERS in the affected cities compared with the negative control cities. Conclusions. UpToDate search activity seems to be useful for detecting and monitoring outbreaks of MERS in Saudi Arabia.


COVID-19: Outcomes for trauma-impacted nurses and nursing students


title: Aerosol influenza transmission risk contours: A study of humid tropics versus winter temperate zone

text: BACKGROUND: In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft. RESULTS: An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk. CONCLUSION: Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza epidemiology in addition to seasonality in temperate climates.


title: Using Information Technology to Manage the COVID-19 Pandemic: Development of a Technical Framework Based on Practical Experience in China

text: BACKGROUND: The coronavirus disease (COVID-19) epidemic poses an enormous challenge to the global health system, and governments have taken active preventive and control measures. The health informatics community in China has actively taken action to leverage health information technologies for epidemic monitoring, detection, early warning, prevention and control, and other tasks. OBJECTIVE: The aim of this study was to develop a technical framework to respond to the COVID-19 epidemic from a health informatics perspective. METHODS: In this study, we collected health information technology–related information to understand the actions taken by the health informatics community in China during the COVID-19 outbreak and developed a health information technology framework for epidemic response based on health information technology–related measures and methods. RESULTS: Based on the framework, we review specific health information technology practices for managing the outbreak in China, describe the highlights of their application in detail, and discuss critical issues to consider when using health information technology. Technologies employed include mobile and web-based services such as Internet hospitals and Wechat, big data analyses (including digital contact tracing through QR codes or epidemic prediction), cloud computing, Internet of things, Artificial Intelligence (including the use of drones, robots, and intelligent diagnoses), 5G telemedicine, and clinical information systems to facilitate clinical management for COVID-19. CONCLUSIONS: Practical experience in China shows that health information technologies play a pivotal role in responding to the COVID-19 epidemic.


title: A systematic approach to virus–virus interactions

text: Abstract A virus–virus interaction is a measurable difference in the course of infection of one virus as a result of a concurrent or prior infection by a different species or strain of virus. Many such interactions have been discovered by chance, yet they have rarely been studied systematically. Increasing evidence suggests that virus–virus interactions are common and may be critical to understanding viral pathogenesis in natural hosts. In this review we propose a system for classifying virus–virus interactions by organizing them into three main categories: (1) direct interactions of viral genes or gene products, (2) indirect interactions that result from alterations in the host environment, and (3) immunological interactions. We have so far identified 15 subtypes of interaction and assigned each to one of these categories. It is anticipated that this framework will provide for a more systematic approach to investigating virus–virus interactions, both at the cellular and organismal levels.


title: Dramatic decrease of laboratory‐confirmed influenza A after school closure in response to COVID‐19

text: The novelty of the coronavirus disease 2019 (COVID-19) has led some researchers to use influenza models and changes in influenza activity to infer the impact of social distancing measures to mitigate the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 This article is protected by copyright. All rights reserved.


title: Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks

text: Abstract In the case of pandemic crisis situations, a crucial lack of protective material such as protective face masks for healthcare professionals can occur. A proof of concept (PoC) and prototype are presented, demonstrating a reusable custom-made three-dimensionally (3D) printed face mask based on materials and techniques (3D imaging and 3D printing) with global availability. The individualized 3D protective face mask consists of two 3D-printed reusable polyamide composite components (a face mask and a filter membrane support) and two disposable components (a head fixation band and a filter membrane). Computer-aided design (CAD) was used to produce the reusable components of the 3D face mask based on individual facial scans, which were acquired using a new-generation smartphone with two cameras and a face scanning application. 3D modelling can easily be done by CAD designers worldwide with free download software. The disposable non-woven melt-blown filter membrane is globally available from industrial manufacturers producing FFP2/3 protective masks for painting, construction, agriculture, and the textile industry. Easily available Velcro fasteners were used as a disposable head fixation band. A cleaning and disinfection protocol is proposed. Leakage and virological testing of the reusable components of the 3D face mask, following one or several disinfection cycles, has not yet been performed and is essential prior to its use in real-life situations. This PoC should allow the reader to consider making and/or virologically testing the described custom-made 3D-printed face masks worldwide. The surface tessellation language (STL) format of the original virtual templates of the two reusable components described in this paper can be downloaded free of charge using the hyperlink ( Supplementary Material online).


title: Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation

text: Objective To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. Design Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013. Setting Wuxi, Eastern China. Participants Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. Main outcomes measures Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. Results The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. Conclusions The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.


title: Nanomaterials and nanocomposite applications in veterinary medicine

text: Nowadays, nanotechnology has made huge, significant advancements in biotechnology and biomedicine related to human and animal science, including increasing health safety, production, and the elevation of national income. There are various fields of nanomaterial applications in veterinary medicine such as efficient diagnostic and therapeutic tools, drug delivery, animal nutrition, breeding and reproduction, and valuable additives. Additional benefits include the detection of pathogens, protein, biological molecules, antimicrobial agents, feeding additives, nutrient delivery, and reproductive aids. There are many nanomaterials and nanocomposites that can be used in nanomedicine such as metal nanoparticles, liposomes, carbon nanotubes, and quantum dots. In the near future, nanotechnology research will have the ability to produce novel tools for improving animal health and production. Therefore, this chapter was undertaken to spotlight novel methods created by nanotechnology for application in the improvement of animal health and production. In addition, the toxicity of nanomaterials is fully discussed to avoid the suspected health hazards of toxicity for animal health safety.


title: Clinical and surgical consequences of the COVID-19 pandemic for patients with pediatric urological problems Statement of the EAU guidelines panel for paediatric urology, March 30 2020

text: Summary The COVID-19-pandemic forces hospitals to reorganize into a dual patient flow system. Healthcare professionals are forced to make decisions in patient prioritization throughout specialties. Most pediatric urology pathologies do not require immediate or urgent care, however, delay may compromise future renal function or fertility. Contact with patients and parents, either physical in safe conditions or by (video)telephone must continue. The Paediatric-Urology-Guidelines-panel of the EAU proposes recommendations on prioritization of care. Pediatric-Urology program directors must ensure education, safety and attention for mental health of staff. Upon resumption of care, adequate prioritization must ensure minimal impact on outcome.


title: Amoxicillin–clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial

text: BACKGROUND: Although amoxicillin–clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis. METHODS: We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1–19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin–clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of −20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897). FINDINGS: We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin–clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin–clavulanate group. The risk difference showed non-inferiority (−0·3%, 95% CI −11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin–clavulanate group than in the azithromycin group (median 10 days [IQR 6–15] vs 14 days [8–16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin–clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5). INTERPRETATION: By 21 days of treatment, azithromycin is non-inferior to amoxicillin–clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance. FUNDING: Australian National Health and Medical Research Council.


title: Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

text: Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.


title: Sinus Node Dysfunction in a Young Patient with COVID-19

text: Abstract A 34-year-old man was admitted with acute lung injury and COVID-19 pneumonia. In intensive care unit, he experienced episodes of prolonged asystole accompanied by hypotension without loss of consciousness. Once reversible causes were excluded, symptoms were related to dysfunction of the sinus node and patient underwent PM implantation.


The impact of viral respiratory infections in the first year post-transplant period of pediatric hematopoietic stem cell transplant (HSCT) recipients


title: Microbiology of otitis media: A moving target

text: Abstract The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal commensal flora. This respiratory ecosystem undergoes various selective pressures, such as antibiotic consumption and vaccine use. Socio-economic conditions also influence the bacterial composition of the nasopharynx. Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM worldwide. This paper will discuss the causes and consequences of recent shifts in the underlying microbiology of AOM.


title: A Heterospecific Leucine Zipper Tetramer

text: Summary Protein-protein interactions dictate the assembly of the macromolecular complexes essential for functional networks and cellular behavior. Elucidating principles of molecular recognition governing important interfaces such as coiled coils is a challenging goal for structural and systems biology. We report here that two valine-containing mutants of the GCN4 leucine zipper that fold individually as four-stranded coiled coils associate preferentially in mixtures to form an antiparallel, heterotetrameric structure. X-ray crystallographic analysis reveals that the coinciding hydrophobic interfaces of the hetero- and homotetramers differ in detail, explaining their partnering and structural specificity. Equilibrium disulfide exchange and thermal denaturation experiments show that the 50-fold preference for heterospecificity results from a combination of preferential packing and hydrophobicity. The extent of preference is sensitive to the side chains comprising the interface. Thus, heterotypic versus homotypic interaction specificity in coiled coils reflects a delicate balance in complementarity of shape and chemistry of the participating side chains.


title: Physiologic and other effects and compliance with long-term respirator use among medical intensive care unit nurses

text: BACKGROUND: Long-term use of respiratory protection may be necessary, but compliance may be low, and physiologic effects have not been well evaluated. METHODS: Ten nurses participated; physiologic effects, subjective symptoms, and compliance with wearing an N95 alone or with a surgical mask overlay were assessed. Longitudinal analysis based on multivariate linear regression models assessed changes in outcome variables (CO(2), O(2), heart rate, perceived comfort items, compliance measures, and others). Analyses compared changes over time, and compared wearing only an N95 to wearing an N95 with a surgical mask overlay. RESULTS: Most nurses (90%, n = 9) tolerated wearing respiratory protection for two 12-hour shifts. CO(2) levels increased significantly compared with baseline measures, especially when comparing an N95 with a surgical mask to only an N95, but changes were not clinically relevant. Perceived exertion; perceived shortness of air; and complaints of headache, lightheadedness, and difficulty communicating also increased over time. Almost one-quarter (22%) of respirator removals were due to reported discomfort. N95 adjustments increased over time, but other compliance measures did not vary by time. Compliance increased on day 2, except for adjustments, touching under the N95, and eye touches. CONCLUSION: Long-term use of respiratory protection did not result in any clinically relevant physiologic burden for health care personnel, although many subjective symptoms were reported. N95 compliance was fairly high.


Asthma und Covid-19


title: From Hippocrates to HIPAA: Privacy and confidentiality in Emergency Medicine—Part I: Conceptual, moral, and legal foundations

text: Respect for patient privacy and confidentiality is an ancient and a contemporary professional responsibility of physicians. Carrying out this responsibility may be more challenging and more important in the emergency department than in many other clinical settings. Part I of this 2-part article outlines the basic concepts of privacy and confidentiality, reviews the moral and legal foundations and limits of these concepts, and highlights the new federal privacy regulations implemented under the Health Insurance Portability and Accountability Act of 1996. Part II of the article examines specific privacy and confidentiality issues commonly encountered in the ED.


Circulating endothelial cells in COVID‐19


title: Gene duplication and phylogeography of North American members of the Hart Park serogroup of avian rhabdoviruses

text: Abstract Flanders virus (FLAV) and Hart Park virus (HPV) are rhabdoviruses that circulate in mosquito–bird cycles in the eastern and western United States, respectively, and constitute the only two North American representatives of the Hart Park serogroup. Previously, it was suggested that FLAV is unique among the rhabdoviruses in that it contains two pseudogenes located between the P and M genes, while the cognate sequence for HPV has been lacking. Herein, we demonstrate that FLAV and HPV do not contain pseudogenes in this region, but encode three small functional proteins designated as U1–U3 that apparently arose by gene duplication. To further investigate the U1–U3 region, we conducted the first large-scale evolutionary analysis of a member of the Hart Park serogroup by analyzing over 100 spatially and temporally distinct FLAV isolates. Our phylogeographic analysis demonstrates that although FLAV appears to be slowly evolving, phylogenetically divergent lineages co-circulate sympatrically.


title: Seroprevalence of SARS Coronavirus Among Residents Near a Hospital with a Nosocomial Outbreak

text: Background/Purpose An epidemic of severe acute respiratory syndrome (SARS) occurred in Taiwan from April to July 2003. A nosocomial outbreak of SARS occurred at Kaohsiung Chang Gung Memorial Hospital (CGMH) in May 2003. The purpose of our study was to survey the prevalence of the SARS coronavirus (CoV) in a community adjacent to Kaohsiung CGMH and collect demographic data, including basic information about health status, household, and possible risk factors for SARS-CoV infection. Methods We randomly recruited 1030 persons living in three precincts adjacent to Kaohsiung CGMH. For all subjects, we collected demographic data and measured the seroprevalence of the SARS-CoV with an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IFA). Results The ELISA was seropositive for 124 of 1030 participants (12%). The more sensitive and specific IFA confirmed SARS in only two cases (0.19%). Both confirmed cases were under 19 years of age and had no known SARS-related risk factors. Conclusion There was low post-epidemic seroprevalence of SARS-CoV in a community adjacent to a hospital which had a nosocomial SARS outbreak. The SARS outbreak in Taiwan was primarily limited to hospital settings.


title: Antibody-dependent enhancement of serotype II feline enteric coronavirus infection in primary feline monocytes

text: Feline coronavirus (FCoV) has been classified into two biotypes: avirulent feline coronavirus (feline enteric coronavirus: FECV) and virulent feline coronavirus (feline infectious peritonitis virus: FIPV). In FIPV infection, antibody-dependent enhancement (ADE) has been reported and was shown to be associated with severe clinical disease. On the other hand, the potential role of ADE in FECV infection has not been examined. In this study, using laboratory strains of serotype II FIPV WSU 79-1146 (FIPV 79-1146) and serotype II FECV WSU 79-1683 (FECV 79-1683), we investigated the relationship between ADE and induction of inflammatory cytokines, which are pathogenesis-related factors, for each strain. As with ADE of FIPV 79-1146 infection, a monoclonal antibody against the spike protein of FCoV (mAb 6-4-2) enhanced FECV 79-1683 replication in U937 cells and primary feline monocytes. However, the ADE activity of FECV 79-1683 was lower than that of FIPV 79-1146. Moreover, mRNA levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) significantly increased with ADE of FIPV 79-1146 infection in primary feline monocytes, but FECV 79-1683 did not demonstrate an increase in these levels. In conclusion, infection of monocytes by FECV was enhanced by antibodies, but the efficiency of infection was lower than that of FIPV.


title: A spatial–temporal analysis of hotels in urban tourism destination

text: Abstract This study investigates the spatial associations of urban tourism phenomena by using GIS and statistical methods to examine the relationships between hotels and land use types, attractions, transportation facilities, and the economic variables of the tertiary planning units in which the hotels are located. Hong Kong is used as an example. The study first introduces the spatial characteristics of hotels and attractions development in Hong Kong. A geographical information system is then used to map hotels and investigate the characteristics of the land use, attractions, and transport facilities around hotels. The spatial relationships are then analyzed with a set of logistic regression models. The results reveal that commercial land type and the number of attractions around hotels are significantly related to the distribution of upper-grade hotels in Hong Kong. The determinants vary over time and the spatial structure changes accordingly. The analysis is important theoretically as it enriches the methodologies for analyzing the relationships between hotels and urban structure, and for conceptualizing and identifying tourism functional zones. It is important for practitioners as it provides useful information for selecting sites for hotels.


title: A catabolic state in a kidney transplant recipient with COVID‐19

text: Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are at risk for acute kidney injury (AKI). Requirements of kidney replacement therapies (KRT) may be particularly intense for kidney transplant recipients with COVID-19 who develop AKI, due to their chronic use of steroids (1) and theoretically higher viral loads (2) that may lead to a catabolic state (3). Herein, we report the case of a kidney transplant recipient with COVID-19 infection, AKI, and a high catabolic state evidenced by refractory hyperkalemia and azotemia.


title: Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013–2014

text: We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar.


title: Outcomes of a Two-Tiered Multifaceted Elderly Suicide Prevention Program in a Hong Kong Chinese Community

text: Objectives 1) To compare the 2-year completed suicide and reattempt rates in a preintervention group of Hong Kong Chinese suicide attempters (aged 65 years and older) who received standard care and a postintervention group enrolled in a regional elderly suicide prevention program (ESPP) that adopts a two-tiered multifaceted care management model and 2) to examine the trend of suicide rates in older adults aged 65 years and older in the pre- and postintervention periods. Design The first part is an observational cohort study with baseline, follow-up, and outcome data being identified from a clinical electronic registry. The second part examines changes in suicide rates from official mortality statistics. Setting A government-funded suicide intervention program serving catchment population (852,796 people aged 65 years and older) in Hong Kong, China. Participants Suicide attempters (aged 65 years and older) presenting to old-age psychiatric service in the pre- and postintervention phases. Measurements 1) Two-year rates of completed suicide and suicide reattempt and 2) changes in population suicide rates in the pre- and postintervention periods. Results The 2-year completed suicide rate was 7.58% in the preintervention group (N = 66) and 1.99$% in the ESPP group (N = 351) χ2 = 6.192; p value: 0.028; df = 1). Reattempt rates were not different. At a population level, suicide rate dropped significantly only in women aged 85 years and older, relative to the preintervention period. Conclusions The ESPP was associated with a reduced rate of completed suicide in old-age suicide attempters and might have contributed to a fall of suicide rate in women aged 85 years and older.


title: Acute Flaccid Myelitis: Characteristics and Outcomes of 2014 and 2016 Cases at a Single Center

text: Acute flaccid myelitis (AFM) is a rare condition associated with spinal cord gray matter abnormalities and frequent persistent motor deficits in the limbs. We present our experience with the diagnosis, management, and outcomes of affected children in 2014 and 2016, emphasizing features that should trigger early consideration of AFM. Early viral testing may increase the rate of detecting associated viruses.


title: The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

text: An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.


title: Complete genome sequences of novel S-deletion variants of porcine epidemic diarrhea virus identified from a recurrent outbreak on Jeju Island, South Korea

text: Porcine epidemic diarrhea virus (PEDV) is a deadly epizootic swine coronavirus that is of importance to the world pork industry. Since the re-emergence of the virulent genotype 2b (G2b) in 2014, Jeju Island in South Korea has faced periodic outbreaks, leading to the occurrence of endemics in provincial herds. In this study, we examined the complete genome sequences and molecular characteristics of novel G2b PEDV variants with a two-amino-acid deletion in the neutralizing epitope of the spike (S) gene, which were concurrently identified on a re-infected farm and its neighboring farm on Jeju Island. Whole-genome sequencing of the Jeju S-DEL isolates KNU-1829 and KNU-1830 revealed the presence of a continuous 9-nucleotide deletion within the nonstructural protein coding region. Their genomes were 28,023 nucleotides in length, 15 nucleotides shorter than those of the classical G2b PEDV strains. The two S-DEL isolates had 96.4–99.2% and 98.3–99.7% identity at the S-gene and full-genome level, respectively, to other global G2b PEDV strains. Genetic and antigenic analyses indicated that the S-DEL isolates are most closely related to the primary strain identified from the initial exposure at the same farm, but the virus appears to undergo continuous evolution, possibly leading to antigenic drift under recurrent or endemic pressure. This study provides important information about the antigenic diversity of PEDV circulating in the endemic areas, which arises from continuous non-lethal mutations to ensure viral fitness in the host environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04360-4) contains supplementary material, which is available to authorized users.


title: Information-seeking preferences of the Colorado equine industry for distribution of disease outbreak information

text: The purpose of this study was to learn how perceptions of accuracy and availability of sources affect how members of the Colorado equine industry seek both everyday information as well as information during an equine disease outbreak. A survey was distributed by email and social media to members of Colorado-based equine organizations. A total of 256 survey responses were obtained from individuals representing a spectrum of ages and roles in the Colorado equine industry. Survey participants predominantly identified as female (95.3%) and their industry role as a horse owner (41%) or a competitive (25.8%) or pleasure (13.3%) rider. Younger survey participants reported greater (P < .0001) use of social media, and both participant age (P < .015) and information source (P < .0001) affected the perception of resource accuracy. In the event of an equine disease outbreak, industry role was an important factor (P = .003) in the selection of news sources, whereas age was not (P = .19). Many participants (56%) identified disease symptoms/signs to be the most important information to be sought during a disease outbreak, and most (69.9%) preferred state or veterinary resources for this information. The identification of why Colorado equine industry members access information from specific sources may guide animal health and Extension professionals to tailor their online presence to best meet the communication needs of the Colorado equine industry.


title: Effective biosecurity to protect North American studs and clients from emerging infectious disease

text: Protecting boar studs and their clients from emerging infectious disease first involves effective biosecurity measures to keep a disease out that was not present, and second, early identification and ceasing semen distribution prior to disseminating infectious disease. Experiences in the field can best guide us as to what has been effective. Circumstances in North America in the period of 1999–2004 resulted in numerous PRRS virus (Porcine Reproductive and Respiratory Syndrome) negative boar studs becoming infected and disseminating virus to sow farms. Earlier detection methods were needed, and withholding of semen pending negative test results became standard. To accomplish this, diagnostic labs complied with industry requests for same day testing. At the same time, research efforts helped clarify the major routes of PRRS virus introduction into the farms. The risk of fomites and aerosol spread became viewed as major risks. Addressing issues with people and supply entry alone did not eliminate new virus entry. The implementation of air filtration during 2005–2008 had a major impact on the rate of new virus introductions into boar studs after other measures alone were unsuccessful. Risks exposed with the introduction of PED virus (Porcine Epidemic Diarrhea) into North America further highlighted other risk factors such as feed ingredients, trailer sanitation, and the presence of clear physical barriers. The successful adaptation of testing procedures, combined with biosecurity procedures including air filtration, has made the incidence of infectious disease introduction extremely rare in North American boar studs over the last decade. While survivability of infectious disease agents can vary in different materials or in the air, successful protocols should be applied and adjusted as needed to accommodate new information or risks. Cleary defined physical barriers for people and animal entry and exit, sanitization and/or down time on incoming supplies, risk mitigation and testing of feed ingredients, and filtration have been keys to changing the incidence of emerging infectious disease introduction into boar studs.


title: Transmission of Influenza on International Flights, May 2009

text: Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone.


title: Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies

text: AIMS: Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported. SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. METHODS AND RESULTS: Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. CONCLUSIONS: This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies.


title: Developing metrics for emergency care research in low- and middle-income countries

text: INTRODUCTION: There is little research on emergency care delivery in low- and middle-income countries (LMICs). To facilitate future research, we aimed to assess the set of key metrics currently used by researchers in these settings and to propose a set of standard metrics to facilitate future research. METHODS: Systematic literature review of 43,109 published reports on general emergency care from 139 LMICs. Studies describing care for subsets of emergency conditions, subsets of populations, and data aggregated across multiple facilities were excluded. All facility- and patient-level statistics reported in these studies were recorded and the most commonly used metrics were identified. RESULTS: We identified 195 studies on emergency care delivery in LMICs. There was little uniformity in either patient- or facility-level metrics reported. Patient demographics were inconsistently reported: only 33% noted average age and 63% the gender breakdown. The upper age boundary used for paediatric data varied widely, from 5 to 20 years of age. Emergency centre capacity was reported using a variety of metrics including annual patient volume (n = 175, 90%); bed count (n = 60, 31%), number of rooms (n = 48, 25%); frequently none of these metrics were reported (n = 16, 8%). Many characteristics essential to describe capabilities and performance of emergency care were not reported, including use and type of triage; level of provider training; admission rate; time to evaluation; and length of EC stay. CONCLUSION: We found considerable heterogeneity in reporting practices for studies of emergency care in LMICs. Standardised metrics could facilitate future analysis and interpretation of such studies, and expand the ability to generalise and compare findings across emergency care settings.


title: Elimination of Porcine Epidemic Diarrhea Virus in an Animal Feed Manufacturing Facility

text: Porcine Epidemic Diarrhea Virus (PEDV) was the first virus of wide scale concern to be linked to possible transmission by livestock feed or ingredients. Measures to exclude pathogens, prevent cross-contamination, and actively reduce the pathogenic load of feed and ingredients are being developed. However, research thus far has focused on the role of chemicals or thermal treatment to reduce the RNA in the actual feedstuffs, and has not addressed potential residual contamination within the manufacturing facility that may lead to continuous contamination of finished feeds. The purpose of this experiment was to evaluate the use of a standardized protocol to sanitize an animal feed manufacturing facility contaminated with PEDV. Environmental swabs were collected throughout the facility during the manufacturing of a swine diet inoculated with PEDV. To monitor facility contamination of the virus, swabs were collected at: 1) baseline prior to inoculation, 2) after production of the inoculated feed, 3) after application of a quaternary ammonium-glutaraldehyde blend cleaner, 4) after application of a sodium hypochlorite sanitizing solution, and 5) after facility heat-up to 60°C for 48 hours. Decontamination step, surface, type, zone and their interactions were all found to impact the quantity of detectable PEDV RNA (P < 0.05). As expected, all samples collected from equipment surfaces contained PEDV RNA after production of the contaminated feed. Additionally, the majority of samples collected from non-direct feed contact surfaces were also positive for PEDV RNA after the production of the contaminated feed, emphasizing the potential role dust plays in cross-contamination of pathogen throughout a manufacturing facility. Application of the cleaner, sanitizer, and heat were effective at reducing PEDV genomic material (P < 0.05), but did not completely eliminate it.


title: Complementary and Integrative Treatments Rhinosinusitis

text: Rhinosinusitis is characterized by inflammation of the mucosa involving the paranasal sinuses and the nasal cavity and is one of the most common health care problems, with significant impairment of quality of life. There is a growing amount of interest in the use of complementary and integrative medicine for the treatment of rhinosinusitis. This article focuses on an integrative approach to rhinosinusitis.


title: Effect of low‐concentration chlorine dioxide gas against bacteria and viruses on a glass surface in wet environments

text: Aims: To evaluate the efficacy of low‐concentration chlorine dioxide (ClO(2)) gas against model microbes in the wet state on a glass surface. Methods and Results: We set up a test room (39 m(3)) and the ClO(2) gas was produced by a ClO(2) gas generator that continuously releases a constant low‐concentration ClO(2) gas. Influenza A virus (Flu‐A), feline calicivirus (FCV), Staphylococcus aureus and Escherichia coli were chosen as the model microbes. The low‐concentration ClO(2) gas (mean 0·05 ppmv, 0·14 mg m(−3)) inactivated Flu‐A and E. coli (>5 log(10) reductions) and FCV and S. aureus (>2 log(10) reductions) in the wet state on glass dishes within 5 h. Conclusions: The treatment of wet environments in the presence of human activity such as kitchens and bathrooms with the low‐concentration ClO(2) gas would be useful for reducing the risk of infection by bacteria and viruses residing on the environmental hard surfaces without adverse effects. Significance and Impact of the Study: This study demonstrates that the low‐concentration ClO(2) gas (mean 0·05 ppmv) inactivates various kinds of microbes such as Gram‐positive and Gram‐negative bacteria, enveloped and nonenveloped viruses in the wet state.


title: Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease

text: The SARS-CoV-2 main protease (Mpro) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant selection pressure, with new Mpro mutations arising over time. Identification and structural characterization of Mpro variants is thus critical for robust inhibitor design. Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Residue substitution is widely distributed, with some tendency toward larger and more hydrophobic residues. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery.