title: Absence of E protein arrests transmissible gastroenteritis coronavirus maturation in the secretory pathway

text: Abstract A recombinant transmissible gastroenteritis coronavirus (rTGEV) in which E gene was deleted (rTGEV-ΔE) has been engineered. This deletion mutant only grows in cells expressing E protein (E+ cells) indicating that E was an essential gene for TGEV replication. Electron microscopy studies of rTGEV-ΔE infected BHK-pAPN-E− cells showed that only immature intracellular virions were assembled. These virions were non-infectious and not secreted to the extracellular medium in BHK-pAPN-E− cells. RNA and protein composition analysis by RNase-gold and immunoelectron microscopy showed that rTGEV-ΔE virions contained RNA and also all the structural TGEV proteins, except the deleted E protein. Nevertheless, full virion maturation was blocked. Studies of the rTGEV-ΔE subcellular localization by confocal and immunoelectron microscopy in infected E− cells showed that in the absence of E protein virus trafficking was arrested in the intermediate compartment. Therefore, the absence of E protein in TGEV resulted in two actions, a blockade of virus trafficking in the membranes of the secretory pathway, and prevention of full virus maturation.


title: Development Path and Urgency of further Strengthening Construction of Public Hospitals Based on Novel Coronavirus Pneumonia Treatment

text: During the outbreak of novel coronavirus pneumonia (NCP) in Wuhan, public hospitals have played an important role in intensive care, case guidance and scheme optimization. At the same time, it also faces unprecedented challenges and tests. Based on the treatment of severe patients in Wuhan, combined with the treatment practice in Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, this paper puts forward the urgency of further strengthening the construction of public hospitals, discusses the feasible path for promoting the development of public hospitals, so as to meet the growing medical needs of the people, improve the ability to respond to major public health emergencies, and effectively guarantee the safety of people’s lives and the promotion of a healthy China construction.


title: The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production

text: Abstract In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both Xenopus oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li+ partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.


Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial


title: Caring for patients with diabetes during COVID-19 pandemic: Important considerations for pharmacists

text: The current pandemic of the COVID-19 infection, coupled with the increased global burden of diabetes, has imposed significant challenges to the healthcare providers in providing effective and sustained care to patients with diabetes care during the ongoing pandemic. It is, therefore, important for healthcare providers to understand and follow the recommended changes in the delivery of care, lifestyle modifications, and pharmacotherapy to ensure optimal care to the patients during and post-pandemic era. This commentary aims to discuss the impact of COVID-19 on diabetes care and the important considerations for pharmacists during this pandemic.


Opinion of the Scientific Panel on biological hazards (BIOHAZ) on the request from the Commission on Meat Inspection Procedures for Lambs and Goats


Proceedings of Réanimation 2018, the French Intensive Care Society International Congress


docid: zebapzje

title: Effects of randomness on viral infection model with application

text: Abstract Virus population disease dynamics in various species of ecosystem keep the research interests alive for many centuries. In this research article, an attempt has been made to understand the qualitative behavior of a virus infection model with Lytic and Non-Lytic Immune Responses by perturbing with randomness (white noise) via Lyapunov technique. The conditions for the extinction and permanence of the viral infection in the interacting populations has been found, analyzed and supported with numerical simulations. An application to HIV infection model has also been presented for drawing a comparative study of the model under various modeling methods. The research findings of this paper reveal that a study that includes random fluctuations of the environment prove to be the ideal way to bring out the qualitative analysis of a mathematical model that will depict the real world scenario.


docid: adsgiizl

title: COVID‐19 indirect contact transmission through the oral mucosa must not be ignored

text: BACKGROUND Coronavirus (CoV) is the single stranded sense RNA virus that has been known so far with the largest genomic capacity and plenty of natural hosts. In the past dozens of years, SARS-CoV under the branch of the new evolutionary tree has threatens greatly global public health and the severe acute respiratory syndrome new coronavirus (COVID-19) reported in China could cause fatal pathological lesions. Especially in areas with poor medical care, neglect of indirect transmission can cause more serious consequences. METHODS First of all, with reference to SARS-CoV and other relevant studies, the possibility of virus residues on the surface of multiple media is discussed. Further, it is found that the surface residue of this substance may be an important factor in iatrogenic infection. RESULTS This correspondence could point out the direction to study the pathomechanism of COVID-19 infecting human beings. CONCLUSIONS Mucosa exposure and inappropriate treatment of medical and non-medical articles used by the patients all could increase the risks of COVID-19 transmission.


title: Prevention is Better than Cure: An Application of Big Data and Geospatial Technology in Mitigating Pandemic

text: COVID-19 has been a severe threat to city’s dense ecosystem and has collapsed the urban life. These spread has raised question on urban health infrastructure and coping capacity. To maintain social distance and providing community with essentials is a challenging task for government and city planners in dense urban area. Spatial mapping of resources, patients, medical infrastructure, potential open space, places which can be turned to quarantine centers, etc. has been done using GIS for city of Surat. Larger open spaces within the urban fabric are identified to implement emergency services and evacuation protocols. This tool will defiantly be helpful to the city administration in maintaining the cluster, quarantine tracking of the infected community and flow of daily essential, supply chain in cities with restriction in the infected cluster. Even having better technology to fight against any pandemic, geospatial technology will help to prevent the pandemic to spread further and hence, it is known as prevention is better then cure.


title: What’s new in the aetiopathogenesis of vasculitis?

text: The cause of the majority of childhood vasculitides is unknown although it is likely that a complex interaction between environmental factors and inherited host responses trigger the disease and determine the vasculitis phenotype. Epidemiological clues continue to implicate infectious triggers in Kawasaki syndrome (KS) and Henoch Schőnlein purpura (HSP). Several genetic polymorphisms have now been described in KS and HSP which predispose to disease or predict disease severity. Anti-neutrophil cytoplasmic antibodies (ANCA) are now known to be directly involved in the pathogenesis of vascular injury in ANCA-associated vasculitides, although why some individuals develop ANCA in the first instance is not yet understood. Endothelial injury and repair are active areas of research in vasculitis. It is now possible to track endothelial injury non-invasively in children with vasculitis using surrogate markers of endothelial injury. The vasculogenic pathways involved in vascular repair following vasculitis, including endothelial progenitor cells, are beginning to be studied. It is anticipated that an improved understanding of the aetiopathogenesis of vasculitis in the young will ultimately shape future novel diagnostic and therapeutic approaches and will help us predict which children may develop premature arteriosclerosis in later life.


title: Coronavirus Papain-like Proteases Negatively Regulate Antiviral Innate Immune Response through Disruption of STING-Mediated Signaling

text: Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.


title: Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

text: Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.


title: Mechanism of demyelination in JHM virus encephalomyelitis: Electron microscopic studies

text: Weanling mice were given intraperitoneal inoculations of the neurotropic, JHM strain of mouse hepatitis virus, the virulence of which had been altered by repeated mouse passages. Five to seven days later many animals developed hind leg paralysis. The pathology consisted of an acute encephalomyelitis with patchy demyelinating lesions in the brain stem and spinal cord. Virus particles, consistent with the appearance of corona viruses, were found in the cytoplasm of cells that were identified as oligondendrocytes by demonstrating connections of their plasma membranes with myelin lamellae. Following the degeneration of oligodendrocytes the myelin sheaths disintegrated or were stripped off intact axons by cytoplasmic tongues of polymorpho- and mononuclear leucocytes that intruded between myelin lamellae. The findings indicate that JHM virus has an affinity for oligodendrocytes in weanling mice and that demyelination occurs subsequently to the degeneration of the infected oligodendrocytes.


title: When Pasteur went to China

text: The recently inaugurated Institut Pasteur of Shanghai-Chinese Academy of Sciences has appointed Vincent Deubel as Director. The institute will focus on major emerging public health problems in Asia.


title: Evaluation of SARS-CoV-2 in Breastmilk from 18 Infected Women

text: To The Editor, Currently, the U.S. Centers for Disease Control and Prevention, American Academy of Pediatrics and the World Health Organization advise that women who are infected with SARS-CoV-2 may choose to breastfeed with appropriate protections to prevent transmission of the virus through respiratory droplets. However, the potential for exposure to SARS-CoV-2 through breastfeeding is currently unknown. To date, case reports on breastmilk samples from a total of 24 SARS-CoV-2-infected women have been published. Of those, viral RNA was detected in ten breastmilk samples from four women. In some but not all cases, environmental contamination as the source of the virus or retrograde flow from an infected infant could not be ruled out. We established a quantitative RT-PCR assay for SARS-CoV-2 in breastmilk with a limit of detection of 250 copies per mL and validated it by spiking breastmilk from uninfected women with known amounts of viral RNA. In addition, we established tissue culture methods to detect replication-competent SARS-CoV-2 in breastmilk. No viral RNA nor culturable virus was detected after Holder pasteurization of breastmilk samples that had been spiked with replication-competent SARS-CoV-2 (see Supplement). Between March 27 and May 6, 2020, we collected and analyzed 64 serial breastmilk samples from 18 SARS-CoV-2-infected women residing in the U.S. (see Supplement for clinical characteristics). Breastmilk samples were collected before and after women had a positive SARS-CoV-2 RT-PCR test and all but one woman had symptomatic disease (see Figure). One of the 64 breastmilk samples had detectable SARS-CoV-2 RNA by RT-PCR. The positive sample was collected on the day of symptom onset but one sample 2 days prior to symptom onset and two subsequent samples, collected 12 and 41 days later, tested negative for viral RNA. In addition, a subset of 26 breastmilk samples from nine women were tested for the presence of replication-competent virus using our established culture methods, and all were negative including the one sample that tested positive for viral RNA by RT-PCR. Although SARS-CoV-2 RNA was detected in one milk sample from one of eighteen infected women, the viral culture for that sample was negative. This suggests that SARS-CoV-2 RNA does not represent replication-competent virus and that breastmilk itself is likely not a source of infection for the infant. Furthermore, when control breastmilk samples spiked with replication-competent SARS-CoV-2 virus were treated by Holder pasteurization, a process commonly performed by donor milk banks, no replication-competent virus nor viral RNA was detectable. Further research to confirm these findings is needed, as well as an examination of convalescent milk for the presence of antibodies against SARS-CoV-2.


title: Frequency of BCoV detection by a semi-nested PCR assay in faeces of calves from Brazilian cattle herds

text: Bovine coronavirus (BCoV) is one of the main causes of neonatal calf diarrhoea. Several diagnostic assays have been employed to detect the presence of the virus in stool samples from calves. Despite this, the frequency of BCoV infection among Brazilian and even South American cattle herds has yet to be well characterised. This study describes the occurrence of BCoV infection among calves from dairy and beef herds in four Brazilian states. A total of 282 stool samples from 1 to 60-day-old calves were evaluated for the presence of BCoV by a semi-nested (SN) PCR assay. The animals were from herds (n = 23) located in three geographical regions in Brazil (south, southeast, and center-west). The specific BCoV amplicon was detected in 15.6% (44/282) of the faecal specimens examined, of which 95.4% (42/44) were from diarrhoeic and 4.6% (2/44) from asymptomatic calves. The specificity of the SN-PCR amplicons was evaluated by restriction fragment length polymorphism (RFLP) analysis. The results show that the BCoV is widespread, mainly among calves from 16 to 30-days-old (p = 0.0023), and verify the association between BCoV infection and clinical signs of diarrhoea (p = 0.005). These findings emphasise the importance of this virus in enteric infections of Brazilian cattle herds.


title: Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial

text: BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a respiratory disease with a case fatality rate of up to 35%. Given its potential to cause a public health emergency and the absence of efficacious drugs or vaccines, MERS is one of the WHO priority diseases warranting urgent research and development of countermeasures. We aimed to assess safety and tolerability of an anti-MERS-CoV modified vaccinia virus Ankara (MVA)-based vaccine candidate that expresses the MERS-CoV spike glycoprotein, MVA-MERS-S, in healthy adults. METHODS: This open-label, phase 1 trial was done at the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Participants were healthy men and women aged 18–55 years with no clinically significant health problems as determined during medical history and physical examination, a body-mass index of 18·5–30·0 kg/m(2) and weight of more than 50 kg at screening, and a negative pregnancy test for women. A key exclusion criterion was a previous MVA vaccination. For the prime immunisation, participants received doses of 1 × 10(7) plaque-forming unit (PFU; low-dose group) or 1 × 10(8) PFU (high-dose group) MVA-MERS-S intramuscularly. A second identical dose was administered intramuscularly as a booster immunisation 28 days after first injection. As a control group for immunogenicity analyses, blood samples were drawn at identical study timepoints from six healthy adults, who did not receive any injections. The primary objectives of the study were safety and tolerability of the two dosage levels and reactogenicity after administration. Immunogenicity was assessed as a secondary endpoint by ELISA and neutralisation tests. T-cell immunity was evaluated by interferon-γ-linked enzyme-linked immune absorbent spot assay. All participants who were vaccinated at least once were included in the safety analysis. Immunogenicity was analysed in the participants who completed 6 months of follow-up. This trial is registered with ClinicalTrials.gov, NCT03615911, and EudraCT, 2014-003195-23 FINDINGS: From Dec 17, 2017, to June 5, 2018, 26 participants (14 in the low-dose group and 12 in the high-dose group) were enrolled and received the first dose of the vaccine according to their group allocation. Of these, 23 participants (12 in the low-dose group and 11 in the high-dose group) received a second dose of MVA-MERS-S according to their group allocation after a 28-day interval and completed follow-up. Homologous prime–boost immunisation with MVA-MERS-S revealed a benign safety profile with only transient mild-to-moderate reactogenicity. Participants had no severe or serious adverse events. 67 vaccine-related adverse events were reported in ten (71%) of 14 participants in the low-dose group, and 111 were reported in ten (83%) of 12 participants in the high-dose group. Solicited local reactions were the most common adverse events: pain was observed in 17 (65%; seven in the low-dose group vs ten in the high-dose group) participants, swelling in ten (38%; two vs eight) participants, and induration in ten (38%; one vs nine) participants. Headaches (observed in seven participants in the low-dose group vs nine in the high-dose group) and fatigue or malaise (ten vs seven participants) were the most common solicited systemic adverse events. All adverse events resolved swiftly (within 1–3 days) and without sequelae. Following booster immunisation, nine (75%) of 12 participants in the low-dose group and 11 (100%) participants in the high-dose group showed seroconversion using a MERS-CoV S1 ELISA at any timepoint during the study. Binding antibody titres correlated with MERS-CoV-specific neutralising antibodies (Spearman's correlation r=0·86 [95% CI 0·6960–0·9427], p=0·0001). MERS-CoV spike-specific T-cell responses were detected in ten (83%) of 12 immunised participants in the low-dose group and ten (91%) of 11 immunised participants in the high-dose group. INTERPRETATION: Vaccination with MVA-MERS-S had a favourable safety profile without serious or severe adverse events. Homologous prime–boost immunisation induced humoral and cell-mediated responses against MERS-CoV. A dose–effect relationship was demonstrated for reactogenicity, but not for vaccine-induced immune responses. The data presented here support further clinical testing of MVA-MERS-S in larger cohorts to advance MERS vaccine development. FUNDING: German Center for Infection Research.


title: Protecting medical staff from skin injury/disease caused by personal protective equipment during epidemic period of COVID‐19: experience from China

text: Linked articles: COVID‐19 SPECIAL FORUM. J Eur Acad Dermatol Venereol 2020; 34: e210–e216.


title: Early outcomes after hip fracture surgery in COVID-19 patients in New York City

text: INTRODUCTION: The COVID-19 pandemic has spread globally and placed healthcare systems under substantial strain. Hip fracture patients represent a high-risk population for severe COVID-19 symptoms, as they are generally older with multiple medical comorbidities. There has been limited information available on the presenting characteristics and outcomes of COVID-positive patients with hip fractures who undergo surgical treatment. METHODS: This was a retrospective study of 10 patients ≥60 years of age with a hip fracture and COVID-19 who underwent surgical treatment in New York City during the COVID-19 outbreak from March 1, 2020 to May 22, 2020. Clinical characteristics and early postoperative outcomes were reported. RESULTS: Eight out of the 10 COVID-positive hip fracture patients in our series were asymptomatic on admission with no clinical signs or symptoms of COVID-19 infection. Only 2 patients presented with hypoxia. All 10 patients underwent surgery within 2 days of admission. Five out of the 10 patients – including the patients who presented with hypoxia – subsequently required supplemental oxygen postoperatively. Two patients had persistently elevated oxygen demands requiring prolonged administration of supplemental oxygen therapy beyond postoperative day 3. None of the patients were put on mechanical ventilation. One patient had a presumed venous thromboembolism postoperatively and subsequently died on postoperative day 19, likely due to respiratory failure. There were no other deaths in the early postoperative period. The average length of inpatient stay was 7.8 days. CONCLUSIONS: Our findings suggest that hip fracture patients who present with asymptomatic or mild COVID-19 infection may have temporarily increased oxygen demands postoperatively, but they can safely undergo early surgical intervention after appropriate medical optimization.


title: Establishment of a simultaneous detection method for ten duck viruses using MALDI-TOF mass spectrometry

text: Abstract Rapid screening of infectious viral diseases is the key to ensure healthy development of duck livestock industry. Currently routine viral detection methods are primarily used to detect up to 3 viruses. In this study, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was used for simultaneous detection and genotyping of ten viruses in duck, including Duck hepatitis A virus 1 (DHAV-1), DHAV-3, Duck astrovirus 1 (DAstV-1), DAstV-2, Duck reovirus 1 (DRV-1), DRV-2, Tembusu virus (TMUV), Avian influenza virus (AIV), Goose parvovirus (GPV) and Duck enteritis virus (DEV). The low detection limits of this proposed method for ten duck viruses ranged from 1.3 copies/μl to 7.8 copies/μl. The novel detection method with high sensitivity, good specificity and high throughput has the potential to be applied for disease diagnosis and surveillance.


title: Virus persistence and recurring demyelination produced by a temperature-sensitive mutant of MHV-4

text: Mouse hepatitis virus type 4 (MHV-4, the JHM strain), a positive-strand RNA virus of the coronavirus family, is well documented as an inducer of acute(1–4) and chronic(5,6) demyelination in mice, as well as subacute demyelination in rats(7,8), due to a cytolytic infection of oligodendrocytes(3,4,7). However, experiments to explore the role of virus and host factors in the production of chronic or recurrent demyelinating disease have been limited because MHV-4 usually produces demyelination in conditions that frequently induce a fatal necrotizing encephalomyelitis(1–9). To circumvent this problem, we had made and selected mutant viruses that caused both a high incidence of demyelination and a low incidence of encephalitis-induced mortality(9). One such mutant, designated ts8, consistently caused acute demyelinating disease in over 90% of intracerebrally or intranasally (natural route of infection) inoculated, 4–5 week-old mice from several susceptible strains within 6–10 days(9,10). In addition, ts8 typically did not cause fatal necrotizing encephalitis, showing a low mortality (<5%)(9,10). This reflected a unique tropism of ts8 for oligodendrocytes, but a limited one for neuronal cells(11). We now report that ts8 is also useful for inducing persistent infection of the mouse central nervous system (CNS). The histopathological correlate of this infection is chronic recurrent demyelination, and virus can be demonstrated ultrastructurally in intact oligodendrocytes, in the vicinity of demyelinated areas.


title: PAK1-blockers: Potential Therapeutics against COVID-19

text: ABSTRACT PAK1 (RAC/CDC42-activated kinase 1) is the major “pathogenic” kinase whose abnormal activation causes a wide variety of diseases/disorders including cancers, inflammation, malaria and pandemic viral infection including influenza, HIV and COVID-19. Since Louis Pateur who developed a vaccine against rabies in 1885, in general a series of “specific” vaccines have been used for treatment of viral infection, mainly because antibiotics in general are ineffective for treatment of viral infection. However, it takes 12–18 months till the effective vaccine becomes available. Until then ventilator (O2 supplier) would be the most common tool for saving the life of COVID-19 patients. Thus, as alternative potentially more direct “broad-spectrum” COVID-19 therapeutics, several natural and synthetic PAK1-blockers such as propolis, melatonin, ciclesonide, hydroxy chloroquine (HQ), ivermection, and ketorolac, which are readily available in the market, are introduced here.


title: Report shows global impact of pandemic on charitable sector

text: A new report from the Charities Aid Foundation shows that the negative impacts of the COVID‐19 pandemic are indeed being felt by nonprofits in communities all around the world.


title: Nonbacterial Myositis

text: Infectious myositis is defined as an infection of a skeletal muscle. Infectious myositis is most commonly caused by bacteria; however, a variety of viral, parasitic, and fungal agents may also cause myositis. The pathogenesis of nonbacterial infectious myositis is via direct or hematogenous infection of the musculature or immune mechanisms. Symptoms typically include muscular pain, tenderness, swelling, and/or weakness. The diagnosis of the specific microbe is often suggested by the presence of concordant clinical signs and symptoms, a detailed medical and travel history, and laboratory data. For example, immunocompromised hosts have a heightened risk of fungal myositis, whereas the presence of a travel history to an endemic location and/or eosinophilia may suggest a parasitic cause. Definitive diagnosis requires detecting the organism by specific laboratory testing including serologies, histopathology, and/or cultures. Treatment entails antimicrobial agents against the pathogen, with consideration for surgical drainage for focal purulent collections within the musculature.


docid: haukpwtf

title: Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro

text: Abstract Mannose-binding lectin (MBL), a pattern-recognition molecule in serum, recognizes specific hexose sugars rich in mannose and N-acetylglucosamine on bacterium, yeasts, viruses as well as apoptotic cells. It has been well-identified that MBL has antiviral effects via binding to seasonal influenza H1 and H3 subtype viruses. Influenza A (H7N9) virus, a novel reassortant virus to human population, possesses the surface hemagglutinin (HA) and neuraminidase (NA) genes from duck and wild-bird influenza viruses and internal genes from poultry H9N2 viruses. As of Dec 7th, 2014, a total of 467 human infections and 183 fatal cases have been identified. Here, recombinant human (rh) MBL was tested for its binding and effects on hemagglutination inhibition (HI) and NA activity inhibition (NAI) of avian H7N9, H9N2 and human H3N2 viruses. We discovered that rhMBL exhibited a strong binding to H7N9 virus as human H3N2 did at high virus titers. However, it performed a significantly weaker HI activity effect on H7N9 comparing to those of H3N2 and H9N2, even at a much higher concentration (3.67 ± 0.33 vs. 0.026 ± 0.001 and 0.083 ± 0.02 μg/mL, respectively). Similarly, minor NAI effect of rhMBL, even at up to 10 μg/mL, was found on H7N9 virus while it displayed significant effects on both H3N2 and H9N2 at a lowest concentration of 0.0807 ± 0.009 and 0.0625 μg/mL, respectively. The HI and NAI effects of rhMBL were calcium-dependent and mediated by lectin domain. Our findings suggest that MBL, the host innate molecule, has differential interference effects with human and avian influenza virus and limited antiviral effect against H7N9 virus.


docid: grmqnooy

title: Dendrimer– and polymeric nanoparticle–aptamer bioconjugates as nonviral delivery systems: a new approach in medicine

text: Aptamers are RNA or DNA oligonucleotides interacting to form unique 3D target conformations with high affinity and specificity, and are emerging as a powerful class of ligands for therapeutic applications. In addition, dendrimers are well-defined nano-sized symmetric polymeric molecules. In this review, we provide an analysis of the use of dendrimers modified with aptamers as nonviral vectors to specifically target tumor cells. Various anticancer agents have been encapsulated with dendrimers complexing with aptamers, including epirubicin, camptothecin, Bcl-xL short hairpin (sh)RNA, and 5-fluorouracil rhodamine-labeled dextran. Other types of polymeric nanoparticle (NP)–aptamer bioconjugates have also been developed and loaded with Pt(IV) derivatives, to target specific tumor cells.


docid: rhbqgjnm

title: Viable Viral Efficiency of N95 and P100 Respirator Filters at Constant and Cyclic Flow

text: The growing threat of an influenza pandemic presents a unique challenge to healthcare workers, emergency responders, and the civilian population. The Occupational Safety and Health Administration (OSHA) recommends National Institute for Occupational Safety and Health (NIOSH)-approved respirators to provide protection against infectious airborne viruses in various workplace settings. The filtration efficiency of selected NIOSH-approved particulate N95 and P100 filtering facepiece respirators (FFRs) and filter cartridges was investigated against the viable MS2 virus, a non-pathogenic bacteriophage, aerosolized from a liquid suspension. Tests were performed under two cyclic flow conditions (minute volumes of 85 and 135 L/min) and two constant flow rates (85 and 270 L/min). The mean penetrations of viable MS2 through the N95 and P100 FFRs/cartridges were typically less than 2 and 0.03%, respectively, under all flow conditions. All N95 and P100 FFR and cartridge models assessed in this study, therefore, met or exceeded their respective efficiency ratings of 95 and 99.97% against the viable MS2 test aerosol, even under the very high flow conditions. These NIOSH-approved FFRs and particulate respirators equipped with these cartridges can be anticipated to achieve expected levels of protection (consistent with their assigned protection factor) against airborne viral agents, provided that they are properly selected, fitted, worn, and maintained.


title: Recombination in large RNA viruses: Coronaviruses

text: Abstract Coronaviruses contain a very large RNA genome, which undergoes recombination at a very high frequency of nearly 25% for the entire genome. Recombination has been demonstrated to occur between viral genomes and between defective-interfering (DI) RNAs and viral RNA. It provides an evolutionary tool for both viral RNAs and DI RNA and may account for the diversity in the genomic structure of coronaviruses. The capacity of coronaviruses to undergo recombination may be related to its mRNA transcription mechanism, which involves discontinuous RNA synthesis, suggesting the nonprocessive nature of the viral polymerase. Recombination is used as a tool for the mutagenesis of viral genomic RNA.


title: Postmortem Lung Findings in an Asthmatic with Coronavirus Disease 2019 (COVID-19)

text: Abstract Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in coronavirus disease 2019 (COVID-19) patients, particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old asthmatic man, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than two weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage (DAD) and a fibrinous pneumonia. The presence of DAD is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS), and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza. The relative contribution of mucus plugging to his hypoxemia is unknown.


title: Role of respiratory viruses in pulmonary exacerbations in children with cystic fibrosis

text: Abstract Background The role of respiratory viruses in cystic fibrosis (CF) exacerbations is incompletely understood. Methods Cross-sectional study of CF children with a pulmonary exacerbation. Mid-turbinate swabs were tested by a direct immunofluorescent antibody assay and a multiplex PCR panel (ResPlex II v2.0, Qiagen). Resplex II was also applied to sputum or throat swab samples. Pulmonary function tests and quality of life and severity scores were recorded. Sputum cell counts, bacterial density and cytokines were measured. Results 26/43 (60.5%) subjects tested positive for at least one respiratory virus by any diagnostic method applied to any sample type. Virus-positive patients were younger (p =0.047), more likely to be male (p =0.029), and had higher CF clinical severity (p =0.041) and lower quality of life (physical) scores (p =0.023) but similar IL-8, neutrophil percentage and elastase levels. Conclusions Compared to non-viral exacerbations, viral-related exacerbations were associated with worse severity and quality of life scores but similar pulmonary inflammation.


title: Pathogen Inactivation: A New Paradigm for Preventing Transfusion-Transmitted Infections

text: Remarkable improvements have been made in blood safety since the onset of the HIV epidemic. However, the current paradigm does not prevent all transfusion-transmitted infections and is reactive to new agents, thus accepting that some patients may be harmed before preventive measures are introduced. Several methods are now available that selectively damage DNA and RNA, thus inactivating pathogens contaminating blood components while not damaging the cells or plasma proteins of the blood component. Clinical trials have been completed and pathogen-inactivated platelets and plasma are widely used in Europe. A recent consensus conference recommended implementation of pathogen inactivation when a feasible and safe method is available that inactivates a broad spectrum of pathogens. The shortcomings of our present paradigm for preventing transfusion-transmitted diseases are described, along with a summary of the status of pathogen inactivation.


docid: nlubwytj

title: Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C)

text: The pathogenesis of postviral olfactory disorder (PVOD) has not been fully elucidated. We investigated morphological changes and innate immune responses in the mouse olfactory mucosa induced by intranasal administration of polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA. Mice received three administrations of saline with or without Poly(I:C), once every 24 h. The olfactory mucosa was harvested at various intervals after the first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9 days, the olfactory neuroepithelium had severely degenerated and behavioral tests demonstrated that the mice showed signs of olfactory deterioration. At 24 days, the structure of the neuroepithelium had regenerated almost completely. Regarding the innate immune responses, many neutrophils had infiltrated the olfactory neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days. Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to a lesser extent, but they still remained in the neuroepithelium at 24 days. Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These findings suggest that the secondary damage caused by the neutrophil-mediated innate immune response plays an important role in the pathogenesis of PVOD.


title: The COVID-19 effect: number of patients presenting to The Mid Yorkshire Hospitals OMFS team with dental infections before and during The COVID-19 outbreak

text: This paper investigates the effect of the COVID-19 outbreak and closure of dental practices on the frequency and severity of dental infections presenting in our emergency department. We compared the mean number of daily emergency department referrals for dental abscesses in the two weeks prior to and following the Chief Dental Officer’s statement advising general dental practitioners to cease routine appointments, the mean number decreased from 1 to 0.37. In contrast, the severity and requirement for admission of these infections rose from 35% to 80%. This highlights the importance of the provision of local urgent dental centres during the COVID-19 outbreak in order to reduce pressure on secondary and tertiary care centres.


Epidemiological models are important tools for guiding COVID-19 interventions


title: SARS Coronavirus E Protein in Phospholipid Bilayers: An X-Ray Study

text: We investigated the structure of the hydrophobic domain of the severe acute respiratory syndrome E protein in model lipid membranes by x-ray reflectivity and x-ray scattering. In particular, we used x-ray reflectivity to study the location of an iodine-labeled residue within the lipid bilayer. The label imposes spatial constraints on the protein topology. Experimental data taken as a function of protein/lipid ratio P/L and different swelling states support the hairpin conformation of severe acute respiratory syndrome E protein reported previously. Changes in the bilayer thickness and acyl-chain ordering are presented as a function of P/L, and discussed in view of different structural models.


title: CFTR modulator therapies – effect on life expectancy in people with cystic fibrosis

text: CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.


title: The Impact of Covid-19 on Community-Based Violence Interventions

text: This paper examines the impact of Covid-19 on community-based violence interventions, especially hospital-based violence interventions and street outreach organizations. Guided by our work in Rochester, New York, we explore how the emergence of covid-19, and the subsequent social restrictions, have hampered the ability of community-based organizations to respond to violence. We also examine ways that community-based organizations can adapt to the challenges associated with Covid-19 and continue providing services to the community.


title: Enhanced surveillance and response approaches for pilgrims and local Saudi populations against emerging Nipah, Zika and Ebola viral diseases outbreaks threats

text: Increasing emergence and spread of Nipah, ZIKV and Ebola case and potential outbreaks threats have been reported in several regions around the globe. Yet, emerging Nipah, Ebola and Zika viral diseases outbreaks have been indirectly linked to substantially globalization of trade and travel, climate change and intense urbanization impact, healthcare and socioeconomic inequities as well in affected community settings. Although no case has been documented in Saudi Arabia, there is a great risk of sudden emergence of any of these viruses and others via introducing among pilgrims coming from endemic regions during ritual ceremonies of mass gatherings. Consequently, promoting and investing on new and sensitive proven effective and innovative surveillance and monitoring approaches, including enhanced risk communication, improved integrated vectors surveillance in addition to improved sustainable highly pathogens surveillance control programs to human motility and environmental sanitation strategies all represent ‘One Health’ approach implementation strategic core. Initiation, development and implementation leaded by Saudi government and international stakeholders’ of new partnership, coordinated response leadership and resource mobilization for multidisciplinary and intersectorial advocacy on emerging viral disease outbreaks, accompanied with R&D roadmap and taskforce is crucial. More efforts in epidemiological and laboratory early screening and surveillance of highly pathogenic germs/microbes, and confirmation of asymptomatic and syndromic cases amongst suspected Hajj and Umrah pilgrims, local vulnerable populations and expatriate workers is vital in generating reliable data and data sharing platform for timely risk communication and tourist information update, appropriate immunization campaigns or safe and efficacious care delivery implementation. Moreover, increase Hajj/Umrah mass gathering emergency outbreak preparedness, pilgrims health education and engagement outreach, pre-, during and post programs coverage and effectiveness is needed through One Health approach integration in attaining pilgrims and local population health safety and security, in advancing Saudi sustainable health development goals.


title: Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a type I membrane-bound protein, is essential for the viral attachment to the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening 312 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we identified that three widely used Chinese medicinal herbs of the family Polygonaceae inhibited the interaction of SARS-CoV S protein and ACE2. The IC50 values for Radix et Rhizoma Rhei (the root tubers of Rheum officinale Baill.), Radix Polygoni multiflori (the root tubers of Polygonum multiflorum Thunb.), and Caulis Polygoni multiflori (the vines of P. multiflorum Thunb.) ranged from 1 to 10μg/ml. Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. These findings suggested that emodin may be considered as a potential lead therapeutic agent in the treatment of SARS.


title: A space–time cluster of adverse events associated with canine rabies vaccine

text: Electronic medical records of a large veterinary practice were used for surveillance of potential space–time clustering of adverse events associated with rabies vaccination in dogs. The study population was 257,564 dogs vaccinated in 169 hospitals in 13 US metropolitan areas during a 24-month period. Using a scan statistic for population rate data, significant space–time clusters were identified involving the Atlanta and Tampa/St. Petersburg areas during a 4-month period. Separate spatial–temporal analyses of these cities using coordinates for individual address coordinates identified one significant patient cluster (P = 0.002), associated with a 23.26 km-radius area in Atlanta (20 adverse events in 702 dogs; 2.85%) from November 2002 through February 2003. This percentage of adverse events was significantly increased after adjustment for host-related factors and the number of concurrent vaccinations.


title: Detection of human coronavirus NL63, human metapneumovirus and respiratory syncytial virus in children with respiratory tract infections in south-west Sweden

text: Two recently detected viruses, human metapneumovirus (hMPV) and coronavirus NL63 (HCoV-NL63), have been associated with acute respiratory tract infections, particularly in young children. This study investigated the frequency of hMPV and HCoV-NL63 infections in Swedish children by screening 221 nasopharyngeal aspirates, collected between November 2003 and May 2005, from 212 children attending the paediatric department of a county hospital in Sweden or submitted from local general practitioners. The samples were originally submitted to be tested for respiratory syncytial virus (RSV), and were examined retrospectively for hMPV and HCoV-NL63 by RT-PCR. Of the 212 patients, 101 were positive for RSV (48%), 22 (10%) were positive for hMPV, and 12 (6%) were positive for HCoV-NL63. The frequency of HCoV-NL63 infection increased from 1% in 2003–2004 to 10% in 2004–2005. Sequence analysis of parts of the coronavirus genomes showed considerable similarity to the HCoV-NL63 prototype sequence. The study demonstrated that HCoV-NL63 and hMPV occur in south-west Sweden with essentially the same frequency, seasonal distribution and clinical characteristics as have been reported in other countries.


title: Blended learning via distance in pre-registration nursing education: A scoping review

text: Abstract Prior to the Covid-19 global pandemic, we reviewed literature and identified comprehensive evidence of the efficacy of blended learning for pre-registration nursing students who learn across distances and/or via satellite campuses. Following a methodological framework, a scoping literature review was undertaken. We searched six databases (EBSCOHOST (CINHAL plus; Education research Complete; Australia/New Zealand Reference Centre); Google Scholar; EMBASE (Ovid) [ERIC (Ovid); Medline (Ovid)]; PubMed: ProQuest Education Journals & ProQuest Nursing & Allied Health Source) for the period 2005–December 2015. Critical appraisal for critiquing qualitative and quantitative studies was undertaken, as was a thematic analysis. Twenty-eight articles were included for review, which reported nursing research (n = 23) and student experiences of blended learning in higher education (n = 5). Four key themes were identified in the literature: active learning, technological barriers, support, and communication. The results suggest that when delivered purposefully, blended learning can positively influence and impact on the achievements of students, especially when utilised to manage and support distance education. Further research is needed about satellite campuses with student nurses, to assist with the development of future educational practice.


title: Hyper-phosphorylation of nsp2-related proteins of porcine reproductive and respiratory syndrome virus

text: Abstract Viruses exploit phosphorylation of both viral and host proteins to support viral replication. In this study, we demonstrate that porcine reproductive and respiratory syndrome virus replicase nsp2, and two nsp2-related −2/−1 frameshifting products, nsp2TF and nsp2N, are hyper-phosphorylated. By mapping phosphorylation sites, we subdivide an extended, previously uncharacterized region, located between the papain-like protease-2 (PLP2) domain and frameshifting site, into three distinct domains. These domains include two large hypervariable regions (HVR) with putative intrinsically disordered structures, separated by a conserved and partly structured interval domain that we defined as the inter-HVR conserved domain (IHCD). Abolishing phosphorylation of the inter-species conserved residue serine918, which is located within the IHCD region, abrogates accumulation of viral genomic and subgenomic RNAs and recombinant virus production. Our study reveals the biological significance of phosphorylation events in nsp2-related proteins, emphasizes pleiotropic functions of nsp2-related proteins in the viral life cycle, and presents potential links to pathogenesis.


title: A rare cause of acute flaccid paralysis: Human coronaviruses

text: Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.


title: Pandémie grippale A/H5N1 et niveau de préparation du Niger: une étude sur les connaissances des soignants et l’organisation générale des soins

text: In industrialized countries, the emergence of potentially pandemic influenza virus has invited reactions consistent with the potential threat represented by these infectious agents. However, with globalization, controlling epidemics depends as much on an effective global coordination of control methods as on preparedness of northern and southern national health care systems, at the core of which are health care workers. Our study was conducted in the National Hospital of Niamey, the main Nigerian hospital. Its objective was to evaluate the knowledge of health care professionals regarding flu pandemic and control of infection. We interviewed 178 nursing staff, doctors and paramedics on the basis of a survey. This study — the first to our knowledge to explore these issues in the African context-revealed that caregivers have a rather good mastery of theoretical knowledge. Nevertheless, beyond theoretical knowledge, miscellaneous factors compromise the effectiveness of the health care structure. Some of them seem to occupy a critical position, particularly the absence of shared references among sanitary authorities and health care professionals, and the weaknesses of global coordination of preventive activities and case management.


title: Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa-DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin

text: High-frequency alleles and/or co-occurring human leukocyte antigen (HLA) alleles across loci appear to be more important than individual alleles, because they might be markers of disease risk that have clinical value as biomarkers for targeted screening or the development of new therapies. To better elucidate the major histocompatibility complex background and to facilitate the experimental use of cynomolgus macaques, Mafa-B, Mafa-DQB1, and Mafa-DRB alleles were characterized and their combinations were investigated from 30 macaques of Vietnamese origin by cloning and sequencing. A total of 48 Mafa-B, 22 Mafa-DQB1, and 42 Mafa-DRB alleles, were detected in this study, respectively. In addition, two Mafa-DQB1 and eight Mafa-DRB alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the macaque from Vietnam might be valuable because >30% of the test animals possessed Mafa-DRB*w304 (30%) and -DQB1*0616 (30%). We report that the combination of major histocompatibility complex (MHC) class I and II alleles, including the combination of DRB3*0403-DRB*w304, DRB1*1013-DRB*w304, and Mafa-B*007:01:01-DRB*w304, which was in 17%, 13%, and 13% of the animals, respectively. Interesting, more than two Mafa-DQB1 alleles detected in one animal in this study suggest that Mafa-DQB1, like Mafa-DRB, might be a duplication in the chromosome, which have ever been documented in cynomolgus monkeys but has not yet been observed in rhesus macaques or other primates. Our results for the high frequency of commonly co-occurring MHC alleles across loci in a cohort of the Vietnamese cynomolgus macaque emphasized the value of this species as a model for biomedical research.


title: Applications of gravity models to evaluate and forecast US international air freight markets post-GFC

text: Abstract In addition to being the world's largest economy, the United States (US) has been the foremost driver of consumer spending, free trade and open skies policies. Trade-driven economic growth and air freight markets have been commonly linked in air transport research. Despite increased security after the 9/11 terrorist attacks, international air imports to the US has continued to grow at a rate faster than consumer spending. This paper aims to evaluate whether gravity models are robust enough to forecast and accurately account for substantial economic shocks such as the Global Financial Crisis (GFC). Our research suggests that US demand for air freight is highly sensitive to transport costs, competition from sea freight and consumer spending patterns of perishable, low value and high value commodities across the 19 commodity groups examined, rather than manufacturing income or factors associated with product origin, which is all the more interesting in the context of the recent protectionist rhetoric of the US administration.


title: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells

text: The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.


The Enteric Virome in Inflammatory Bowel Disease


Respiratory Tract Infections in Athletes


title: Highly convergent synthesis and antiviral activity of (E)-but-2-enyl nucleoside phosphonoamidates

text: Several hitherto unknown (E)-but-2-enyl nucleoside phosphonoamidate analogs (ANPs) were prepared directed with nitrogen reagents by cross-metathesis in water-under ultrasound irradiation. Two diastereoisomers were formally identified by X-ray diffraction. These compounds were evaluated against a large spectrum of DNA and RNA viruses. Among them, the phosphonoamidate thymine analogue 19 emerged as the best prodrug against varicella-zoster virus (VZV) with EC(50) values of 0.33 and 0.39 μM for wild-type and thymidine kinase deficient strains, respectively, and a selectivity index ≥200 μM. This breakthrough approach paves the way for new purine and pyrimidine (E)-but-2-enyl phosphonoamidate analogs.


title: A case-control study evaluating RT-PCR/ESI-MS technology compared to direct fluorescent antibody and xTAG RVP PCR,,

text: Waste nasopharyngeal swabs (N = 244) were evaluated by the reverse-transcriptase polymerase chain reaction/electrospray ionization mass spectrometry PLEX-ID Broad Respiratory Virus Surveillance Kit version 2.5 compared to direct fluorescent antibody and xTAG Respiratory Virus Panel for percent agreement, sensitivity, and specificity. Sensitivity and specificity were 91% (111/122) and 95.1% (116/122), respectively. Sensitivity by virus, except parainfluenza, was 92.9–100%, and specificity was 99–100%.


title: Persistent spatial patterns of interacting contagions

text: The spread of infectious diseases, rumors, fashions, and innovations are complex contagion processes, embedded in network and spatial contexts. While the studies in the former context are intensively expanded, the latter remains largely unexplored. In this paper, we investigate the pattern formation of an interacting contagion, where two infections, A and B, interact with each other and diffuse simultaneously in space. The contagion process for each follows the classical susceptible-infected-susceptible kinetics, and their interaction introduces a potential change in the secondary infection propensity compared to the baseline reproduction number [Formula: see text]. We show that the nontrivial spatial infection patterns arise when the susceptible individuals move faster than the infected and the interaction between the two infections is neither too competitive nor too cooperative. Interestingly, the system exhibits pattern hysteresis phenomena, i.e., quite different parameter regions for patterns exist in the direction of increasing or decreasing [Formula: see text]. Decreasing [Formula: see text] reveals remarkable enhancement in contagion prevalence, meaning that the eradication becomes difficult compared to the single-infection or coinfection without space. Linearization analysis supports our observations, and we have identified the required elements and dynamical mechanism, which suggests that these patterns are essentially Turing patterns. Our work thus reveals new complexities in interacting contagions and paves the way for further investigation because of its relevance to both biological and social contexts.


title: Real-time Communication With Health Care Providers Through an Online Respiratory Pathogen Laboratory Report

text: We implemented a real-time report to distribute respiratory pathogen data for our 8-hospital system to anyone with an Internet connection and a web browser. Real-time access to accurate regional laboratory observation data during an epidemic influenza season can guide diagnostic and therapeutic strategies.


title: Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests

text: BACKGROUND: Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. METHODS: We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. RESULTS: Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. CONCLUSIONS: Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.


title: A novel role for poly(C) binding proteins in programmed ribosomal frameshifting

text: Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.


title: Chapter 4 Communicable Diseases

text: Abstract Sanitation, food control, vaccines, and antibiotics have reduced the toll of communicable diseases, saving millions of lives. Smallpox was eradicated in 1977, and poliomyelitis eradication is close. Measles mortality has reduced drastically yet outbreaks occur where immunization lags. HIV/AIDS emerged in the 1980s, grew into a global pandemic costing millions of lives, and despite progress remains a major global health issue. Malaria and tuberculosis still cause millions of deaths. Influenza pandemics with new, deadly versions continue to appear. Neglected tropical diseases are responding to global donor efforts. Newly emerging diseases move to new regions and became endemic, and deadly localized hemorrhagic fevers threaten to transmit more widely. Rapid mass travel allows infectious diseases in isolated villages to quickly become global threats. New strains of viruses, antibiotic resistance, and microorganisms causing chronic diseases are challenges for infectious disease control requiring continuing political, financial, and scientific support, and much tenacity.


title: Histological pattern in Covid‐19 induced viral rash

text: as stated by Estébanez et al (1), incidence of dermatological affection in covid‐19 patients may be different than reported until now. Datas and evidences are building up every day and we wanted to add a contribution describing the case of a 67‐year‐old patient, caucasian, with moderate obesity, a history of alcoholism and various chronic morbidities. No drug allergy was referred. She was sent to ER due to progressive dyspnoea and fever: after RT‐PCR resulted positive to SARS‐CoV 2, she was admitted to hospital and then intubated a week later due to worsening of the respiratory condition.


title: Modeling the dynamics of viral infections in presence of latently infected cells

text: The study aims to develop a new mathematical model in order to explain the dynamics of viral infections in vivo such as HIV infection. The model includes three classes of cells, takes into account the cure of infected cells in latent period and also incorporates three modes of transmission. The mention modes are modeled by three general incidence functions covering several special cases available in the literature. The basic properties of the model as well as its stability analysis have been carried out rigorously. Further, an application is given and also numerical simulation results have been incorporated supporting the analytical results.


docid: icyosmjn

title: Studies on feline CD8(+) T cell non-cytolytic anti-feline immunodeficiency virus (FIV) activity

text: CD8(+) T cells in FIV-infected cats inhibit feline immunodeficiency virus (FIV) replication by producing a soluble factor(s). In the present study, four SPF cats were experimentally infected with FIV. The period during which the anti-FIV activity of CD8(+) T cells became detectable was investigated, and the presence or absence of this activity in the lymph nodes and spleen was examined. Furthermore, we investigated which step(s) of the FIV replication cycle are affected by this antiviral activity. This antiviral activity became detectable five weeks after FIV infection in early cases, and it was simultaneous with or one week after the induction of humoral immunity. All cats having CD8(+) T cells with anti-FIV activity in the peripheral blood also possessed CD8(+) T cells with anti-FIV activity in the lymph nodes. In contrast, CD8(+) T cells from the spleens of some, but not all cats showed anti-FIV activity. CD8(+) T cell-depleted peripheral blood mononuclear cells were cultured and reconstituted with CD8(+) T cells on day 12 of culture after confirming FIV replication. The number of FIV proviral DNA copies in the cells did not change, but the amount of FIV p24 antigen production in the culture supernatant and the number of FIV mRNA copies in the cells decreased. These findings suggested that CD8(+) T cell anti-FIV activity acts at the level of FIV mRNA synthesis from the FIV proviral DNA, inhibiting FIV replication by a non-cytolytic mechanism.


docid: tvguutak

title: Risk factors for bronchiolitis severity: A retrospective review of patients admitted to the university hospital from central region of Slovenia

text: AIM: Study's objective was to identify risk factors associated with bronchiolitis severity. METHODS: A retrospective chart review of all children <2 years old diagnosed with bronchiolitis at the University Medical Centre Ljubljana between May 2014 and April 2015, who were treated as outpatients (paediatric emergency department, PED group) or as inpatients in the standard hospital setting (WARD group) or in the paediatric intensive care unit (PICU group). Detection of respiratory viruses in nasopharyngeal swab was accomplished by RT‐PCR. Severity was assessed by Wang Respiratory Score and hospitalization longer than 24 hours. RESULTS: The study included 761 children. The three most frequently detected viruses were respiratory syncytial virus (RSV), human rhinovirus (hRV) and human bocavirus (hBoV) (57.5%, 272/473; 25.6%, 121/473; 18.4%, 87/473). Patient groups differed in Wang Respiratory Score for the severity of bronchiolitis (P < 0.001). No differences regarding the causative viruses were found. There was a lower proportion of children with the presence of more than one virus in PICU group compared to other two groups (P = 0.017). The three groups significantly differed in age, birthweight, comorbidities, bronchodilator treatment and antibiotic usage. However, multiple regression analysis revealed that younger age and the use of antibiotics were associated with bronchiolitis severity defined as hospitalization for >24 hours. CONCLUSIONS: Respiratory syncytial virus, hRV and hBoV were the most frequently detected viruses. The majority of patients admitted to the PICU had only one virus detected. Younger age and the use of antibiotics were associated with bronchiolitis severity.


title: Shelter Medicine: Infectious Disease Management in Animal Shelters Lila Miller Kate

text: Unknown


title: Neuraxial labor analgesia in an obese parturient with influenza A H1N1

text: Abstract We describe the use of epidural analgesia in a 39-year-old G2P1 parturient presenting at 38+6 weeks estimated gestation with confirmed influenza A H1N1 and superimposed bilateral pneumonia. Although the patient had an uncomplicated intra- and post-partum course, little is known about the safety of performing neuraxial analgesia or anesthesia in patients with influenza. The prevalence of viremia and possible translocation of blood-borne virus to the central nervous system are discussed.


title: Environmental contamination by SARS-CoV-2 of an imported case during incubation period

text: Abstract We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.


title: Implications of SARS-CoV-2 Genetic Diversity and Mutations on Pathogenicity of COVID-19 and Biomedical Interventions

text: ABSTRACT Objective Coronavirus disease 2019 (COVID-19) has caused an unprecedented global health emergency. The COVID-19 pandemic has claimed over 350,000 human lives within five months of its emergence, especially in the USA and the European continent. This study analysed the implications of the genetic diversity and mutations in SARS-CoV-2 on its virulence diversity and investigated how these factors could affect the successful development and application of antiviral chemotherapy, immunotherapy, serodiagnosis, and vaccination. Methods All the suitable and eligible full text articles published between 31st December 2019 and 31st May 2020 were filtered and extracted from “PubMed”, “Scopus”, “Web of Science”, and “Hinari” and were critically reviewed. We used the Medical Subject Headings (MeSH) terms “COVID-19, “Mutation”, “Genetic diversity”, “SARS-CoV-2”, “Virulence”, “Pathogenicity”, “Evolution” and “SARS-CoV-2 transmission” for this search. Results Our search showed that SARS-CoV-2 has persistently undergone significant mutations in various parts of its non-structural proteins (NSPs), including NSP2 and NSP3, S protein, and RNA-dependent RNA polymerase (RdRp). In particular, the S protein was found to be the key determinant of evolution, transmission, and virulence of SARS-CoV-2, and could be a potential target for vaccine development. Additionally, RdRp could be a major target in the development of antivirals for the treatment of COVID-19. Conclusion Given the critical importance of mutations in the pathogenicity of SARS-CoV-2 and in the development of sero-diagnostics, antivirals, and vaccines, this study recommends continuous molecular surveillance of SARS-CoV-2. This approach would potentially prompt identification of new mutants and their impact on ongoing biomedical interventions and COVID-19 control measures.


title: Use of renin–angiotensin–aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study

text: BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin–angiotensin–aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62–2·41) and risk factors (1·46, 1·23–1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77–1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64–1·00) or angiotensin-receptor blockers (1·10, 0·88–1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34–0·80). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.


title: Anti-HCV, nucleotide inhibitors, repurposing against COVID-19

text: Abstract Aims A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp). Materials and methods In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin. Key findings The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease. Significance The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.


title: Enteric Virus Diversity Examined by Molecular Methods in Brazilian Poultry Flocks

text: Enteric viruses play an important role in the Brazilian poultry industry due to the economic impact of resulting low yields of broilers, layers, and breeders. The most common enteric viruses affecting commercial flocks in Brazil include Fowl Adenovirus of group I (FAdV-I), Chicken Parvovirus (ChPV), Chicken Astrovirus (CAstV), Avian Nephritis Virus (ANV), Infectious Bronchitis Virus (IBV), Avian Reovirus (AReo), and Avian Rotavirus (ARtV). The aim of this study was to identify single and multiple infections using data obtained from 270 samples from eleven Brazilian states, corresponding to the period between 2010 and 2017. This was accompanied by an analysis of the relationship between the age of birds, clinical signs, and geographical distribution, using Polymerase Chain Reaction (PCR) and Reverse Transcription-PCR (RT-PCR) techniques. Twenty-five profiles of virus combinations were detected. Single infections were encountered in 86.3% of samples, and multiple infections were present in the remaining 13.7%. Both single and multiple infections affected all kinds of commercial chickens with digestive problems, stunting syndrome, decreases in egg and meat production, increased mortality, and respiratory signs. FAdV-I, ChPV, CAstV, ANV, and ARtV were mostly detected in young broilers, in contrast with IBV, which was detected in hens from one to greater than 51 weeks of age. These results exhibit the complexity of enteric diseases and the still poorly understood role of each pathogen as a unique etiological agent.


title: Factors Associated with Preventive Behaviours of COVID-19 among Hospital Staff in Iran in 2020: An Application of the Protection Motivation Theory

text: Abstract This study was conducted for predicting preventive behaviours of healthcare workers (HCW) towards Covid-19 based on the Protection Motivation Theory (PMT). This cross-sectional and analytical study was conducted on 761 HCW in Hamadan, Iran, using multi-stage random sampling. The preventive behaviours against COVID-19 among HCW were assessed at a relatively desirable level. Based on the PMT, threat and coping appraisal were predictors of protection motivation to conduct COVID-19 preventive behaviours (P<0.001). The intention was also predictive of COVID-19 preventive behaviours (P<0.001). Consideration of personnel's self-efficacy and their knowledge regarding the effectiveness of protective behaviours in designing staff training programs are recommended.


title: Respiratory hygiene in emergency departments: Compliance, beliefs, and perceptions

text: BACKGROUND: Low respiratory hygiene compliance among health care workers of emergency departments has become a major concern in the spread of respiratory infections. Our objective was to determine the compliance with respiratory hygiene of triage nurses at 2 university hospital centers and to identify factors influencing compliance to the respiratory hygiene principles of emergency health care workers. METHODS: A 2-part, cross-sectional, descriptive study was conducted at 2 training centers. An anonymous observation of compliance with respiratory hygiene by triage emergency nurses was performed. A self-administered, voluntary questionnaire on attitudes, perceptions, and knowledge of respiratory hygiene guidelines was distributed to the health care workers at the emergency department of the 2 hospital sites. RESULTS: Median objective compliance with respiratory hygiene measures of triage nurses was 22% (interquartile range [IQR], 11%-33%). Median perceived compliance of the health care workers was 68% (IQR, 61%-79%). Median actual knowledge score was 75% (IQR, 75%-100%). Overall, 91.9% of respondents believed that the mask was an effective preventive measure. The main obstacles toward mask wearing by the health care worker were “tendency to forget” (37.8%) and “discomfort” (35.1%). CONCLUSION: The compliance rate at our institution is very low. We identified a few factors affecting adherence to respiratory hygiene measures that are of potential use in targeting groups and formulating recommendations.


title: Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine

text: Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B(0)AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B(0)AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible short- and long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B(0)AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. Gastric emptying was delayed by intragastric application of an amino acid cocktail but we observed no acute dietary regulation of B(0)AT1 protein expression and L-isoleucine transport. Investigation of the chronic dietary regulation of B(0)AT1, ACE2 and CD13 by different diets revealed an increased B(0)AT1 protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B(0)AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine.


title: Health care workers’ perceptions and reported use of respiratory protective equipment: A qualitative analysis

text: BACKGROUND: Little is known about health care workers’ (HCW) perceptions of, or experiences using, respiratory protective equipment (RPE). We sought to characterize their perceptions and identify reasons underlying inappropriate use. METHODS: We conducted 12 focus groups with nurses and nursing assistants at 4 medical centers. We analyzed the thematic content of 73 discrete “stories” told by focus group participants. RESULTS: We identified 5 story types surrounding RPE use: 1) policies are known and seen during work routines; 2) during protocol lapses, use is reinforced through social norms; 3) clinical experiences sometimes supersede protocol adherence; 4) when risk perception is high, we found concern regarding accessing RPE; and 5) HCWs in emergency departments were viewed as not following protocol because risk was ever-present. DISCUSSION: HCWs were aware of the importance of RPE and protocols for using it, and these supported use when protocol lapses occurred. However, protocol adherence was undermined by clinical experience, perceived risk, and the distinct context of the emergency department where patients continually arrive with incomplete or delayed diagnoses. CONCLUSIONS: Protocols, visual cues, and social norms contribute to a culture of safety. This culture can be undermined when HCWs experience diagnostic uncertainty or they mistrust the protocol and instead rely on their clinical experiences.


title: Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses

text: BACKGROUND: Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain. RESULTS: The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection. CONCLUSION: These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.


title: Therapeutic strategies for critically ill patients with COVID-19

text: Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.


title: Mutational Analysis of the SARS Virus Nsp15 Endoribonuclease: Identification of Residues Affecting Hexamer Formation

text: The severe acute respiratory syndrome (SARS) coronavirus virus non-structural protein 15 is a Mn2+-dependent endoribonuclease with specificity for cleavage at uridylate residues. To better understand structural and functional characteristics of Nsp15, 22 mutant versions of Nsp15 were produced in Escherichia coli as His-tagged proteins and purified by metal-affinity and ion-exchange chromatography. Nineteen of the mutants were soluble and were analyzed for enzymatic activity. Six mutants, including four at the putative active site, were significantly reduced in endoribonuclease activity. Two of the inactive mutants had unusual secondary structures compared to the wild-type protein, as measured by circular dichroism spectroscopy. Gel-filtration analysis, velocity sedimentation ultracentrifugation, and native gradient pore electrophoresis all showed that the wild-type protein exists in an equilibrium between hexamers and monomers in solution, with hexamers dominating at micromolar protein concentration, while native gradient pore electrophoresis also revealed the presence of trimers. A mutant in the N terminus of Nsp15 was impaired in hexamer formation and had low endoribonuclease activity, suggesting that oligomerization is required for endoribonuclease activity. This idea was supported by titration experiments showing that enzyme activity was strongly concentration-dependent, indicating that oligomeric Nsp15 is the active form. Three-dimensional reconstruction of negatively stained single particles of Nsp15 viewed by transmission electron microscopic analysis suggested that the six subunits were arranged as a dimer of trimers with a number of cavities or channels that may constitute RNA binding sites.


title: Management of the ACC/AHA Stage D Patient Cardiac Transplantation

text: Over the last 4 decades, cardiac transplantation has become the preferred therapy for select patients with end-stage heart disease. Heart transplantation is indicated in patients with heart failure despite optimal medical and device therapy, manifesting as intractable angina, refractory heart failure, or intractable ventricular arrhythmias. This article provides an overview of heart transplantation in the current era, focusing on the evaluation process for heart transplantation, the physiology of the transplanted heart, immunosuppressive regimens, and early and long-term complications.


title: China's unique role in the field of global health

text: Abstract China's participation in global governance, inspired by the 17 United Nations Sustainable Development Goals, is driven by the guiding principle of “building a community of shared future for mankind”. China has been promoting the Belt and Road Initiative and South-South Cooperation and has made significant contributions to the prosperity of human beings. Along with the opportunities that globalization brought about such as the World Health Organization and the boom in the economy, global health challenges also emerged. This resulted in certain obstacles for China when it sought to advocate the Belt and Road Initiative and when it attempted to carry out its strategy to address global health issues. What are the emerging challenges for global health? What can China do for global health? Why does global health need China? We tried to address these questions as China's global engagement continues to expand in the new era. This article makes the case for Chinese approaches, including getting involved in public health, being consistent in addressing local conditions, sharing China's experience with handling health services, and strengthening government-led action while being guided by relative policies. China has a lot to offer in the promotion of global health and in overcoming the challenges and risks that this goal currently faces. Thus, China should be considered an inseparable part of global health governance and bilateral health development cooperation.


title: Future of Medical Decision Support Systems

text: After having an introduction to the essential topics, the previous chapters have all provided effective use of deep learning for diagnosis of important diseases, as they are base for the medical decision support systems. There are of course many more research aspects to be discussed but if is also a good approach to focus on some insights regarding future of medical decision support systems.


title: Environmental Cleaning in Resource-Limited Settings

text: PURPOSE OF REVIEW: Environmental surfaces in healthcare facilities, particularly in a patient room, are a critical pathway for healthcare-associated pathogen transmission. Despite well-established guides and recommendations regarding environmental surface cleaning and disinfection, there are several challenges in resource-limited settings. This viewpoint article will discuss the practice of environmental cleaning in resource-limited settings including challenges and relationship between environment and healthcare-associated infections in this setting and outlines pre-requisites to overcome these challenges. RECENT FINDINGS: Despite several barriers and challenges, environmental cleaning is a crucial component to help reduce transmission of healthcare-associated infections and multi-drug-resistant pathogens as well as emerging infectious disease-associated pathogens in resource-limited settings. However, there is a need to develop a multi-modal strategy together with a mechanism for monitor and feedback to improve the practices of environmental cleaning in resource-limited settings. SUMMARY: Additional researches on the barriers and implementation gaps and the role of collaborative network as well as how to apply technology would provide significant insights on the practices of environmental cleaning in resource-limited settings.


title: Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention

text: In 2019/2020, the emergence of coronavirus disease 2019 (COVID‐19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID‐19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts. Multi‐drug regimens are traditionally designed by selecting drugs based on their mechanism of action. This is followed by dose‐finding to achieve drug synergy. This approach is widely‐used for drug development and repurposing. Realizing synergistic combinations, however, is a substantially different outcome compared to globally optimizing combination therapy, which realizes the best possible treatment outcome by a set of candidate therapies and doses toward a disease indication. To address this challenge, the results of Project IDentif.AI (Identifying Infectious Disease Combination Therapy with Artificial Intelligence) are reported. An AI‐based platform is used to interrogate a massive 12 drug/dose parameter space, rapidly identifying actionable combination therapies that optimally inhibit A549 lung cell infection by vesicular stomatitis virus within three days of project start. Importantly, a sevenfold difference in efficacy is observed between the top‐ranked combination being optimally and sub‐optimally dosed, demonstrating the critical importance of ideal drug and dose identification. This platform is disease indication and disease mechanism‐agnostic, and potentially applicable to the systematic N‐of‐1 and population‐wide design of highly efficacious and tolerable clinical regimens. This work also discusses key factors ranging from healthcare economics to global health policy that may serve to drive the broader deployment of this platform to address COVID‐19 and future pandemics.