Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir

Measurement of the production of charm jets tagged with D0^{0} mesons in pp collisions at s\sqrt{s}= 7 TeV

The production of charm jets in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=7$ TeV was measured with the ALICE detector at the CERN Large Hadron Collider. The measurement is based on a data sample corresponding to a total integrated luminosity of $6.23$ ${\rm nb}^{-1}$, collected using a minimum-bias trigger. Charm jets are identified by the presence of a D$^0$ meson among their constituents. The D$^0$ mesons are reconstructed from their hadronic decay D$^0\rightarrow$K$^{-}\pi^{+}$. The D$^0$-meson tagged jets are reconstructed using tracks of charged particles (track-based jets) with the anti-$k_{\mathrm{T}}$ algorithm in the jet transverse momentum range $5<p_{\rm{T,jet}}^{\mathrm{ch}}<30$ ${\rm GeV/}c$ and pseudorapidity $|\eta_{\rm jet}|<0.5$. The fraction of charged jets containing a D$^0$-meson increases with $p_{\rm{T,jet}}^{\rm{ch}}$ from $0.042 \pm 0.004\, \mathrm{(stat)} \pm 0.006\, \mathrm{(syst)}$ to $0.080 \pm 0.009\, \rm{(stat)} \pm 0.008\, \rm{(syst)}$. The distribution of D$^0$-meson tagged jets as a function of the jet momentum fraction carried by the D$^0$ meson in the direction of the jet axis ($z_{||}^{\mathrm{ch}}$) is reported for two ranges of jet transverse momenta, $5<p_{\rm{T,jet}}^{\rm{ch}}<15$ ${\rm GeV/}c$ and $15<p_{\rm{T,jet}}^{\rm{ch}}<30$ ${\rm GeV/}c$ in the intervals $0.2<z_{||}^{\rm{ch}}<1.0$ and $0.4<z_{||}^{\rm{ch}}<1.0$, respectively. The data are compared with results from Monte Carlo event generators (PYTHIA 6, PYTHIA 8 and Herwig 7) and with a Next-to-Leading-Order perturbative Quantum Chromodynamics calculation, obtained with the POWHEG method and interfaced with PYTHIA 6 for the generation of the parton shower, fragmentation, hadronisation and underlying event.Comment: 29 pages, 8 captioned figures, 3 tables, authors from page 24, published version, figures at http://alice-publications.web.cern.ch/node/525

Energy dependence of exclusive J/ψJ/\psi photoproduction off protons in ultra-peripheral p-Pb collisions at sNN\sqrt{s_{\rm{NN}}} = 5.02 TeV

The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of $J/\psi$ vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair $\sqrt{s_{\rm NN}} = 5.02$ TeV. The e$^+$e$^-$ and $\mu^+\mu^-$ decay channels are used to measure the cross section as a function of the rapidity of the $J/\psi$ in the range $-2.5 < y < 2.7$, corresponding to an energy in the $\gamma$p centre-of-mass in the interval $40 < W_{\gamma\mathrm{p}}<550$ GeV. The measurements, which are consistent with a power law dependence of the exclusive $J/\psi$ photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.Comment: 25 pages, 3 captioned figures, 3 tables, authors from page 19, published version, figures at http://alice-publications.web.cern.ch/node/455

Infection with Mers-Cov Causes Lethal Pneumonia in the Common Marmoset

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies

A systematic review of contamination (aerosol, splatter and droplet generation) associated with oral surgery and its relevance to COVID-19

IntroductionThe current COVID-19 pandemic caused by the SARS-CoV-2 virus has impacted the delivery of dental care globally and has led to re-evaluation of infection control standards. However, lack of clarity around what is known and unknown regarding droplet and aerosol generation in dentistry (including oral surgery and extractions), and their relative risk to patients and the dental team, necessitates a review of evidence relating to specific dental procedures. This review is part of a wider body of research exploring the evidence on bioaerosols in dentistry and involves detailed consideration of the risk of contamination in relation to oral surgery.MethodsA comprehensive search of Medline (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science, LILACS and ClinicalTrials.Gov was conducted using key terms and MeSH (Medical Subject Headings) words relating to the review questions. Methodological quality including sensitivity was assessed using a schema developed to measure quality aspects of studies using a traffic light system to allow inter- and intra-study overview and comparison. A narrative synthesis was conducted for assessment of the included studies and for the synthesis of results.ResultsEleven studies on oral surgery (including extractions) were included in the review. They explored microbiological (bacterial and fungal) and blood (visible and/or imperceptible) contamination at the person level (patients, operators and assistants) and/or at a wider environmental level, using settle plates, chemiluminescence reagents or air samplers; all within 1 m of the surgical site. Studies were of generally low to medium quality and highlighted an overall risk of contaminated aerosol, droplet and splatter generation during oral surgery procedures, most notably during removal of impacted teeth using rotatory handpieces. Risk of contamination and spread was increased by factors, including proximity to the operatory site, longer duration of treatment, higher procedural complexity, non-use of an extraoral evacuator and areas involving more frequent contact during treatment.ConclusionA risk of contamination (microbiological, visible and imperceptible blood) to patients, dental team members and the clinical environment is present during oral surgery procedures, including routine extractions. However, the extent of contamination has not been explored fully in relation to time and distance. Variability across studies with regards to the analysis methods used and outcome measures makes it difficult to draw robust conclusions. Further studies with improved methodologies, including higher test sensitivity and consideration of viruses, are required to validate these findings

High workload and job stress are associated with lower practice performance in general practice: an observational study in 239 general practices in the Netherlands

Contains fulltext : 80493.pdf (publisher's version ) (Open Access)BACKGROUND: The impact of high physician workload and job stress on quality and outcomes of healthcare delivery is not clear. Our study explored whether high workload and job stress were associated with lower performance in general practices in the Netherlands. METHODS: Secondary analysis of data from 239 general practices, collected in practice visits between 2003 to 2006 in the Netherlands using a comprehensive set of measures of practice management. Data were collected by a practice visitor, a trained non-physician observer using patients questionnaires, doctors and staff. For this study we selected five measures of practice performance as outcomes and six measures of GP workload and job stress as predictors. A total of 79 indicators were used out of the 303 available indicators. Random coefficient regression models were applied to examine associations. RESULTS AND DISCUSSION: Workload and job stress are associated with practice performance.Workload: Working more hours as a GP was associated with more positive patient experiences of accessibility and availability (b = 0.16). After list size adjustment, practices with more GP-time per patient scored higher on GP care (b = 0.45). When GPs provided more than 20 hours per week per 1000 patients, patients scored over 80% on the Europep questionnaire for quality of GP care.Job stress: High GP job stress was associated with lower accessibility and availability (b = 0.21) and insufficient practice management (b = 0.25). Higher GP commitment and more satisfaction with the job was associated with more prevention and disease management (b = 0.35). CONCLUSION: Providing more time in the practice, and more time per patient and experiencing less job stress are all associated with perceptions by patients of better care and better practice performance. Workload and job stress should be assessed by using list size adjusted data in order to realise better quality of care. Organisational development using this kind of data feedback could benefit both patients and GP

Surgically generated aerosol and mitigation strategies: combined use of irrigation, respirators and suction massively reduces particulate matter aerosol

Background Aerosol is a health risk to theatre staff. This laboratory study quantifies the reduction in particulate matter aerosol concentrations produced by electrocautery and drilling when using mitigation strategies such as irrigation, respirator filtration and suction in a lab environment to prepare for future work under live OR conditions. Methods We combined one aerosol-generating procedure (monopolar cutting or coagulating diathermy or high-speed diamond- or steel-tipped drilling of cadaveric porcine tissue) with one or multiple mitigation strategies (instrument irrigation, plume suction and filtration using an FFP3 respirator filter) and using an optical particle counter to measure particulate matter aerosol size and concentrations. Results Significant aerosol concentrations were observed during all aerosol-generating procedures with concentrations exceeding 3 × 106 particles per 100 ml. Considerable reductions in concentrations were observed with mitigation. In drilling, suction, FFP3 filtration and wash alone respectively reduced aerosol by 19.3–31.6%, 65.1–70.8% and 97.2 to > 99.9%. The greatest reduction (97.38 to > 99.9%) was observed when combining irrigation and filtration. Coagulating diathermy reduced concentrations by 88.0–96.6% relative to cutting, but produced larger particles. Suction alone, and suction with filtration reduced aerosol concentration by 41.0–49.6% and 88.9–97.4% respectively. No tested mitigation strategies returned aerosol concentrations to baseline. Conclusion Aerosol concentrations are significantly reduced through the combined use of filtration, suction and irrigation. Further research is required to characterise aerosol concentrations in the live OR and to find acceptable exposure limits, and in their absence, to find methods to further reduce exposure to theatre staff