title: Les effets épigénétiques du cannabis / tétrahydrocannabinol

text: Résumé La diffusion, sur un mode quasi pandémique, du cannabis chez les adolescents et adultes jeunes, spécialement en France, justifie l’attention portée aux conséquences, non seulement aiguës, mais également différées de cette intoxication. Dans cette dernière éventualité interviennent des mécanismes épigénétiques. On rappellera d’abord différents types de modifications épigénétiques portant soit sur les histones de la chromatine, principalement des méthylations ou des acétylations ; soit sur l’ADN, par méthylation des cytosines. Des modifications de ce type suscitées par le tétrahydrocannabinol/THC du cannabis peuvent intervenir : soit au niveau des gamètes avant la procréation ; soit sur le fœtus pendant la gestation ; soit à différents moments de la vie de l’individu. À certaine de ces modifications épigénétiques est associé un accroissement de la vulnérabilité aux toxicomanies, impliquant les récepteurs D2 de la dopamine dans le noyau accumbens ; une surexpression de la synthèse du précurseur des enképhalines ; des modifications : des récepteurs CB1 des endocannabinoïdes ; des récepteurs de l’acide glutamique ; du GABA ; de protéines impliquées dans la plasticité synaptique, etc. Des modifications épigénétiques peuvent aussi affecter : le système immunitaire ; les activités cognitives ; le développement d’affections psychiatriques en relation avec des perturbations de la maturation cérébrale. Les connaissances qui s’accumulent à cet égard vont à l’opposé de la banalisation ambiante du cannabis. Elles imposent d’alerter les pouvoirs publics et le public, spécialement les jeunes, sur les risques associées à la consommation de cette drogue. Summary The almost pandemic spread of cannabis among adolescents and young adults, especially in France, justifies the attention given to the consequences, not only acute but also delayed, of this intoxication. In the latter case, epigenetic mechanisms occur. We will first recall various types of epigenetic modifications involving either chromatin histones, mainly methylations or acetylations; either DNA, by methylation of cytosines. Such modifications caused by the tetrahydrocannabinol/THC of cannabis can intervene: either at the level of gametes before procreation, or at different points of the life cycle. These epigenetic modifications are associated with an increase in vulnerability to drug addiction, involving dopamine D2 receptors in the nucleus accumbens, overexpression of enkephalin precursor synthesis, modifications of: CB1 receptors of endocannabinoids, glutamic acid receptors, GABA receptors, proteins involved in synaptic plasticity ... These changes can also affect: immune system, cognitive activities, development of psychiatric diseases, related to disturbances of brain maturation. The knowledge that accumulates in this respect is the opposite of the ambient trivialization of this drug. They impose sending an alert to the public authorities and to the public, especially young people, warning on the risks associated with this drug use and abuse.


title: A Case Study Evaluating the Risk of Infection from Middle Eastern Respiratory Syndrome Coronavirus (MERS‐CoV) in a Hospital Setting Through Bioaerosols

text: Middle Eastern respiratory syndrome, an emerging viral infection with a global case fatality rate of 35.5%, caused major outbreaks first in 2012 and 2015, though new cases are continuously reported around the world. Transmission is believed to mainly occur in healthcare settings through aerosolized particles. This study uses Quantitative Microbial Risk Assessment to develop a generalizable model that can assist with interpreting reported outbreak data or predict risk of infection with or without the recommended strategies. The exposure scenario includes a single index patient emitting virus‐containing aerosols into the air by coughing, leading to short‐ and long‐range airborne exposures for other patients in the same room, nurses, healthcare workers, and family visitors. Aerosol transport modeling was coupled with Monte Carlo simulation to evaluate the risk of MERS illness for the exposed population. Results from a typical scenario show the daily mean risk of infection to be the highest for the nurses and healthcare workers (8.49 × 10(−4) and 7.91 × 10(−4), respectively), and the lowest for family visitors and patients staying in the same room (3.12 × 10(−4) and 1.29 × 10(−4), respectively). Sensitivity analysis indicates that more than 90% of the uncertainty in the risk characterization is due to the viral concentration in saliva. Assessment of risk interventions showed that respiratory masks were found to have a greater effect in reducing the risks for all the groups evaluated (>90% risk reduction), while increasing the air exchange was effective for the other patients in the same room only (up to 58% risk reduction).


title: Assessing restoration benefit of grassland ecosystem incorporating preference heterogeneity empirical data from Inner Mongolia Autonomous Region

text: The evaluation of grassland ecosystem restoration benefit considering herdsmen's preference is an important reference for the formulation of grassland protection policy. This study aims to evaluate the marginal benefits of grassland ecosystem services by using choice experiment and mixed logit (ML) model, and a latent class model (LCM) is estimated to identify and explain the heterogeneity of herdsmen's preference for the various functions of the grassland ecosystem, so as to estimate the benefits of grassland ecosystem restoration in Siziwang Banner and Damao Banner of Inner Mongolia Autonomous Region. The results reveal that the restoration benefit of the grassland ecosystem in the two banners is nearly 341.1 million RMB per year. The application of latent class model highlights three potential segments of the herdsmen with different preferences. The social, economic and environmental attitudinal characteristics of herdsmen have significant impacts on their preferences. Thus, to improve the universality of grassland ecological restoration policy, herdsmen's preferences should be thoroughly investigated before policy formulation and implementation. Meanwhile, it is important to publicize the grassland ecosystem services, to popularize the role of wildlife in the ecosystem, and to realize the benign interaction between wildlife protection and animal husbandry development.


title: The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other Viruses

text: Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine.


title: Evolution and variation of 2019-novel coronavirus

text: Background The current outbreak caused by novel coronavirus (2019-nCoV) in China has become a worldwide concern. As of 28 January 2020, there were 4631 confirmed cases and 106 deaths, and 11 countries or regions were affected. Methods We downloaded the genomes of 2019-nCoVs and similar isolates from the Global Initiative on Sharing Avian Influenza Database (GISAID and nucleotide database of the National Center for Biotechnology Information (NCBI). Lasergene 7.0 and MEGA 6.0 softwares were used to calculate genetic distances of the sequences, to construct phylogenetic trees, and to align amino acid sequences. Bayesian coalescent phylogenetic analysis, implemented in the BEAST software package, was used to calculate the molecular clock related characteristics such as the nucleotide substitution rate and the most recent common ancestor (tMRCA) of 2019-nCoVs. Results An isolate numbered EPI_ISL_403928 showed different phylogenetic trees and genetic distances of the whole length genome, the coding sequences (CDS) of ployprotein (P), spike protein (S), and nucleoprotein (N) from other 2019-nCoVs. There are 22, 4, 2 variations in P, S, and N at the level of amino acid residues. The nucleotide substitution rates from high to low are 1·05 × 10−2 (nucleotide substitutions/site/year, with 95% HPD interval being 6.27 × 10−4 to 2.72 × 10−2) for N, 5.34 × 10−3 (5.10 × 10−4, 1.28 × 10−2) for S, 1.69 × 10−3 (3.94 × 10−4, 3.60 × 10−3) for P, 1.65 × 10−3 (4.47 × 10−4, 3.24 × 10−3) for the whole genome, respectively. At this nucleotide substitution rate, the most recent common ancestor (tMRCA) of 2019-nCoVs appeared about 0.253-0.594 year before the epidemic. Conclusion Our analysis suggests that at least two different viral strains of 2019-nCoV are involved in this outbreak that might occur a few months earlier before it was officially reported.


title: Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge

text: OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. METHODS: The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT) examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [D(L)CO] < 80% of predicted value [pred]) received regular lung function tests and HRCT examinations in the follow-up phase in order to document the changes in their lung condition. Some patients who complained of joint pain were given magnetic resonance imaging (MRI) examinations of their femoral heads. FINDINGS: Of all the subjects, 81.2% (311 of 383 patients) tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients) were suffering from lung diffusion abnormities (D(L)CO < 80% pred) and 21.5% (67 of 311 patients) exhibited lung fibrotic changes. In the 12 month duration of this study, all of the 40 patients with lung diffusion abnormities who were examined exhibited some improvement of lung function and fibrosis detected by radiography. Of the individuals receiving MRI examinations, 23.1% (18 of 78 patients) showed signs of femoral head necrosis. INTERPRETATION: The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.


Détection pré et postopératoire de l’infection virale en cas de chirurgie carcinologique ne pouvant être retardée, pendant la pandémie de COVID-19


title: Predicting contaminant dispersion using modified turbulent Schmidt numbers from different vortex structures

text: Abstract Air pollutant transmission has significant influences on indoor air quality (IAQ). It is crucial to study mechanisms involved with airborne contaminant dispersion indoors. However, relationship between pollutant diffusion coefficient and viscosity in enclosed spaces has not been fully understood. In this study, turbulent Schmidt number (Sc t ) was modified as a function of turbulent kinematic viscosity rather than a constant value to better simulate dispersion of airborne contaminant in two typical enclosed spaces: an aircraft cabin and an office room. An experiment for airborne contaminant transmission was conducted in an aircraft cabin mockup. Combining with experimental data in the office room with an under floor air distribution (UFAD) system from literature, Sc t was modified based on airflow vortex structures. The performance of RNG k-ε model using the modified Sc t was found to be obviously better than that using the default Sc t value in both the two enclosed spaces. In addition, model applicability to different enclosed spaces was analyzed based on the airflow vibration frequency.


title: Diagnosis of human coronavirus infection by immunofluorescence: Method and application to respiratory disease in hospitalized children

text: Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.


title: Chapter 10 Emerging viral infections

text: Abstract The emergence of viral infections is driven by multiple factors including changes in human behavior, population growth, reservoir host distribution, viral diversity and environmental changes. Effective surveillance methods, diagnostic assays and containment measures are pivotal to preventing widespread outbreak of a new viral infection. However, the limited understanding of some emerging viruses poses numerous challenges for effective intervention. In this chapter we discuss various genomics-based methods and strategies to overcome these inherent challenges of emerging and re-emerging viral infections with a focus on current viral threats. We also provide an outlook on the use of genomic tools in personalized medicine and potential solutions to current and foreseeable challenges.


Comment on “Psoriasis, COVID‐19 and acute respiratory distress syndrome: focusing on the risk of concomitant biological treatment”


title: COVID‐19– Are telehealth and tele‐education the answers to keep the ball rolling in Dentistry?

text: Larry David, the co-creator and producer of Seinfeld, when asked by a reporter from the New York Times about what he fears the most while quarantining during the COVID 19 Epidemic, responded "Anarchy and a potential dental emergency - and not necessarily in that order"(Dowd, 2020).The pandemic introduced a new layer of challenges on how to provide care, alleviate pain. Restrictions have been implemented by the majority of governments, as SARS-CoV-2 has been detected in saliva samples and infection typically spread through respiratory droplets (Centers for Disease Control, 2020).


title: A One Health Perspective on the Human–Companion Animal Relationship with Emphasis on Zoonotic Aspects

text: Over time the human–animal bond has been changed. For instance, the role of pets has changed from work animals (protecting houses, catching mice) to animals with a social function, giving companionship. Pets can be important for the physical and mental health of their owners but may also transmit zoonotic infections. The One Health initiative is a worldwide strategy for expanding collaborations in all aspects of health care for humans, animals, and the environment. However, in One Health communications the role of particularly dogs and cats is often underestimated. Objective: Evaluation of positive and negative One Health issues of the human–companion animal relationship with a focus on zoonotic aspects of cats and dogs in industrialized countries. Method: Literature review. Results: Pets undoubtedly have a positive effect on human health, while owners are increasing aware of pet’s health and welfare. The changing attitude of humans with regard to pets and their environment can also lead to negative effects such as changes in feeding practices, extreme breeding, and behavioral problems, and anthropozoonoses. For the human, there may be a higher risk of the transmission of zoonotic infections due to trends such as sleeping with pets, allowing pets to lick the face or wounds, bite accidents, keeping exotic animals, the importation of rescue dogs, and soil contact. Conclusions: One Health issues need frequently re-evaluated as the close human–animal relationship with pet animals can totally differ compared to decennia ago. Because of the changed human–companion animal bond, recommendations regarding responsible pet-ownership, including normal hygienic practices, responsible breeding, feeding, housing, and mental and physical challenges conforming the biology of the animal are required. Education can be performed by vets and physicians as part of the One Health concept.


title: Rhinovirus frequently detected in elderly adults attending an emergency department

text: The general aim was to investigate the burden of respiratory virus illness in a hospital emergency department, during two different epidemic seasons. Consecutive patients attending an emergency department during two study periods (February/March 2009 and 2010) were enrolled using broad inclusion criteria (fever/preceding fever and one of a set of ICD‐9 codes suggestive of respiratory illness); nasopharyngeal washes were tested for the most common respiratory viruses using PCR‐based methods. Influenza A virus was detected in 24% of samples collected in February/March 2009, whereas no samples tested positive for influenza during February/March 2010 (pandemic H1N1 Influenza A having circulated earlier in October–December 2009). Rhinovirus (HRV) was detected in 16% and 8% of patients recruited over the two study periods, respectively. Other respiratory viruses were detected rarely. Patient data were then analyzed with specific PCR results, comparing the HRV‐positive group with virus‐positive and no virus‐detected groups. Individuals over 65 years old with HRV presented with signs, symptoms and underlying conditions and were admitted to hospital as often as the other enrolled patients, mainly for dyspnoea and chronic obstructive pulmonary disease acute exacerbation. Conversely, younger individuals with HRV, although presenting with respiratory signs and symptoms, were generally diagnosed with non‐respiratory conditions. HRV was detected frequently in elderly patients attending the emergency department for respiratory distress without distinguishing clinical features. Molecular diagnosis of lower respiratory tract infections and surveillance of infectious diseases should include tests for HRV, as this virus is associated frequently with hospitalization of the elderly. J. Med. Virol. 83:2043–2047, 2011. © 2011 Wiley‐Liss, Inc.


title: Quantification of the severity of an outbreak in human infection control

text: Summary Background The severity of an outbreak is a priority in decision-making for human infection control. However, there have been no reports on how to quantify the severity of an outbreak. Methods We propose a simple method to measure the severity of an infectious disease outbreak. It involves scoring the severity of clinical signs, the transmission of the infection, the number of cases, and the infection source. Results The method was evaluated using the data available at the early stage of some recent outbreaks of infectious diseases, including the influenza A (H1N1) pandemic in 2009, and the evaluation supports the design idea. Conclusion The method is practical for rating the severity of an infectious disease outbreak, though it should be optimized. It could also be used to judge whether an event constitutes a public health emergency of international concern (PHEIC) or not.


title: High-titer preparation of Bombyx mori nucleopolyhedrovirus (BmNPV) displaying recombinant protein in silkworm larvae by size exclusion chromatography and its characterization

text: BACKGROUND: Budded baculoviruses are utilized for vaccine, the production of antibody and functional analysis of transmembrane proteins. In this study, we tried to produce and purify the recombinant Bombyx mori nucleopolyhedrovirus (rBmNPV-hPRR) that displayed human (pro)renin receptor (hPRR) connected with FLAG peptide sequence on its own surface. These particles were used for further binding analysis of hPRR to human prorenin. The rBmNPV-hPRR was produced in silkworm larvae and purified from its hemolymph using size exclusion chromatography (SEC). RESULTS: A rapid method of BmNPV titer determination in hemolymph was performed using quantitative real-time PCR (Q-PCR). A correlation coefficient of BmNPV determination between end-point dilution and Q-PCR methods was found to be 0.99. rBmNPV-hPRR bacmid-injected silkworm larvae produced recombinant baculovirus of 1.31 × 10(8 )plaque forming unit (pfu) in hemolymph, which was 2.8 × 10(4 )times higher than transfection solution in Bm5 cells. Its purification yield by Sephacryl S-1000 SF column chromatography was 264 fold from larval hemolymph at 4 days post-injection (p.i.), but 35 or 39 fold at 4.5 or 5 days p.i., respectively. Protein patterns of rBmNPV-hPRR purified at 4 and 5 days were the same and ratio of envelope proteins (76, 45 and 35 kDa) to VP39, one of nucleocapsid proteins, increased at 5 days p.i. hPRR was detected in only purified rBmNPV-hPRR at 5 days p.i.. CONCLUSION: The successful purification of rBmNPV-hPRR indicates that baculovirus production using silkworm larvae and its purification from hemolymph by Sephacryl S-1000 SF column chromatography can provide an economical approach in obtaining the purified BmNPV stocks with high titer for large-scale production of hPRR. Also, it can be utilized for further binding analysis and screening of inhibitors of hPRR.


title: Bayesian modelling of an epidemic of severe acute respiratory syndrome

text: This paper analyses data arising from a SARS epidemic in Shanxi province of China involving a total of 354 people infected with SARS-CoV between late February and late May 2003. Using Bayesian inference, we have estimated critical epidemiological determinants. The estimated mean incubation period was 5.3 days (95% CI 4.2–6.8 days), mean time to hospitalisation was 3.5 days (95% CI 2.8–3.6 days), mean time from symptom onset to recovery was 26 days (95% CI 25–27 days) and mean time from symptom onset to death was 21 days (95% CI 16–26 days). The reproduction ratio was estimated to be 4.8 (95% CI 2.2–8.8) in the early part of the epidemic (February and March 2003) reducing to 0.75 (95% CI 0.65–0.85) in the later part of the epidemic (April and May 2003). The infectivity of symptomatic SARS cases in hospital and in the community was estimated. Community SARS cases caused transmission to others at an estimated rate of 0.4 per infective per day during the early part of the epidemic, reducing to 0.2 in the later part of the epidemic. For hospitalised patients, the daily infectivity was approximately 0.15 early in the epidemic, but fell to 0.0006 in the later part of the epidemic. Despite the lower daily infectivity level for hospitalised patients, the long duration of the hospitalisation led to a greater number of transmissions within hospitals compared with the community in the early part of the epidemic, as estimated by this study. This study investigated the individual infectivity profile during the symptomatic period, with an estimated peak infectivity on the ninth symptomatic day.


title: Using Grounded Theory to Inform the Human-Centered Design of Digital Health in Geriatric Palliative Care

text: CONTEXT: Digital health offers innovative mechanisms to engage in palliative care, yet digital systems are typically designed for individual users, rather than integrating the patient’s caregiving “social convoy” (i.e. family members, friends, neighbors, formal caregiving supports) to maximize benefit. As older adults with serious illness increasingly rely on the support of others, there is a need to foster effective integration of the social convoy in digitally supported palliative care. OBJECTIVES: Conduct a qualitative study examining patient, social convoy, and health care provider perspectives on digital health for palliative care to inform the design of future digital solutions for older adults with serious illness and their social convoy. METHODS: Grounded theory approach using semi-structured interviews (N=81) with interprofessional health care providers, older adults with serious illness, and their social convoy participants at home, clinic, or Zoom. Interviews were conducted using question guides relevant to the participant group and audio recorded for verbatim transcription. Two coders lead the inductive analysis using open and axial coding. RESULTS: Thematic results aligned with the human centered design framework, which is a participatory approach to the design process that incorporates multiple user stakeholders to develop health solutions. The human centered design process and corresponding theme included: (1) Empathy: Patient, Caregiver, and Provider Experience reports participants’ experience with managing serious illness, caregiving, social support, and technology use. (2) Define: Reactions to Evidence-Based Care Concepts and Barriers illustrates participants’ perspectives on the domains of palliative care ranging from symptom management to psychosocial-spiritual care. (3) Ideation: Desired Features reports participant recommendations for designing digital health tools for palliative care domains. CONCLUSION: Digital health provides an opportunity to expand the reach of geriatric palliative care interventions. This paper documents human centered preferences of geriatric palliative care digital health to ensure technologies are relevant and meaningful to health care providers, patients, and the caregiving social convoy.


title: The molecular structure of 4-methylpyridine-N-oxide: Gas-phase electron diffraction and quantum chemical calculations

text: Abstract The molecular structure of 4-methylpiridine-N-oxide, 4-MePyO, has been studied by gas-phase electron diffraction monitored by mass spectrometry (GED/MS) and quantum chemical (DFT) calculations. Both, quantum chemistry and GED analyses resulted in C S molecular symmetry with the planar pyridine ring. Obtained molecular parameters confirm the hyperconjugation in the pyridine ring and the sp2 hybridization concept of the nitrogen and carbon atoms in the ring. The experimental geometric parameters are in a good agreement with the parameters for non-substituted N-oxide and reproduced very closely by DFT calculations. The presence of the electron-donating CH3 substituent in 4-MePyO leads to a decrease of the ipso-angle and to an increase of r(N→O) in comparison with the non-substituted PyO. Electron density distribution analysis has been performed in terms of natural bond orbitals (NBO) scheme. The nature of the semipolar N→O bond is discussed.


title: Sequencing B cell receptors from ferrets (Mustela putorius furo)

text: The domestic ferret (Mustela putorius furo) provides a critical animal model to study human respiratory diseases. However immunological insights are restricted due to a lack of ferret-specific reagents and limited genetic information about ferret B and T cell receptors. Here, variable, diversity and joining genes within the ferret kappa, lambda and heavy chain immunoglobulin loci were annotated using available genomic information. A multiplex PCR approach was derived that facilitated the recovery of paired heavy and light chain immunoglobulin sequences from single sorted ferret B cells, allowing validation of predicted germline gene sequences and the identification of putative novel germlines. Eukaryotic expression vectors were developed that enabled the generation of recombinant ferret monoclonal antibodies. This work advances the ferret as an informative immunological model for viral diseases by allowing the in-depth interrogation of antibody-based immunity.


title: Rapid review protocol: zinc for the prevention or treatment of COVID-19 and other coronavirus-related respiratory tract infections

text: Abstract Background . The global COVID-19 pandemic has prompted an urgent search for effective interventions. SARS-CoV-2 mortality/morbidity risk increases with age and for those chronic disease co-morbidities, both of which are associated with lower zinc status, as is the risk of infection. Methods Rapid review methods will be applied to a systematic review of zinc for the prevention or treatment of SARS-CoV-2 and viral respiratory tract infections in humans. Included are published studies reporting randomised and quasi-randomised controlled trials that compare zinc intervention to placebo and/or other comparator interventions. English and Chinese language databases will be searched for primary studies of viral respiratory tract infections and clinical trial registries for SARS-CoV-2 infections. Due to concerns about indirectness, studies evaluating non-SARS-CoV-2 coronavirus infections will be rated down by one level, and non-specific or confirmed non-coronavirus viral infections will be rated down by two levels. Review constraints include 1) using Google translate when screening articles published in languages other than English or Chinese and limited translation 2) following calibration, only one reviewer will screen articles, extract data, appraise quality and conduct the analysis, 3) prioritising data extraction and meta-analyses of SARS-CoV-2 studies and critical outcomes of other viral infections, followed by high risk groups and 4) reporting important preliminary findings prior to peer review if necessary. Discussion . The application of these rapid review methods and broadening the inclusion criteria to include other coronavirus-related viral respiratory tract infections aims to enable a timely evidence appraisal of priority research questions and dissemination of results.


title: Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012–2015

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology.


title: The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species

text: The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.


title: Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness

text: RATIONALE: Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. OBJECTIVE: Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. SETTING: 6 major hospitals in 2 districts of Beijing, China. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: 245 index cases with ILI. INTERVENTION: Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). MAIN OUTCOME MEASURE: Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. RESULTS: In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. CONCLUSIONS: The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. TRIAL REGISTRATION NUMBER: ACTRN12613000852752; Results.


title: Magnetic Beads‐Based Electrochemical Sensors Applied to the Detection and Quantification of Bioterrorism/Biohazard Agents

text: Nowadays, detecting the presence of bioterrorism and biohazard agents in environmental and food samples is of great concern, due to their toxicity, and because many of them are prone to be used in terrorism attacks. The use of functionalized magnetic beads (MBs) in the development of electrochemical immuno‐ and genosensors has resulted in innovative and powerful detection strategies that may be applied to environmental, food and clinical analysis. This review describes current research on the combination of functionalized MBs with electrochemical detection for the development of magnetobiosensors applied to rapid, sensitive and specific detection of bioterrorism and biohazard agents.


title: Bioinformatics studies on a function of the SARS-CoV-2 spike glycoprotein as the binding of host sialic acid glycans

text: SARS-CoV and SARS-CoV-2 do not appear to have functions of a hemagglutinin and neuraminidase. This is a mystery, because sugar binding activities appear essential to many other viruses including influenza and even most other coronaviruses in order to bind to and escape from the glycans (sugars, oligosaccharides or polysaccharides) characteristic of cell surfaces and saliva and mucin. The S1 N terminal Domains (S1-NTD) of the spike protein, largely responsible for the bulk of the characteristic knobs at the end of the spikes of SARS-CoV and SARS-CoV-2, are here predicted to be “hiding” sites for recognizing and binding glycans containing sialic acid. This may be important for infection and the ability of the virus to locate ACE2 as its known main host cell surface receptor, and if so it becomes a pharmaceutical target. It might even open up the possibility of an alternative receptor to ACE2. The prediction method developed, which uses amino acid residue sequence alone to predict domains or proteins that bind to sialic acids, is naïve, and will be advanced in future work. Nonetheless, it was surprising that such a very simple approach was so useful, and it can easily be reproduced in a very few lines of computer program to help make quick comparisons between SARS-CoV-2 sequences and to consider the effects of viral mutations.


title: Practical Guide for Pediatric Pulmonologists on Imaging Management of Pediatric Patients with COVID‐19

text: Understanding of coronavirus disease 2019 is rapidly evolving with new articles on the subject daily. This flood of articles can be overwhelming for busy practicing clinicians looking for key pieces of information that can be applied in daily practice. This review article synthesizes the reported imaging findings in pediatric COVID‐19 across the literature, offers imaging differential diagnostic considerations and useful radiographic features to help differentiate these entities from COVID‐19, and provides recommendations for ordering imaging studies to evaluate suspected cases of pediatric COVID‐19. This article is protected by copyright. All rights reserved.


title: Discovery of novel astrovirus and calicivirus identified in ruddy turnstones in Brazil

text: Birds are the natural reservoir of viruses with zoonotic potential, as well as contributing to the evolution, emergence, and dissemination of novel viruses. In this study, we applied a high-throughput screening approach to identify the diversity of viruses in 118 samples of birds captured between October 2006 to October 2010 in the North and Northeast regions of Brazil. We found nearly complete genomes of novel species of astrovirus and calicivirus in cloacal swabs of ruddy turnstones (Arenaria interpres) collected in Coroa do Avião islet, Pernambuco State. These viruses are positive-sense single-stranded RNA with a genome of ~7 to 8 kb, and were designated as Ruddy turnstone astrovirus (RtAstV) and Ruddy turnstone calicivirus (RTCV), respectively. Phylogenetic analysis showed that RtAstV and RTCV grouped in a monophyletic clade with viruses identified from poultry samples (i.e., chicken, goose, and turkey), including viruses associated with acute nephritis in chickens. Attempts of viral propagation in monkey and chicken cell lines for both viruses were unsuccessful. Also, we found genomes related with viral families that infect invertebrates and plants, suggesting that they might be ingested in the birds’ diet. In sum, these findings shed new light on the diversity of viruses in migratory birds with the notable characterization of a novel astrovirus and calicivirus.


title: The COVID-19 & Cancer Consortium (CCC19): a collaborative effort to understand the effects of COVID-19 on patients with cancer

text: Summary National and international consortia will play a key role in understanding the effects of the coronavirus disease 2019 (COVID-19) pandemic on cancer patients. The COVID-19 & Cancer Consortium (CCC19) aims to collect and analyze observational data at scale to inform clinical practice in real-time.


title: Impact of reduction in contact time activity of infected individuals on the dynamics and control of directly transmitted respiratory infections in SIR models

text: This paper aims to study the impact of using an educational strategy on reducing the efforts needed to control respiratory transmitted infections represented by SIR models, taking into account heterogeneity in contacts between infected and non-infected individuals. Therefore, a new incidence function, in which the difference in contact time activity between infected and non-infected individuals is taken into account, is formulated. Equilibrium and stability analyses of the model have been carried out. The model has been extended to include the effect of herd immunity and the analysis showed that the higher the percent reduction [Formula: see text] in the contact-activity time of infected individuals is, the lower the critical vaccination coverage level [Formula: see text] required to eliminate the infection is, and therefore, the lower the infection’s minimum elimination effort is. Another extension of the basic model to include a control strategy based on treating infected individuals at rate α with a maximum capacity treatment [Formula: see text] has been considered. The equilibrium analysis showed the existence of multiple subcritical and supercritical endemic equilibria, while the stability analysis showed that the model exhibits a Hopf bifurcation. Simulations showed that the higher the maximum treatment capacity [Formula: see text] is, the lower the value of the critical reduction in infected individuals’ time activity [Formula: see text] , at which a Hopf bifurcation is generated, is. Simulations with parameter values corresponding to the case of influenza A have been carried out.


title: Milk-derived antimicrobial peptides to protect against Neonatal Diarrheal Disease: An alternative to antibiotics

text: Abstract Neonatal Diarrheal Disease is responsible for significant economic losses to the livestock industries in Canada and around the world. Microbes responsible are diverse and include Escherichia coli, Salmonella, Rotavirus, Coronavirus and Cryptosporidia. While the use of antibiotics as a treatment for bacterial infections and as a prophylactic additive in feed has dramatically improved cattle production in recent decades, the increasing pressure to reduce or eliminate use of antibiotics in animals has caused the livestock industry to seek appropriate alternatives. Antimicrobial/Host Defense Peptides are natural compounds present on skin and in secretions in plants and animals that are microbicidal for bacteria, viruses, and parasites and they stimulate the immune system to combat infectious diseases. Our objective is to establish orally-obtained Host Defense Peptides (HDPs) as an alternative to antibiotics to protect against Neonatal Diarrheal Disease in calves. We devised a method to allow the cow udder to act as a factory to produce HDPs so that suckling calves will receive a continuous oral dose of HDPs over several weeks to protect them against neonatal diarrhea. We will use Adenovirus to deliver a gene coding for several HDPs in-frame into mammary epithelial cells. The epithelial cells will secrete the HDP protein into milk to be consumed by the suckling calves and trypsin in the calf gut will release the HDPs through cleavage. Thus, the novelty of this research lies not only in the proposed alternative to antibiotics to protect neonates against disease, but in the method by which we introduce the peptides to the suckling offspring.


title: Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

text: Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARS‐CoV. Pulmonary involvement is the dominant clinical feature but extra‐pulmonary manifestations are also common. Factors that account for the wide spectrum of organ system involvement and disease severity are poorly understood and the pathogenesis of SARS‐CoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARS‐CoV. Studies of the tissue and cellular distribution of SARS‐CoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. ACE2 is expressed at high level in the primary target cells of SARS‐CoV, namely pneumocytes and surface enterocytes of the small intestine. Despite the fact that SARS‐CoV can infect the lung and intestine, the tissue responses in these two organs are different. All other tissues and cell types expressing ACE2 may be potential targets of SARS‐CoV infection. Remarkably, endothelial cells, which express ACE2 to a high level, have not been shown to be infected by SARS‐CoV. There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. Therefore, other virus receptors or co‐receptors may be required in different tissues. Moreover, the interaction between SARS‐CoV and the immunological or lymphoid system remains to be defined. It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. As our knowledge of the pathogenic mechanisms improves, a more rational approach to therapeutic and vaccine development can be designed in order to combat this new and fatal human disease. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: 5 An Analysis of Demographic and Behavior Trends Using Social Media: Facebook, Twitter, and Instagram

text: Abstract Personality and character have major effects on certain behavioral outcomes. As advancements in technology occur, more people these days are using social media such as Facebook, Twitter, and Instagram. Due to the increase in social media's popularity, the types of behaviors are now easier to group and study as this is important to know the behavior of users via social networking in order to analyze similarities of certain behavior types and this can be used to predict what they post as well as what they comment, share, and like on social networking sites. However, very few review studies have undertaken grouping according to similarities and differences to predict the personality and behavior of individuals with the help of social networking sites such as Facebook, Twitter, and Instagram. Therefore, the purpose of this research is to collect data from previous researches and to analyze the methods they have used. This chapter reviewed 30 research studies on the topic of behavioral analysis using the social media from 2015 to 2017. This research is based on the method of previous publications and analyzed the results, limitations, and number of users to draw conclusions. Our results indicated that the percentage of completed research on the Facebook, Twitter, and Instagram show that 50% of the studies were done on Twitter, 27% on Facebook, and 23% on Instagram. Twitter seems to be more popular and recent than the other two spheres as there are more studies on it. Further, we extracted the studies based on the year and graphs in 2015 which indicated that more research has been done on Facebook to analyze the behavior of users and the trends are decreasing in the following year. However, more studies have been done on Twitter in 2016 than any other social media. The results also show the classifications based on different methods to analyze individual behavior. However, most of the studies have been done on Twitter, as it is more popular and newer than Facebook and Instagram particularly from 2015 to 2017, and more research needs to be done on other social media spheres in order to analyze the trending behaviors of users. This study should be useful to obtain knowledge about the methods used to analyze user behavior with description, limitations, and results. Although some researchers collect demographic information on users’ gender on Facebook, others on Twitter do not. This lack of demographic data, which is typically available in more traditional sources such as surveys, has created a new focus on developing methods to work out these traits as a means of expanding Big Data research.


title: Protest tegen protest

text: DENVER, VS - Deze verpleegkundige probeert samen met collega-zorgverleners demonstrerende automobilisten tegen te houden. De demonstranten togen eind april naar de regeringsgebouwen in Denver, Colorado, omdat ze het niet eens waren met de lockdown die de staat had opgelegd. Fotograaf Alyson McClaran vertelt dat deze verpleegkundige alle kalmte bewaarde terwijl demonstranten hatelijke leuzen naar hem riepen, zoals ‘Amerika is het land van de vrijheid, ga naar China als je communisme wil.’ Medio mei waren er al zo’n 85.000 Amerikanen overleden aan covid-19.


title: Daycaritis

text: Healthy infants and toddlers who attend day care centers are at increased risk for contracting common childhood illnesses such as viral upper and lower respiratory illnesses, viral gastrointestinal infections, and acute and chronic otitis media. The author proposes that this high frequency of common infections be termed daycaritis. Daycaritis imposes significant social and economic burdens on both the family and the health care system. This review describes the most common infections seen in day care attendees, preventative measures to decrease the rates of illness, and a practical approach to diagnosis and management in the emergency department.


title: Responding to COVID‐19: How to Navigate a Public Health Emergency Legally and Ethically

text: Few novel or emerging infectious diseases have posed such vital ethical challenges so quickly and dramatically as the novel coronavirus SARS‐CoV‐2. The World Health Organization declared a public health emergency of international concern and recently classified COVID‐19 as a worldwide pandemic. As of this writing, the epidemic has not yet peaked in the United States, but community transmission is widespread. President Trump declared a national emergency as fifty governors declared state emergencies. In the coming weeks, hospitals will become overrun, stretched to their capacities. When the health system becomes stretched beyond capacity, how can we ethically allocate scarce health goods and services? How can we ensure that marginalized populations can access the care they need? What ethical duties do we owe to vulnerable people separated from their families and communities? And how do we ethically and legally balance public health with civil liberties?


title: Membrane and Phospholipid Binding by Murine Coronaviral Nucleocapsid N Protein

text: Abstract Evidence is presented which indicates that membrane binding of the murine coronavirus, mouse hepatitis virus (MHV) nucleocapsid (N) protein is mediated by certain lipids. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show datectable binding. Binding occurs with both free and nucleocapsid-associated N protein, arguing for membrane-binding sites on the N protein itself, rather than on RNA. Binding of N protein also occurs to membranes in the absence of MHV matrix (M) protein which is known to interact with the N protein. Both non-viral, single-stranded RNA and DNA inhibit membrane binding of N protein. In addition, purified phospholipid liposomes compete against N protein binding to membranes. Of various phospholipids tested, cardiolipin was the most effective in inhibiting membrane binding. The N protein was also shown to bind directly to phospholipid liposomes containing cardiolipin as well as to liposomes containing total lipids extracted from mouse L-2 cells. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly. Most interestingly the properties of phospholipid and nucleic acid binding are markedly similar to those recently described for the bacterial DNA-binding proteins DnaA and recA.


title: Epidemiological, clinical and genotypic features of human Metapneumovirus in patients with influenza-like illness in Senegal, 2012 to 2016

text: BACKGROUND: Human metapneumovirus (HMPV) is a causal agent of acute respiratory infection, especially in primarily children. At the clinical level, HMPV is associated to several diseases including bronchitis, croup, pneumonia, bronchiolitis, reactive airway disease, chronic obstructive pulmonary disease and asthma exacerbations, specifically in children less than 5 years. Here, we carried out a retrospective pilot study, based on the processing of nasopharyngeal swabs, with a focus on the epidemiology and molecular characteristics of HMPV in Senegal. METHODS: This retrospective study was conducted from January 2012 to December 2016. Briefly, all outpatients presenting to healthcare sentinel sites were screened for surveillance enrollment and included if they met criteria for ILI. Naso-oropharyngeal swabs were collected from eligible participants. For viral respiratory pathogens detection, including HMPV, the Anyplex™ II RV16 Detection kit was used. A fragment of the hMPV F gene was targeted for sequencing. RESULTS: In total, 8209 patients with ILI were enrolled. Half of them (49.7%) were children under 5 years. Fever was the most common symptom followed by cough, and rhinitis. Three hundred eight patients were positive for HMPV (3.75%). 89 (28.9%) were detected as single infection. In co-infection cases, the most common co-infecting viruses were influenza, adenovirus and rhinovirus. HMPV detection rates in the different age groups varied significantly with the children under 5 years group accounting for 71.7% of positive patients. The temporal distribution pattern for HMPV infection showed a clear seasonal pattern with a higher activity during the rainy period (July–September). Phylogenetic analyses revealed that HMPV specimens circulating in Senegal were distributed into the two main genetic lineages, A and B. We also noted a co-circulation of both genetic lineages during the whole study period except in 2014. CONCLUSION: In summary, the present study characterized the recent prevalence, seasonality and genetic diversity of HMPV in a large outpatient population presented with ILI in Senegal between 2012 and 2016. Globally our results show a clear seasonal circulation pattern of HMPV in Senegal. Our findings identified children less than 5 years as more susceptible group to HMPV infection. Molecular studies identified A2, B1 and B2 as the major genotypes circulating.


title: Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4(+) and CD8(+) T cells promote cellular immune responses

text: Cellular immune response plays an important role in antiviral immunity. In our previous study, immunization of mice with severe acute respiratory syndrome coronavirus (SARS CoV) spike (S) DNA vaccine could induce both humoral and cellular immunity in response to a pool of entire overlapping S peptides. Identification of functional dominant epitopes in SARS CoV S protein for T cells is crucial for further understanding of cellular immune responses elicited by SARS CoV S DNA vaccine. In present study, mice were immunized with SARS CoV S DNA vaccine. Subsequently, a pool of 17–19 mers overlapped SARS CoV S peptides, which served as immunogens, were scanned to identify the specific epitopes for T cells. Two H-2(d) restricted CD4(+) T epitopes, N60 (S435–444) and P152 (S1111–1127), and two H-2(d) restricted CD8(+) T cell epitopes, N50 (S365–374) and P141 (S1031–1047) were identified by three different methods, enzyme-linked immunosorbent assay (ELISA), enzyme linked immunospot assay (ELISPOT) and fluorescence activated cell sorter (FACS). The dominant CD4(+) T cell epitope (N60) and CD8(+) T cell epitope (N50) located in the receptor-binding domain (RBD) of SARS CoV S protein, which mediated virus combining and fusing to susceptible cells. Importantly, our novel finding is that mice primed with SARS S DNA vaccine and boosted with T cell epitopes (N50 and N60) could promote antigen specific CD4(+) and CD8(+) T cell immune responses. Our study provides valuable information for the design of vaccine for SARS study.


title: WHO informal consultation on the guidelines for evaluation of the quality, safety, and efficacy of DNA vaccines, Geneva, Switzerland, December 2019

text: Consultations have been held to promote the revision of the WHO guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines adopted by the Expert Committee on Biological Standardization (ECBS) in 2005. The drivers for this revision are described, including the need for regulatory convergence highlighted by the WHO R&D Blueprint. These consultations have driven the revision to its current form, where a new guideline that includes quality, nonclinical, and clinical evaluation of plasmid DNA vaccines is being prepared for public consultation with a view to present to an upcoming ECBS. Major changes to the guidelines include streamlining the existing quality (part A) and nonclinical (part B) sections to reflect the two decades of experience, with manufacturing and control, nonclinical evaluation, and clinical testing of plasmid DNA vaccines, as a platform technology. The urgency for gaining regulatory convergence on this topic is that development of such a platform technology as DNA vaccines for routine use immunizations will prepare manufacturers and regulators across the globe in dealing with rapid development of medical countermeasures against emerging infectious diseases even in the face of an emergency setting. Two examples are described of Zika candidate vaccines that have rapidly advanced in development based on preexisting nonclinical and clinical data that precluded the need to repeat nonclinical toxicology. This report describes the progress stemming from the most recent consultation on the guidelines, including topics discussed and consensus reached.


title: The role of a Coronavirus disease 2019 pharmacist: an Australian perspective

text: The coronavirus disease 2019 (COVID-19) pandemic has greatly impacted healthcare services around the world. Pharmacists are front-line healthcare professionals and integral members of the healthcare team. The deployment of a specialized ‘COVID pharmacist’ within our institution has demonstrated that the skills of the pharmacist can be adapted, expanded and utilized to alleviate the pressure of doctor shortages, reduce healthcare worker exposure to infected patients, contribute to therapeutic decisions and work collaboratively to tackle the challenges faced during this pandemic. This commentary details an Australian hospital pharmacy response to the COVID-19 pandemic, describing the unique clinical and practical contributions made by a specialized COVID pharmacist in our institution.


Employing dermatologists on the frontline against COVID‐19: All hands on deck


title: Accommodation of large cargo within Golgi cisternae

text: In mammalian cells, the Golgi complex has an elaborate structure consisting of stacked, flattened cisternal membranes collected into a ribbon in the center of the cell. Amazingly, the flattened cisternae can rapidly dilate to accommodate large cargo as it traffics through the organelle. The mechanism by which this occurs is unknown. Exocytosis of large cargo is essential for many physiological processes, including collagen and lipoprotein secretion, and defects in the process lead to disease. In addition, enveloped viruses that bud into the endoplasmic reticulum or Golgi complex must also be transported through Golgi cisternae for secretion from the infected cell. This review summarizes our understanding of intra-Golgi transport of large cargo, and outlines current questions open for experimentation.


Mitigating mental health consequences during the COVID‐19 outbreak: Lessons from China


title: Community-acquired pneumonia: An overview

text: Community-acquired pneumonia is still a significant cause of morbidity and mortality and is often misdiagnosed and inappropriately treated. Although it can be caused by a wide variety of micro-organisms, the pneumococcus, atypicals, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, Staphylococcus aureus and certain Gram-negative rods are the usual pathogens encountered. The site-of-care decision is critical in determining the site and type of care as well as the extent of diagnostic workup. Antimicrobial therapy should be started as soon as possible particularly in those requiring admission to hospital, but typically the physician does not know with any degree of certainty the identity of the etiologic pathogen. A number of national guidelines have been published to help the physician with this choice. The initial drug(s) can be modified if necessary if the pathogen and its antimicrobial susceptibility pattern becomes known. Adjunctive therapy such as pressors and fluid replacement are of value and macrolides appear to help as well, likely secondary to their immunomodulatory effects. Recent data also suggest a role for steroids.


title: Comparison of multiplexed-tandem real-time PCR panel with reference real-time PCR molecular diagnostic assays for detection of Giardia intestinalis and Tritrichomonas foetus in cats

text: Abstract Giardia intestinalis and Tritrichomonas foetus are frequent enteric protozoan parasites of the gastrointestinal track of domestic cats. Because of different treatment options for the parasites, confirmation of presence of one or both pathogens is necessary. The PCR based assays are suitable for differential diagnosis. We evaluated the performance of Small Animal Diarrhoea panel, a multiplexed-tandem real-time PCR (MT-PCR) assay, that detects DNA of both G. intestinalis and T. foetus. The sensitivity and specificity were compared to reference real-time PCR assays using 105 faecal samples, 39.05% (n = 41) positive for G. intestinalis and 30.48% (n = 32) were positive for T. foetus. The faecal samples positive for T. foetus had a high proportion of late amplifiers, determined by an arbitrary threshold of Ct-values > 35. On the other hand, only one G. intestinalis positive sample was considered a late amplifier. For G. intestinalis DNA, the MT-PCR assay had 95.1% sensitivity and 92.1% specificity. For T. foetus DNA, the MT-PCR assay had 41.9% sensitivity and 100.0% specificity. To evaluate the interlaboratory reproducibility of the MT-PCR assay, results were compared in two different laboratories and found to be in a very good agreement (Kappa = 0.9). Further analysis of the DNA using conventional PCR determined presence of G. intestinalis Assemblage F and T. foetus genotype ‘feline’. In conclusion, the MT-PCR Small Animal Diarrhoea panel had a good and poor performance against reference assays for G. intestinalis and T. foetus, respectively. The assay is suitable for detection and differential diagnosis of G. intestinalis and moderate to high burdens of T. foetus in small animal clinical practice.


title: Molecular epidemiology of influenza B virus among hospitalized pediatric patients in Northern Italy during the 2015-16 season

text: BACKGROUND: The influenza B viruses belong to two lineages distinguished by their genetic and antigenic characteristics, which are referred to as the Yamagata and Victoria lineages, designated after their original isolates, B/Yamagata/16/88 and B/Victoria/2/87. The primary aim of this study was to evaluate the molecular characteristics of influenza B viruses circulating in a region of Northern Italy, Lombardia, during the influenza season of 2015–2016. METHODS: Influenza B virus was detected using a respiratory virus panel of assays and an influenza B-specific real-time polymerase chain reaction. The complete influenza B hemagglutinin (HA) gene was amplified and sequenced directly from clinical specimens. Phylogenetic analysis was performed using nucleotide sequences. RESULTS: A total of 71 hospitalized pediatric patients were influenza B positive. Phylogenetic analysis showed that the great majority of influenza B strains (66/71, 93.0%) belonged to the Victoria-lineage and were antigenically like vaccine strain (B/Brisbane/60/2008) included only in the quadrivalent vaccine. In the detected influenza B strains, a series of amino acid changes were observed in the antigenic regions: I117V, V124A, N129D, V146I, N197D, T199A, and A202T. However, only 2 amino acid changes were observed in the HA regions involved in receptor binding or in antibody recognition. CONCLUSIONS: All the influenza B strains identified in this study belonged to the influenza B Victoria lineage not included in the trivalent vaccine commonly used by the general population during the 2015–2016 influenza season in Italy. This indicates that protection against influenza B infection in the vaccinated population was in general very poor during the 2015–2016 influenza season.


title: Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements

text: OBJECTIVES: The molecular mechanisms underlying the pathogenesis of human coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. METHODS: HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. RESULTS: The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways.


Why not to use colchicine in COVID-19? An old anti-inflammatory drug for a novel auto-inflammatory disease


title: Transcriptional slippage occurs during elongation at runs of adenine or thymine in Escherichia coli.

text: A run of 11 adenine or thymine residues at the 5' end of an out-of-frame lacZ gene causes a high level of beta-galactosidase expression in E. coli. This effect was not observed for a run of guanine residues. Reverse transcription of mRNA isolated from E. coli containing the run of 11 A's reveals heterogeneity of transcript length while reverse transcription of mRNA isolated from S. cerevisiae containing the same gene shows no heterogeneity. Protein sequencing of the beta-galactosidase molecules derived from the out-of-frame construct containing a run of adenines reveals the addition of a lysine at the run. A new method was developed where messages small enough to allow resolution of single nucleotide differences on an acrylamide gel are electrophoresed, electroblotted onto nylon and probed. This confirmed the reverse transcription results and showed that additional residues can be added to transcripts derived from DNA containing 10 or 11 thymine residues. A mechanism for slippage is discussed where the A-U rich RNA-DNA hybrid can denature during elongation and rehybridize in an offset position, causing the addition of extra residues to the transcript.


title: Fibrinolytic components in nasal mucosa and nasal secretion

text: We evaluated a possible role for fibrinolytic components in nasal secretion by tissue localization with immunohistochemical techniques and by measuring their antigen concentrations in nasal discharge by means of ELISA and fibrin autography. Nasal mucosa was obtained surgically from the inferior turbinate. Urokinase-type plasminogen activator (u-PA) specific staining was observed in pseudostratified ciliated epithelium and was predominant in mucous cells of the seromucinous gland, while serous cells were almost devoid of stain. The pattern of staining of plasminogen activator inhibitor-2 was similar to that of u-PA. In contrast, plasminogen activator inhibitor-1(PAI-1) immunoreactive material was localized exclusively in serous cells of seromucinous glands. Positive staining for tissue-type plasminogen activator (t-PA) was observed in endothelial cells and basal cells, which differentiate into either ciliated or goblet cells. Nasal secretions were partially fractionated by immunospecific antibody-immobilized Sepharose. Subsequent fibrin autography patterns indicated the presence of u-PA, PAI-1, and t-PA. After methacholine provocation, the level of t-PA increased transiently but decreased rapidly with subsequent challenges. These differential stainings of fibrinolytic components and the existence of PAs and PAI-1 in the nasal discharge suggest that the fibrinolytic system may play a role in the movement and fluidity of nasal secretion.


title: Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

text: BACKGROUND: Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. METHODS: A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. RESULTS: A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). CONCLUSION: The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.


title: The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors

text: Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.


title: Letter to the Editor: Three cases of re‐detectable positive SARS‐CoV‐2 RNA in recovered COVID‐19 patients with antibodies

text: The number of hospitalized cases has declined significantly in Wuhan. However, there have been reports that several cases of re‐detectable positive SARS‐CoV‐2 RNA in recovered COVID‐19 patients, the potential reasons of re‐detectable positive patients remained elusive. Here, we report three confirmed cases of COVID‐19 whose IgM was negative and IgG was positive before the first discharge, while nasopharyngeal swab test of SARS‐CoV‐2 RNA turned positive again during hotel isolation. In addition, all three cases presented negative results for IgM antibodies and positive results for IgG antibodies during re‐admission period. These cases suggested that the reasons for re‐detectable positive patients with profile of antibodies may be related to several factors. It is necessary to quarantine COVID‐19 patients for 14 days after discharge, and the role of antibodies in anti‐SARS‐CoV‐2 warrants further investigation. This article is protected by copyright. All rights reserved.


title: COVID-19 Fear in Eastern Europe: Validation of the Fear of COVID-19 Scale

text: COVID-19 is a major source of fear, stress, and anxiety as well as a major factor impacting the health and wellbeing of people worldwide. The present study builds on the recently developed “Fear of COVID-19 Scale” (Ahorsu et al., In International Journal of Mental Health and Addiction, 10.1007/s11469-020-00270-8, 2020). The sample comprised of 850 participants, male and female young adults from Russia and Belarus. The majority of survey participants are university students and graduates. Females, students, and others from Russia report higher levels of COVID-19-related fear than those from Belarus. Respondents from Russia and Belarus report less fear than people from Iran who were surveyed earlier. The scale used for the present survey evidenced a good Cronbach’s Alpha measure of internal consistency or reliability (0.809). Clearly, further research is needed across locations and over time about the nature and extent of fear caused by COVID 19. Overall, the FCV-19S appears to be a valuable and brief instrument that may provide useful information for intervention and policy purposes to migrate fear and problem behavior linked to infectious disease outbreaks.


title: Temporal and spatial evolution of online public sentiment on emergencies

text: Abstract The transmission of online emergency information has become an active means of expressing public opinion and has vitally affected societal emergency response techniques. This paper analyzes interactions between three groups in time and space using a classic SIR (susceptible, infected, and recovered) epidemic model. Through social network theory and analog simulation analysis, we utilize data from China's Sina Weibo (a popular social media platform) to conduct empirical research on 101 major incidents in China that occurred between 2010 and 2017. We divide these emergencies into four types—natural disasters, accidents, public health events, and social security events—and conduct a simulation using three examples from each group. The results show that government control of public opinion is both cheaper and more effective when it occurs at the initial stages of an incident. By cooperating with the government, the media can facilitate emergency management. Finally, if netizens trust the government and the media, they are more likely to make cooperative decisions, maintain interest, and improve the management of online public sentiment.


title: epicontacts: Handling, visualisation and analysis of epidemiological contacts

text: Epidemiological outbreak data is often captured in line list and contact format to facilitate contact tracing for outbreak control. epicontacts is an R package that provides a unique data structure for combining these data into a single object in order to facilitate more efficient visualisation and analysis. The package incorporates interactive visualisation functionality as well as network analysis techniques. Originally developed as part of the Hackout3 event, it is now developed, maintained and featured as part of the R Epidemics Consortium (RECON). The package is available for download from the Comprehensive R Archive Network (CRAN) and GitHub.


title: Impact of coronavirus outbreak on NO(2) pollution assessed using TROPOMI and OMI observations

text: Spaceborne NO(2) column observations from two high‐resolution instruments, TROPOMI onboard Sentinel‐5 Precursor and OMI on Aura, reveal unprecedented NO(2) decreases over China, South Korea, Western Europe and the U.S. as a result of public health measures enforced to contain the coronavirus disease outbreak (Covid‐19) in January‐April 2020. The average NO(2) column drop over all Chinese cities amounts to ‐40% relative to the same period in 2019, and reaches up to a factor of ~2 at heavily hit cities, e.g. Wuhan, Jinan, while the decreases in Western Europe and the U.S. are also significant (‐20 to ‐38%). In contrast with this, although Iran is also strongly affected by the disease, the observations do not show evidence of lower emissions, reflecting more limited health measures.


title: Robots, pipelines, polyproteins: Enabling multiprotein expression in prokaryotic and eukaryotic cells

text: Abstract Multiprotein complexes catalyze vital biological functions in the cell. A paramount objective of the SPINE2 project was to address the structural molecular biology of these multiprotein complexes, by enlisting and developing enabling technologies for their study. An emerging key prerequisite for studying complex biological specimens is their recombinant overproduction. Novel reagents and streamlined protocols for rapidly assembling co-expression constructs for this purpose have been designed and validated. The high-throughput pipeline implemented at IGBMC Strasbourg and the ACEMBL platform at the EMBL Grenoble utilize recombinant overexpression systems for heterologous expression of proteins and their complexes. Extension of the ACEMBL platform technology to include eukaryotic hosts such as insect and mammalian cells has been achieved. Efficient production of large multicomponent protein complexes for structural studies using the baculovirus/insect cell system can be hampered by a stoichiometric imbalance of the subunits produced. A polyprotein strategy has been developed to overcome this bottleneck and has been successfully implemented in our MultiBac baculovirus expression system for producing multiprotein complexes.


title: Cardiac injuries in patients with coronavirus disease 2019: Not to be ignored

text: Abstract Objective To describe the clinical features of coronavirus disease 2019 (COVID-19). Methods We recruited 73 patients with COVID-19 [49 men and 24 women; average age: 58.36 years (SD: 14.31)] admitted to the intensive care unit of Wuhan Jinyintan Hospital from December 30, 2019 to February 16, 2020. Demographics, underlying diseases, and laboratory test results on admission were collected and analyzed. Data were compared between survivors and non-survivors. Results The non-survivors were older (65.46 [SD 9.74] vs 46.23 [12.01]) and were more likely to have chronic medical illnesses. Non-survivors tend to develop more severe lymphopenia, with higher C-reactive protein, interleukin-6, D-dimer, and hs-Troponin I(hs-TnI) levels. Patients with elevated hs-TnI levels on admission had shorter duration from symptom onset to death. Increased hs-TnI level was related to dismal prognosis. Death risk increased by 20.8% when the hs-TnI level increased by one unit. After adjusting for inflammatory or coagulation index, the independent predictive relationship between hs-TnI and death disappeared. Conclusions Cardiac injury may occur at the early stage of COVID-19, which is associated with high mortality. Inflammatory factor cascade and coagulation abnormality may be the potential mechanisms of COVID-19 combined with cardiac injury.


title: Digital Health Management During and Beyond the COVID-19 Pandemic: Opportunities, Barriers, and Recommendations

text: During the coronavirus disease (COVID-19) crisis, digital technologies have become a major route for accessing remote care. Therefore, the need to ensure that these tools are safe and effective has never been greater. We raise five calls to action to ensure the safety, availability, and long-term sustainability of these technologies: (1) due diligence: remove harmful health apps from app stores; (2) data insights: use relevant health data insights from high-quality digital tools to inform the greater response to COVID-19; (3) freely available resources: make high-quality digital health tools available without charge, where possible, and for as long as possible, especially to those who are most vulnerable; (4) digital transitioning: transform conventional offline mental health services to make them digitally available; and (5) population self-management: encourage governments and insurers to work with developers to look at how digital health management could be subsidized or funded. We believe this should be carried out at the population level, rather than at a prescription level.


title: 13 Ebola virus: where does it come from and where is it going?

text: Publisher Summary This chapter discusses the emergence and natural history of Ebola viruses. The fact that the Ebola virus subtypes, which have caused human disease episodes, have been different from one another makes it clear that a common source human-to-human transmission chain extending across sub-Saharan Africa is not the case and rather, virus subtypes lodged at or near each site of the recent human disease episodes have been responsible. Filovirus virions are enveloped and pleomorphic, appearing filamentous or bacilliform, U-shaped, 6-shaped, or circular. Particles have a uniform diameter of 80 nm, but vary greatly in length. The degree of the stability of filovirus sequences overall and the absence of genetic variability among Ebola virus isolates obtained within an outbreak match the character of other member viruses of the order, Mononegavirales. In rhesus monkeys, cynomolgus monkeys, African green monkeys, and baboons inoculated with Marburg virus or the Zaire subtype of Ebola virus, the incubation period is 4–6 days, during which time virus replicates to high titer in the reticuloendothelial system, endothelium, liver, and lungs. It is found that with the onset of clinical disease, there is severe necrosis of these target organs, which is most evident in the liver and there is an interstitial hemorrhage, which is most evident in the gastrointestinal tract.


Fibrinolysis Shutdown and Thrombosis in Severe SARS-CoV-2 (COVID-19)


Protocol for teledentistry during COVID-19 in Armed Forces dental establishments


title: Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

text: BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.


title: Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate Immunity

text: Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here we identify the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulates an association between PLZF, the promyelocytic leukemia protein and histone deacetylase 1, to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice have a specific ISG defect and as a result are more susceptible to viral infection. This susceptibility correlates with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.


title: The Impact of Middle East Respiratory Syndrome Outbreak on Trends in Emergency Department Utilization Patterns

text: Changes occurred in the patterns of utilization of emergency medical services during the Middle East respiratory syndrome (MERS) outbreak. The purpose of this study was to analyze the patterns of adult and pediatric patients who visited the emergency department (ED) during the outbreak. This retrospective study was conducted by analyzing changes in the patterns of visits among adult and pediatric patients in the ED at one tertiary teaching hospital in Korea. The study was performed from June 1, 2013 to July 31, 2015. The MERS outbreak period was from June 1 to July 31, 2015, and we compared that period to the same periods in 2013 and 2014. We compared and analyzed the patients' characteristics, emergency severity index (ESI) level at the visit, cause of visit, diagnosis, final dispositions, injury/non-injury, length of stay at the ED (EDLOS), and hospitalization rate. A total of 9,107 patients visited the ED during this period. Of these patients, 2,572 (28.2%) were pediatric patients and 6,535 (71.8%) were adult patients. The most common cause of an ED visit was fever (adult patients: 21.6%, pediatric patients: 56.2%). The proportion of non-urgent visits involving an ESI level of 4 or 5 and the EDLOS decreased significantly in pediatric and adult patients in comparison to that during the past two years. This change was significant in pediatric patients. Among adult patients, the rate of injury decreased, whereas it increased among pediatric patients. During the MERS outbreak period, pediatric ED visits due to non-urgent cases decreased significantly and there were more pronounced differences in ED utilization patterns in pediatric patients than in adult patients.


title: Systemic endothelial dysfunction: a common pathway for COVID-19, cardiovascular and metabolic diseases

text: Some of the mechanisms and conditions underlying endothelial dysfunction.A-human skin capillaries, visualized with high-resolution intravital color microscopy in the finger of a patient with obesity, metabolic syndrome and coronary artery disease.B- healthy control. The reduced number of capillaries can be noticed in A compared to B. [Figure: see text]


title: Recombinase‐Based Isothermal Amplification of Nucleic Acids with Self‐Avoiding Molecular Recognition Systems (SAMRS)

text: Recombinase polymerase amplification (RPA) is an isothermal method to amplify nucleic acid sequences without the temperature cycling that classical PCR uses. Instead of using heat to denature the DNA duplex, RPA uses recombination enzymes to swap single‐stranded primers into the duplex DNA product; these are then extended using a strand‐displacing polymerase to complete the cycle. Because RPA runs at low temperatures, it never forces the system to recreate base‐pairs following Watson–Crick rules, and therefore it produces undesired products that impede the amplification of the desired product, complicating downstream analysis. Herein, we show that most of these undesired side products can be avoided if the primers contain components of a self‐avoiding molecular recognition system (SAMRS). Given the precision that is necessary in the recombination systems for them to function biologically, it is surprising that they accept SAMRS. SAMRS‐RPA is expected to be a powerful tool within the range of amplification techniques available to scientists.


title: Identification of common and severe COVID-19: the value of CT texture analysis and correlation with clinical characteristics

text: OBJECTIVE: To explore the value of CT texture analysis (CTTA) for determining coronavirus disease 2019 (COVID-19) severity. METHODS: The clinical and CT data of 81 patients with COVID-19 were retrospectively analyzed. The texture features were extracted using LK2.1. The two-sample t test or Mann–Whitney U test was used to find the significant features. Minimum redundancy and maximum relevance (MRMR) method was performed to find the features with maximum correlation and minimum redundancy. These features were then used to construct a radiomics texture model to discriminate the severe patients using multivariate logistic regression method. Besides, a clinical model was also built. ROC analyses were conducted to evaluate the performance of two models. The correlations of clinical features and textural features were analyzed using the Spearman correlation analysis. RESULTS: Of the total cases included, 60 were common and 21 were severe. (1) For textural features, 20 radiomics features selected by MRMR showed good performance in discriminating the two groups (AUC > 70%). (2) For clinical features, chi-square tests or Mann–Whitney U tests identified 16 clinical features as significant, and 12 were discriminative (p < 0.05) between two groups analyzed by univariate logistic analysis. Of these, 10 had an AUC > 70%. (3) Prediction models for textural features and clinical features were established, and both showed high predictive accuracy. The AUC values of textural features and clinical features were 0.93 (0.86–1.00) and 0.95 (0.95–0.99), respectively. (4) The Spearman correlation analysis showed that most textural and clinical features had above-moderate correlations with disease severity (> 0.4). CONCLUSION: Texture analysis can provide reliable and objective information for differential diagnosis of COVID-19. KEY POINTS: • CT texture analysis can well differentiate common and severe COVID-19 patients. • Some textural features showed above-moderate correlations with clinical factors. • CT texture analysis can provide useful information to judge the severity of COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-07012-3) contains supplementary material, which is available to authorized users.


title: Cortex phellodendri Extract Relaxes Airway Smooth Muscle

text: Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K(+)- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K(+) was also blocked by nifedipine, a selective blocker of L-type Ca(2+) channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca(2+) channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.


title: Digital technology can revolutionize mental health services delivery: The COVID‐19 crisis as a catalyst for change

text: The unprecedented COVID‐19 crisis presents an imperative for mental health care systems to make digital mental health interventions a routine part of care. Already because of COVID‐19, many therapists have rapidly moved to using telehealth in place of in‐person contact. In response to this shift, Waller and colleagues compiled a series of expert recommendations to help clinicians pivot to delivering teletherapy to address eating disorders during COVID‐19. However, numerous barriers still impede widespread adoption and implementation of digital interventions. In this commentary, we aim to extend the recommendations for clinicians offered by Waller and colleagues by presenting a roadmap of the systems‐ and policy‐level requirements that are needed. We advocate for addressing barriers associated with training, licensing, safety, privacy, payment, and evaluation, as these factors have greatly limited use of these promising interventions. We also indicate that longer‐term goals should include introducing truly innovative digital mental health practices, such as stepped‐care models and simultaneously providing preventive and self‐management services in addition to clinical services, into the health care system. Now is the time to catalyze change and comprehensively address the barriers that have prevented widespread delivery of these efficacious digital services to the millions of people who would benefit.


title: SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

text: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2, as well as the viral S protein priming protease TMPRSS2 thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2, as well as the protease TMPRSS2, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.