title: The impact of cold on the respiratory tract and its consequences to respiratory health

text: The increasing use, and sometimes the abuse, particularly in industrialized countries of air conditioning at home, in car, hotel and shopping centres has highlighted new emerging public health issues, resulting from exposure of the airways to cool air or, more properly, resulting from sudden temperature changes. This is part of a wider problem, relating to air quality in indoor environment, such as homes or offices, where people spend more than 90% of their time. In particular, if indoor exposure occurs quickly and without any gradual adaptation to a temperature 2°–3° lower than the external temperature and especially with a 5° difference (avoiding indoor temperature below 24°) and an humidity between 40 and 60%, there is a risk of negative consequences on the respiratory tract and the patient risks to be in a clinical condition characterized by an exacerbation of the respiratory symptoms of his chronic respiratory disease (asthma and COPD) within a few hours or days. Surprisingly, these effects of cold climate remain out of the focus of the media unless spells of unusually cold weather sweep through a local area or unstable weather conditions associated with extremely cold periods of increasing frequency and duration. Moreover, the energy consumed by air conditioning induces an increase of CO(2) in atmosphere with increase of global warming. There is a need to better define the consequences of repeated exposure to cold air and the mechanisms by which such exposure could modify airway function and affect the outcomes of patients with pre-existing airway disease. This could help to promote adequate policy and public health actions to face the incoming challenges induced by climate change and global warming.


title: Isolation and Propagation of Coronaviruses in Embryonated Eggs

text: The embryonated egg is a complex structure comprised of an embryo and its supporting membranes (chorioallantoic, amniotic, yolk). The developing embryo and its membranes provide the diversity of cell types that are needed for successful replication of a wide variety of different viruses. Within the family Coronaviridae the embryonated egg has been used as a host system primarily for two avian coronaviruses within the genus Gammacoronavirus, infectious bronchitis virus (IBV) and turkey coronavirus (TCoV). The embryonated egg also has been shown to be suitable for isolation and propagation of pheasant coronavirus, a proposed member of the Gammacoronavirus genus. IBV and pheasant coronavirus replicate well in the embryonated chicken egg, regardless of inoculation route; however, the allantoic route is favored as these viruses replicate well in epithelium lining the chorioallantoic membrane, with high virus titers found in these membranes and associated allantoic fluids. TCoV replicates only in epithelium lining the embryo intestines and bursa of Fabricius, thus amniotic inoculation is required for isolation and propagation of this virus. Embryonated eggs also provide a potential host system for detection and characterization of other, novel coronaviruses.


title: Fact-finding Survey of Nosocomial Infection Control in Hospitals in Kathmandu, Nepal—A Basis for Improvement

text: The purpose of this study was to investigate the actual conditions of nosocomial infection control in Kathmandu City, Nepal as a basis for the possible contribution to its improvement. The survey was conducted at 17 hospitals and the methods included a questionnaire, site visits and interviews. Nine hospitals had manuals on nosocomial infection control, and seven had an infection control committee (ICC). The number of hospitals that met the required amount of personal protective equipment preparation was as follows: gowns (13), gloves (13), surgical masks (12). Six hospitals had carried out in-service training over the past one year, but seven hospitals responded that no staff had been trained. Eight hospitals were conducting surveillance based on the results of bacteriological testing. The major problems included inadequate management of ICC, insufficient training opportunities for hospital staff, and lack of essential equipment. Moreover, increasing bacterial resistance to antibiotics was recognized as a growing issue. In comparison with the results conducted in 2003 targeting five governmental hospitals, a steady improvement was observed, but further improvements are needed in terms of the provision of high quality medical care. Particularly, dissemination of appropriate manuals, enhancement of basic techniques, and strengthening of the infection control system should be given priority.


title: Is there an ideal animal model for SARS?

text: The outbreak of severe acute respiratory syndrome (SARS) in 2003 was controlled by public health measures at a time when specific interventions such as antiviral drugs, vaccines and immunotherapy were not available. Since then, several animal models have been developed for the study of SARS and, although no model replicates the human disease in all aspects, the use of animal models for SARS has led to the establishment of several important principles for vaccine and immunotherapy. Consistency and reproducibility of findings in a given model must be demonstrated to establish the superiority of one model over others. Here, we suggest aspects of an ideal animal model for studies of SARS pathogenesis and vaccine development and present our assessment of the strengths and limitations of the current animal models for SARS.


title: Early Transmission Dynamics of Novel Coronavirus (COVID-19) in Nigeria

text: On 31 December 2019, the World Health Organization (WHO) was notified of a novel coronavirus disease in China that was later named COVID-19. On 11 March 2020, the outbreak of COVID-19 was declared a pandemic. The first instance of the virus in Nigeria was documented on 27 February 2020. This study provides a preliminary epidemiological analysis of the first 45 days of COVID-19 outbreak in Nigeria. We estimated the early transmissibility via time-varying reproduction number based on the Bayesian method that incorporates uncertainty in the distribution of serial interval (time interval between symptoms onset in an infected individual and the infector), and adjusted for disease importation. By 11 April 2020, 318 confirmed cases and 10 deaths from COVID-19 have occurred in Nigeria. At day 45, the exponential growth rate was 0.07 (95% confidence interval (CI): 0.05–0.10) with a doubling time of 9.84 days (95% CI: 7.28–15.18). Separately for imported cases (travel-related) and local cases, the doubling time was 12.88 days and 2.86 days, respectively. Furthermore, we estimated the reproduction number for each day of the outbreak using a three-weekly window while adjusting for imported cases. The estimated reproduction number was 4.98 (95% CrI: 2.65–8.41) at day 22 (19 March 2020), peaking at 5.61 (95% credible interval (CrI): 3.83–7.88) at day 25 (22 March 2020). The median reproduction number over the study period was 2.71 and the latest value on 11 April 2020, was 1.42 (95% CrI: 1.26–1.58). These 45-day estimates suggested that cases of COVID-19 in Nigeria have been remarkably lower than expected and the preparedness to detect needs to be shifted to stop local transmission.


title: Clustered Cases of Pneumonia among Healthcare Workers over a 1-year Period in Three Italian Hospitals: Applying the WHO SARS Alert

text: BACKGROUND: The World Health Organization (WHO) has recommended that a severe acute respiratory syndrome (SARS) alert should be raised when two or more healthcare workers (HCW) in the same health care unit fulfil the SARS clinical criteria, with onset of illness in the same 10-day period. However, in a number of European countries (including Italy) data on reasons for sickness absence are not routinely collected within current HCW worker sickness reporting systems, because of concerns about privacy. To help plan for the implementation of the proposed alert system in Italy, we aimed to determine the minimum number of alert cases defining a cluster. PATIENTS AND METHODS: Sickness absences longer than 7 days in HCW employed in three hospitals in 2003, were identified by checking the hospitals’ administrative databases. HCW with onset of illness in the same 10-day period were contacted and asked whether they have been diagnosed with pneumonia. RESULTS: Overall, 273 absences > 7 days were recorded and 36 clusters of at least two absences > 7 days were identified; a total of 94 HCW were involved in these clusters. Only two HCW involved in different clusters, reported pneumonia. CONCLUSION: The occurrence of clusters of two or more cases of pneumonia in HCW in the same hospital unit appears to be an uncommon event, and thus the alert system proposed is not likely to result in large numbers of false positive alerts. However, it may be difficult to implement this alert system in countries where clinical data on sickness absences are not routinely collected, and alternative mechanisms should be considered.


title: Grouper interferon-induced transmembrane protein 3 (IFITM3) inhibits the infectivity of iridovirus and nodavirus by restricting viral entry

text: Interferon-induced transmembrane proteins (IFITMs) have been identified as important host restriction factors in mammals for the control of infection by multiple viruses. However, the antiviral functions of IFITMs against fish viruses remain largely uncertain. In this study, the IFITM3 homolog from orange spotted grouper (EcIFITM3) was cloned and its roles in grouper virus infection were investigated. The full-length cDNA of EcIFITM3 was 737 bp, which was composed of a 16 bp 5′-UTR, a 274 bp 3′-UTR, and a 447 bp ORF. EcIFITM3 encodes a 148-amino-acid polypeptide, which contains five domains, i.e., the N-terminal domain (aa 1–65), TM1 (aa 66–90), the cytoplasmic domain (aa 91–110), TM2 (aa 111–140), and the C-terminal domain (aa 141–148), and shares 78% and 47% identity with IFITM3 of gilthead seabream (Sparus aurata) and human (Homo sapiens), respectively. EcIFITM3 mRNA was detected in 12 tissues of healthy groupers, with the highest expression levels in the head kidney. Additionally, the in vitro mRNA levels of EcIFITM3 were significantly upregulated by infection with Singapore grouper iridovirus (SGIV) or red spotted grouper nervous necrosis virus (RGNNV), or treatment with polyinosinic-polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Subcellular localization analysis showed that EcIFITM3 was mainly distributed in the cell membrane of grouper cells. In vitro, the ectopic expression of EcIFITM3 inhibited SGIV and RGNNV infection, as demonstrated by the reduced severity of the cytopathic effect, decreased virus production, and low levels of viral mRNA and proteins. Consistently, knockdown of EcIFITM3 by small interfering RNAs (siRNAs) enhanced SGIV and RGNNV replication. EcIFITM3 overexpression and knockdown experiments both suggested that EcIFITM3 inhibits the infection of SGIV and RGNNV by restricting virus entry.


title: Ingestion of Exopolymers from Aureobasidium pullulans Reduces the Duration of Cold and Flu Symptoms: A Randomized, Placebo-Controlled Intervention Study

text: AIM: The objective of the study was to assess the efficacy of exopolymers from Aureobasidium pullulans (EAP) on the incidence of colds and flu in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 76 subjects (30–70 years of age) were recruited from the general population. The subjects were instructed to take one capsule per day of either EAP or a placebo for a period of 8 weeks. The duration of cold and flu symptoms, a primary variable in assessing effectiveness, and serum cytokine levels as well as WBC counts as secondary variables were also evaluated. RESULTS: EAP was associated with a statistically significant decrease in the duration of cold and flu symptoms, a primary variable in assessing effectiveness. Although cold and flu symptom levels were not significantly different at a significance level of 5%, the cold and flu symptom levels of the EAP group were less severe compared to the placebo group. No statistically significant changes of serum cytokine levels as well as WBC counts were observed. CONCLUSION: The results showed that EAP is a useful pharmaceutical and functional food material for preventing and treating colds and flu.


title: Estimation and tests for power-transformed and threshold GARCH models

text: Abstract Consider a class of power-transformed and threshold GARCH ( p , q ) (PTTGRACH ( p , q ) ) model, which is a natural generalization of power-transformed and threshold GARCH(1,1) model in Hwang and Basawa [2004. Stationarity and moment structure for Box–Cox transformed threshold GARCH(1,1) processes. Statistics & Probability Letters 68, 209–220.] and includes the standard GARCH model and many other models as special cases. We first establish the asymptotic normality for quasi-maximum likelihood estimators (QMLE) of the parameters under the condition that the error distribution has finite fourth moment. For the case of heavy-tailed errors, we propose a least absolute deviations estimation (LADE) for PTTGARCH ( p , q ) model, and prove that the LADE is asymptotically normally distributed under very weak moment conditions. This paves the way for a statistical inference based on asymptotic normality for heavy-tailed PTTGARCH ( p , q ) models. As a consequence, we can construct the Wald test for GARCH structure and discuss the order selection problem in heavy-tailed cases. Numerical results show that LADE is more accurate than QMLE for heavy-tailed errors. Furthermore, the theory is applied to the daily returns of the Hong Kong Hang Seng Index, which suggests that asymmetry and nonlinearity could be present in the financial time series and the PTTGARCH model is capable of capturing these characteristics. As for the probabilistic structure of PTTGARCH ( p , q ) model, we give in the appendix a necessary and sufficient condition for the existence of a strictly stationary solution of the model, the existence of the moments and the tail behavior of the strictly stationary solution.


title: The RNA capping machinery as an anti‐infective target

text: A number of different human pathogens code for their own enzymes involved in the synthesis of the RNA cap structure. Although the RNA cap structures originating from human and microbial enzymes are often identical, the subunit composition, structure and catalytic mechanisms of the microbial‐encoded enzymes involved in the synthesis of the RNA cap structure are often significantly different from those of host cells. As a consequence, these pathogenic cap‐forming enzymes are potential targets for antimicrobial drugs. During the past few years, experimental studies have started to demonstrate that inhibition of the RNA capping activity is a reasonable approach for the development of antimicrobial agents. The combination of structural, biochemical, and molecular modeling studies are starting to reveal novel molecules that can serve as starting blocks for the design of more potent and specific antimicrobial agents. Here, we examine various strategies that have been developed to inhibit microbial enzymes involved in the synthesis of the RNA cap structure, emphasizing the challenges remaining to design potent and selective drugs. WIREs RNA 2011 2 184–192 DOI: 10.1002/wrna.43 1.. RNA Processing > Capping and 5' End Modifications.


title: Harnessing resolving‐based therapeutics to treat pulmonary viral infections: What can the future offer to COVID‐19?

text: Inflammation is generally believed to be a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Multiple mediators that drive the resolution of inflammation have been described. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro‐resolving molecules or strategies that promote their increase tend to decrease inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti‐inflammatory, pro‐resolving, anti‐thrombogenic and anti‐microbial effects of pro‐resolution mediators may be useful in the treatment of the late stages of disease in patients with COVID‐19.


title: Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom

text: • Venous thrombosis is common in patients with severe COVID-19 pneumonia. • Many of these thromboses may be immunothromboses due to local inflammation, rather than thromboembolic disease. • Anticoagulated patients with COVID-19 pneumonia have a risk of major bleeding.


title: Differential Regulation of Self-reactive CD4(+) T Cells in Cervical Lymph Nodes and Central Nervous System during Viral Encephalomyelitis

text: Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells. In this model, immune-mediated demyelination is associated with induction of SR T cells after viral control. However, their decline during persisting infection, despite ongoing demyelination, suggests an active control mechanism. Antigen-specific IL-10-secreting CD4(+) T cells (Tr1) and Foxp3(+) regulatory T cells (Tregs), both known to control autoimmunity and induced following JHMV infection, were assessed for their relative in vivo suppressive function of SR T cells. Ablation of Foxp3(+) Tregs in chronically infected DEREG mice significantly increased SR CD4(+) T cells within cervical lymph nodes (CLN), albeit without affecting their numbers or activation within the CNS compared to controls. In contrast, infected IL-27 receptor deficient (IL-27R(−/−)) mice, characterized by a drastic reduction of Tr1 cells, revealed that SR CD4(+) T cells in CLN remained unchanged but were specifically increased within the CNS. These results suggest that distinct Treg subsets limit SR T cells in the draining lymph nodes and CNS to maximize suppression of SR T-cell-mediated autoimmune pathology. The JHMV model is thus valuable to decipher tissue-specific mechanisms preventing autoimmunity.


title: Social Factors Associated with AIDS and SARS

text: We conducted a survey of 928 New York City area residents to assess knowledge and worry about AIDS and SARS. Specific sociodemographic groups of persons were more likely to be less informed and more worried about contracting the diseases.


A review of medical masks and respirators for use during an influenza pandemic


Calendrier vaccinal des nourrissons et COVID-19


title: HIV-1 Modulates the tRNA Pool to Improve Translation Efficiency

text: Despite its poorly adapted codon usage, HIV-1 replicates and is expressed extremely well in human host cells. HIV-1 has recently been shown to package non-lysyl transfer RNAs (tRNAs) in addition to the tRNA(Lys) needed for priming reverse transcription and integration of the HIV-1 genome. By comparing the codon usage of HIV-1 genes with that of its human host, we found that tRNAs decoding codons that are highly used by HIV-1 but avoided by its host are overrepresented in HIV-1 virions. In particular, tRNAs decoding A-ending codons, required for the expression of HIV's A-rich genome, are highly enriched. Because the affinity of Gag-Pol for all tRNAs is nonspecific, HIV packaging is most likely passive and reflects the tRNA pool at the time of viral particle formation. Codon usage of HIV-1 early genes is similar to that of highly expressed host genes, but codon usage of HIV-1 late genes was better adapted to the selectively enriched tRNA pool, suggesting that alterations in the tRNA pool are induced late in viral infection. If HIV-1 genes are adapting to an altered tRNA pool, codon adaptation of HIV-1 may be better than previously thought.


Medical care of atrophic gastritis patients during COVID-19 pandemic: results of telemedicine in a referral center


title: Large-scale production and purification of VLP-based vaccines

text: Abstract Virus-like particles (VLPs) hold tremendous potential as vaccine candidates. These innovative biopharmaceuticals present the remarkable advantages of closely mimicking the three-dimensional nature of an actual virus while lacking the virus genome packaged inside its capsid. As a result, an equally efficient but safer prophylaxis is anticipated as compared to inactivated or live attenuated viral vaccines. With the advent of successful cases of approved VLP-based vaccines, pharmaceutical companies are indeed redirecting their resources to the development of such products. This paper reviews the current choices and trends of large-scale production and purification of VLP-based vaccines generated through the baculovirus expression vector system using insect cells.


title: Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity

text: The interferon‐induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV‐1 virions and inhibit virus fusion and cell‐to‐cell spread, with IFITM3 showing the greatest potency. Here, we report that amino‐terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV‐1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino‐terminal mutations that modify protein localization and function. This suggests that “runaway” IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade‐off in antiviral specificity, as variants exhibiting enhanced activity against HIV‐1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.


title: Severe human parechovirus sepsis beyond the neonatal period

text: Abstract Here we describe a case of viral sepsis beyond the neonatal period caused by human parechovirus subtype 3 (HPeV-3), which manifested as cardio-respiratory failure, hepatitis, and necrotizing enterocolitis (NEC). HPeV-1 and 2 were originally classified as enteroviruses but the advent of sequence analysis led to them being recognized as a new genus in the picornavirus family. Subsequently, nine additional HPeV strains have been reported including HPeV-3 in 1999. 1 The spectrum of disease that these viruses may cause is still unknown, and they are rarely screened for in clinical practice.


title: Atypical pneumonia—time to breathe new life into a useful term?

text: Summary The term atypical pneumonia was originally used to describe an unusual presentation of pneumonia. It is now more widely used in reference to either pneumonia caused by a relatively common group of pathogens, or to a distinct clinical syndrome the existence of which is difficult to demonstrate. As such, the use of atypical pneumonia is often inaccurate, potentially confusing, and of dubious scientific merit. We need to return to the original meaning of atypical pneumonia and restrict its use to describe pneumonia that is truly unusual in clinical presentation, epidemiology, or both.


title: Chapter 8 Business Strategies and Risk Factors

text: The offshore pipeline construction service industry has seen varying degrees of consolidation and integration over the years. The demand for pipeline construction fluctuates from year to year and by geographic region. During periods of sustained low oil prices demand for services are reduced, causing contractors to resize operations to maintain a competitive position, to form alliances and partnerships in search of opportunities, and to stack and dismantle less competitive vessels to reduce cost. The purpose of this chapter is to describe the business models and strategies employed by offshore construction companies and their impact on operations. Operational and financial risk factors are highlighted, and the chapter concludes with company portraits.


title: Chloroquine, Hydroxychloroquine and Hearing Loss: A Study in Systemic Lupus Erythematosus Patients

text: OBJECTIVES/HYPOTHESIS: Antimalarial drugs (chloroquine and hydroxychloroquine) are widely used for the treatment of systemic lupus erythematosus (SLE). However, these drugs may have side effects such as hearing loss. This study aimed to describe the hearing function in SLE patients using antimalarials. Secondarily, this study aimed to investigate whether SLE causes hearing loss and if there are any serological or clinical aspects of this diseases associated with inner ear damage. STUDY DESIGN: Cross‐sectional study. METHODS: This study included 84 individuals (43 SLE patients and 41 controls) with audiometry and tympanometry tests. Epidemiological, clinical, serological, and treatment profiles of SLE patients were extracted from the charts. RESULTS: SLE patients had more sensorineural hearing loss than controls (23.2% vs. 0; P = .001). Pure‐tone averages in SLE patients using antimalarials and not using antimalarials were similar (8.75 vs. 8.75; P = .63). At 8,000 Hz, antimalarial dug nonusers performed worse than users (10.00 vs. 22.50; P = .03). Tympanometry was normal in all participants. SLE serological and clinical profiles in patients with and without hearing loss were the same (all P = nonsignificant). CONCLUSIONS: There is a high prevalence of hearing loss in SLE that is not affected by antimalarial drug use. LEVEL OF EVIDENCE: 3b Laryngoscope, 2020


title: Modeling particle dispersion and deposition in indoor environments

text: Abstract Particle dispersion and deposition in man-made enclosed environments are closely related to the well-being of occupants. The present study developed a three-dimensional drift-flux model for particle movements in turbulent indoor airflows, and combined it into Eulerian approaches. To account for the process of particle deposition at solid boundaries, a semi-empirical deposition model was adopted in which the size-dependent deposition characteristics were well resolved. After validation against the experimental data in a scaled isothermal chamber and in a full-scale non-isothermal environmental chamber, the drift-flux model was used to investigate the deposition rates and human exposures to particles from two different sources with three typical ventilation systems: mixing ventilation (MV), displacement ventilation (DV), and under-floor air distribution (UFAD). For particles originating from the supply air, a V-shaped curve of the deposition velocity variation as a function of particle size was observed. The minimum deposition appeared at 0.1– 0.5 μ m . For supermicron particles, the ventilation type and air exchange rate had an ignorable effect on the deposition rate. The movements of submicron particles were like tracer gases while the gravitational settling effect should be taken into account for particles larger than 2.5 μ m . The temporal increment of human exposure to a step-up particle release in the supply air was determined, among many factors, by the distance between the occupant and air outlet. The larger the particle size, the lower the human exposure. For particles released from an internal heat source, the concentration stratification of small particles (diameter < 10 μ m ) in the vertical direction appeared with DV and UFAD, and it was found the advantageous principle for gaseous pollutants that a relatively less-polluted occupied zone existed in DV and UFAD was also applicable to small particles.


title: Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome

text: The medical records of 62 cats with clinical signs of central nervous system disease and accompanying inflammatory cerebrospinal fluid (CSF) analysis were examined retrospectively to determine if signalment, clinical signs, CSF analysis and ancillary testing could accurately predict the type of central nervous system disease that was present. An inflammatory CSF was defined as one in which a total nucleated cell count was greater than 5cells/μl or one in which the total nucleated cell count was normal but the nucleated cell differential count was abnormal. Sex, degree of CSF inflammation, neuroanatomical location and systemic signs provided little contributory information to the final diagnosis. In 63% of the cases a presumptive diagnosis could be made based on a combination of clinical signs, clinicopathological data and ancillary diagnostic tests. CSF analysis alone was useful only in the diagnosis of cats with feline infectious peritonitis, Cryptococcus species infection, lymphoma and trauma. Overall, despite extensive diagnostic evaluation, a specific diagnosis could not be made in 37% of cats. The prognosis for cats with inflammatory CSF was poor with 77% of cats surviving less than 1 year.


title: Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong

text: Summary Objective Human infections caused by avian influenza virus A(H7N9) re-emerged in late 2013. We reported the first Hong Kong patient without risk factors for severe A(H7N9) disease. Methods Direct sequencing was performed on the endotracheal aspirate collected from a 36-year-old female with history of poultry contact. Bioinformatic analysis was performed to compare the current strain and previous A(H7N9) isolates. Results The influenza A/Hong Kong/470129/2013 virus strain was detected in a patient with acute respiratory distress syndrome, deranged liver function and coagulation profile, cytopenia, and rhabdomyolysis. The HA, NA and MP genes of A/Hong Kong/470129/2013 cluster with those of other human A(H7N9) strains. The PB1, PB2 and NS genes are most closely related to those of A/Guangdong/1/2013 strain identified in August 2013, but are distinct from those of other human and avian A(H7N9) strains. The other internal genes NP and PA genes are more closely related to those of non-A(H7N9) avian influenza A viruses. A unique PA L336M mutation, associated with increased polymerase activity, was found. The patient required salvage by extracorporeal membrane oxygenation. Conclusions The A/Hong Kong/470129/2013 virus is a novel reassortant derived from A/Guangdong/1/2013 virus. The unique mutation PA L336M may enhance viral replication and therefore disease severity.


title: Practical Considerations for Solid Organ Transplantation During the COVID-19 Global Outbreak: The Experience from Singapore

text: The current coronavirus disease 2019 (COVID-19) pandemic has not only caused global social disruptions but has also put tremendous strain on healthcare systems worldwide. With all attention and significant effort diverted to containing and managing the COVID-19 outbreak (and understandably so), essential medical services such as transplant services are likely to be affected. Closure of transplant programs in an outbreak caused by a highly transmissible novel pathogen may be inevitable owing to patient safety. Yet program closure is not without harm; patients on the transplant waitlist may die before the program reopens. By adopting a tiered approach based on outbreak disease alert levels, and having hospital guidelines based on the best available evidence, life-saving transplants can still be safely performed. We performed a lung transplant and a liver transplant successfully during the COVID-19 era. We present our guidelines and experience on managing the transplant service as well as the selection and management of donors and recipients. We also discuss clinical dilemmas in the management COVID-19 in the posttransplant recipient.


title: Troubling care in the neonatal intensive care unit

text: The neonatal intensive care unit (NICU) is a site of medical treatment for premature and critically ill infants. It is a space populated by medical teams and their patients, as well as parents and family. Each actor in this space negotiates providing and practicing care. In this paper, we step away from thinking about the NICU as only a space of medical care, instead, taking an anti-essentialist view, re-read care as multiple, while also troubling the community of care that undergirds it. Through an examination of the practice of kangaroo care (skin-to-skin holding), human milk production and feeding, as well as, practices related to contact/touch, we offer a portrait of the performance of the community of care in the space of the NICU. We argue that caring practices taking place in the NICU are multiple and co-produced, while simultaneously being subject to power and knowledge differentials between actors. Here we analyze the negotiations over the knowledge and practice of care(s) to open up the NICU as a particular community of care, and consider care as a both a joint accomplishment and a gatekeeping practice.


How medical education can help in a COVID‐19 crisis


title: A prospective prediction tool for understanding Crimean–Congo haemorrhagic fever dynamics in Turkey

text: Abstract Objectives We aimed to develop a prospective prediction tool on Crimean–Congo haemorrhagic fever (CCHF) to identify geographic regions at risk. The tool could support public health decision-makers in implementation of an effective control strategy in a timely manner. Methods We used monthly surveillance data between 2004 and 2015 to predict case counts between 2016 and 2017 prospectively. The Turkish nationwide surveillance data set collected by the Ministry of Health contained 10 411 confirmed CCHF cases. We collected potential explanatory covariates about climate, land use, and animal and human populations at risk to capture spatiotemporal transmission dynamics. We developed a structured Gaussian process algorithm and prospectively tested this tool predicting the future year's cases given past years' cases. Results We predicted the annual cases in 2016 and 2017 as 438 and 341, whereas the observed cases were 432 and 343, respectively. Pearson's correlation coefficient and normalized root mean squared error values for 2016 and 2017 predictions were (0.83; 0.58) and (0.87; 0.52), respectively. The most important covariates were found to be the number of settlements with fewer than 25 000 inhabitants, latitude, longitude and potential evapotranspiration (evaporation and transpiration). Conclusions Main driving factors of CCHF dynamics were human population at risk in rural areas, geographical dependency and climate effect on ticks. Our model was able to prospectively predict the numbers of CCHF cases. Our proof-of-concept study also provided insight for understanding possible mechanisms of infectious diseases and found important directions for practice and policy to combat against emerging infectious diseases.


title: The Environment and Well-Being in Urban China

text: Abstract We examine the relationship between atmospheric pollution, measured as sulphur dioxide emissions, environmental disasters, traffic congestion, access to parkland and well-being in urban China, using a large survey administered across 30 cities in 2003. We find that in cities with high levels of atmospheric pollution, environmental disasters and traffic congestion Chinese citizens report significantly lower levels of well-being ceteris paribus while in cities with greater access to parkland Chinese citizens report significantly higher levels of well-being ceteris paribus.


title: RNA structure interactions and ribonucleoprotein processes of the influenza A virus

text: In one more years, we will ‘celebrate’ an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins and the protein products generated from alternative splicing, and on the role of base pairing in RNA structure. We highlight the main events associated with viral entry into the cell, the transcription and replication process, an export of the viral genetic material from the nucleus and the final release of the virus. We discuss the observed potential roles of RNA secondary structure (the RNA base-pairing arrangement) and RNA/RNA interactions in this scheme.


title: Chapter 504 Sindbis Virus nsP2 Endopeptidase

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 494 is Sindbis Virus nsP2 Endopeptidase. Keywords: Sindbis virus, nsP2 endopeptidase, alphaviruses.


title: Successful Outcome of Human Metapneumovirus (hMPV) Pneumonia in a Lung Transplant Recipient Treated With Intravenous Ribavirin

text: Human metapneumovirus (hMPV) has recently been shown to be a prominent cause of respiratory infections in immunocompromised hosts, and is associated with high morbidity and mortality. We report a case of hMPV pneumonia in a lung transplant recipient presenting with respiratory failure and sepsis syndrome. hMPV was diagnosed by polymerase chain reaction, and treated with intravenous ribavirin with a successful outcome.


title: Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype

text: Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of pro-inflammatory cytokine signaling, TLR signaling, and inflammatory gene expression. Furthermore, mice genetically lacking SHP-1 (me/me) display a profound susceptibility to inflammatory CNS demyelination relative to wild type mice. In particular, SHP-1 deficiency may act predominantly in inflammatory macrophages to increase CNS demyelination as SHP-1-deficient macrophages display co-expression of inflammatory effector molecules and increased demyelinating activity in me/me mice. Recently, we reported that PBMCs of multiple sclerosis (MS) patients have a deficiency in SHP-1 expression relative to normal control subjects indicating that SHP-1 deficiency may play a similar role in MS as to that seen in mice. Therefore, it became essential to examine the specific expression and function of SHP-1 in macrophages from MS patients. Herein, we document that macrophages of MS patients have deficient SHP-1 protein and mRNA expression relative to those of normal control subjects. To examine functional consequences of the lower SHP-1, the activation of STAT6, STAT1, and NF-κB was quantified and macrophages of MS patients showed increased activation of these transcription factors. In accordance with this observation, several STAT6-, STAT1-, and NF-κB-responsive genes that mediate inflammatory demyelination were increased in macrophages of MS patients following cytokine and TLR agonist stimulation. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. In conclusion, macrophages of MS patients display a deficiency of SHP-1 expression, heightened activation of STAT6, STAT1, and NF-κB and a corresponding inflammatory profile that may be important in controlling macrophage-mediated demyelination in MS.


title: SARS: prognosis, outcome and sequelae

text: Severe acute respiratory syndrome (SARS) is associated with considerable morbidity and mortality in the acute phase. Worldwide case fatality rate is 11% (range 7 to 27%) for the most severely affected regions. Several adverse prognostic factors have been identified, including advanced age, presence of comorbidity, higher lactose dehydrogenase levels and initial neutrophil count, but the impact of viral and other host factors on outcome is unknown. Published data on sequelae of SARS are limited. Clinical follow‐up of patients who recovered from SARS has demonstrated radiological, functional and psychological abnormalities of varying degrees. In the early rehabilitation phase, many complained of limitations in physical function from general weakness and/or shortness of breath. In a small series of subjects who underwent CT scan of the chest, over half showed some patchy changes consistent with pulmonary fibrosis. Lung function testing at 6–8 weeks after hospital discharge showed mild or moderate restrictive pattern consistent with muscle weakness in 6–20% of subjects. Mild decrease in carbon monoxide diffusing capacity was detected in a minority of subjects. Preliminary evidence suggests that these lung function abnormalities will improve over time. Psychobehavioural problems of anxiety and/or depression were not uncommon in the early recovery phase, and improved over time in the majority of patients. Avascular necrosis of the hip has been reported as another complication. The long‐term sequelae of SARS are still largely unknown. It is important to follow up these patients to detect and appropriately manage any persistent or emerging long‐term sequelae in the physical, psychological and social domains.


title: Liver Disease Associated with Non-Hepatitis Viruses

text: Abstract Hepatitis is commonly associated with certain viruses labeled as “Hepatitis” viruses. However, many other viral infections can also affect the liver ranging from mild asymptomatic elevations of aminotransferases to fulminant hepatic failure. This article will provide a brief overview on a variety of different viral infections that may be associated with significant liver pathology at least under certain conditions, for example, immunosuppression. This overview discusses key virological features, clinical presentation of associated liver disease and provides some information on diagnosis and an outline of treatment options. Thus, the overview can provide first orientation when infectious hepatitis is encountered in a patient that cannot be explained by the usual hepatitis viruses.


title: Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder

text: The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (>50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed “micturition cage,” leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition.


title: Collection efficiencies of aerosol samplers for virus-containing aerosols

text: Abstract Collection efficiencies of four bioaerosol samplers (Andersen impactor, AGI-30 impinger, gelatin filter, and nuclepore filter) were evaluated for virus-containing aerosols. Four different bacteriophages were used as surrogates for the mammalian viruses. Results showed that the collection efficiency was significantly affected by the morphology of the virus particles. For hydrophilic viruses, the collection efficiencies of the Andersen impactor, impinger, and gelatin filter were 10 times higher than that of the nuclepore filter. For hydrophilic viruses, the collection efficiencies of all four samplers were 10–100 times higher than hydrophobic viruses. The infectivity of the virus in collected samples was also evaluated for an AGI-30 impinger. Results showed that the viruses retained more infectivity when the samples were refrigerated (up to 1 day) during storage than when stored at room temperature (up to 8h). Therefore, even when refrigerated, airborne virus samples collected using an impinger should be processed as soon as possible to avoid loss of virus infectivity.


title: Improving the collection efficiency of the liquid impinger for ultrafine particles and viral aerosols by applying granular bed filtration

text: Abstract Liquid impingers are utilized to collect bioaerosols for many advantages, such as avoiding dehydration of biological agents. However, many previous studies have reported that the liquid impingers are surprisingly inefficient for the collection of ultrafine bioaerosols, with collection efficiencies <30%. In the present work, we have successfully improved the collection efficiency of the liquid impinger (AGI30) to as high as 99% for particles in the size range of 20–400nm with the aid of packed glass beads. We also systematically investigated the effects of influential factors on the collection efficiency. These factors include the volume of the sampling liquid (0, 20 and 30mL), depth (0, 7 and 10cm) of packed glass beads and sampling flow rate (4, 6 and 8 liter per min, lpm). According to our experimental results, increasing the depth of packed glass beads and the volume of sampling liquid can enhance the collection efficiency. Also, decreasing the sampling flow rate can increase the collection efficiency and reduce the loss of sampling liquid. For the sampling of viable MS2 phages, the collection efficiency of AGI30 sampler with packed glass beads is much higher than that without packed glass beads. Conclusively, this study validates that the granular bed filtration can enhance the collection efficiency of liquid impingers for submicron and ultrafine particles and viral aerosols.


title: Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry

text: Technology for comprehensive identification of biothreats in environmental and clinical specimens is needed to protect citizens in the case of a biological attack. This is a challenge because there are dozens of bacterial and viral species that might be used in a biological attack and many have closely related near-neighbor organisms that are harmless. The biothreat agent, along with its near neighbors, can be thought of as a biothreat cluster or a biocluster for short. The ability to comprehensively detect the important biothreat clusters with resolution sufficient to distinguish the near neighbors with an extremely low false positive rate is required. A technological solution to this problem can be achieved by coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS). The biothreat assay described here detects ten bacterial and four viral biothreat clusters on the NIAID priority pathogen and HHS/USDA select agent lists. Detection of each of the biothreat clusters was validated by analysis of a broad collection of biothreat organisms and near neighbors prepared by spiking biothreat nucleic acids into nucleic acids extracted from filtered environmental air. Analytical experiments were carried out to determine breadth of coverage, limits of detection, linearity, sensitivity, and specificity. Further, the assay breadth was demonstrated by testing a diverse collection of organisms from each biothreat cluster. The biothreat assay as configured was able to detect all the target organism clusters and did not misidentify any of the near-neighbor organisms as threats. Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry.


title: Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients

text: ChiCTR, ChiCTR2000029758. Registered 12 February 2020 - Retrospectively registered


title: Differential COVID-19 case positivity in New York City neighborhoods: socioeconomic factors and mobility

text: New York City has been one of the hotspots of the COVID-19 pandemic and during the first two months of the outbreak considerable variability in case positivity was observed across the city's ZIP codes. In this study, we examined: a) the extent to which the variability in ZIP code level cases can be explained by aggregate markers of socioeconomic status and daily change in mobility; and b) the extent to which daily change in mobility independently predicts case positivity. Our analysis indicates that the markers considered together explained 56% of the variability in case positivity through April 1 and their explanatory power decreased to 18% by April 30. Our analysis also indicates that changes in mobility during this time period are not likely to be acting as a mediator of the relationship between ZIP-level SES and case positivity. During the middle of April, increases in mobility were independently associated with decreased case positivity. Together, these findings present evidence that heterogeneity in COVID-19 case positivity in New York City is largely driven by neighborhood socioeconomic status.


title: Initiating respiratory hygiene and cough etiquette stations throughout a multihospital university medical center

text: ISSUE: In September 2003, the state health department, along with our facility, mandated that we develop a response plan for the possible re-emergence of Severe Acute Respiratory Syndrome (SARS). We convened a multidisciplinary SARS task force, and five team members were given responsibility for writing the plan. During that time, we learned that respiratory hygiene and cough etiquette guidelines were being developed by the Healthcare Infection Control Practices Advisory Committee (HICPAC). There was also a threat of a heavy early flu season, and we needed to provide easy access to hygiene supplies in all hospital and clinic waiting areas and lobbies. PROJECT: The SARS planning group came up with an idea for a “sneeze station” since our policy required that facial tissues, hand sanitizers, waste receptacles, masks, and instructional signage be readily available in all hospital and clinic lobbies and waiting rooms. We took our idea to the director of plant operations and the sneeze station concept was approved. A carpenter was assigned to develop a prototype, and after a few minor revisions by the SARS task force the sneeze station was born. Wall-mounted and rolling floor models were designed to accommodate the various space needs in our facility. It was decided that masks would not be placed on the sneeze stations, but would be available at all reception desks due to concerns of inappropriate use. Our faculty and staff were educated on the respiratory hygiene policy and sneeze stations during the February 2004 mandatory safety fair. RESULTS: As of January 2005, we have placed 180 sneeze stations in our hospitals and clinics as well as in other institutions. When new areas open, one of the first concerns is to make sure they get their sneeze stations. The sneeze stations are continuously being used based on audits of supply usage and through monitoring by the environment of care (EOC) tours. LESSONS LEARNED: The sneeze stations are accepted in the medical center as a valuable part of infection control. There are times when supply cannot keep up with demand because we only have one carpenter assigned to manufacture the sneeze stations. Another lesson learned is that placing the station in a cafeteria may result in it being used as a food disposal instead of for its intended purpose. Overall, the sneeze station has met with great success, and this proves that creative ideas can bring about change.


title: Pharyngitis

text: Abstract “Sore throat” or pharyngitis is one of the most frequent complaints of patients in the acute care setting, accounting for nearly 7 million pediatric and 6 million adult visits each year. On the surface, pharyngitis would appear to pose few challenges to the clinician; the site of infection is both visible and accessible for inspection and culture, and the majority of pharyngeal pathogens are self-limiting respiratory viruses. Unfortunately, the diagnosis and management of acute pharyngitis is complicated by the 10% to 30% of cases caused by bacterial pathogens, particularly group A beta-hemolytic streptococci (GAS). Concerns over the risk of suppurative and nonsuppurative complications associated with GAS pharyngitis have fueled the widespread practice of empirical antimicrobial therapy. However, the consequences of antimicrobial overuse, measured by cost, adverse events, and bacterial resistance, have refocused attention on the need for targeted therapy based on an appreciation of the epidemiology and diverse clinical presentations of acute pharyngitis.


title: The future of Telemedicine Cabin? The case of the French students’ acceptability()

text: Telemedicine could solve the problem of the lack of infrastructure and insufficient number of qualified healthcare staff in many countries/regions. The aim of this research is to investigate the futures of such solution by having a better understanding of the acceptance of the Telemedicine Cabin by high-educated Millennials. To reach this goal, a survey was built using specific dimensions to measure the perception of Telemedicine Cabin, the Unified-Theory-of-Acceptance-and-Use-of-Technology 2(nd) version (UTAUT2) and finally the Personal Innovativeness and the Privacy Concern scales. Our sample was composed of 158 students from different Business Schools and data were analysed using a Partial Least Approach. Findings highlight the key role of all Telemedicine Cabin dimensions (Accessibility, Availability and Compatibility) on Performance Expectancy, the importance of three UTAUT2 constructs (Performance Expectancy, Price Value and Habit) and the negative impact of Privacy Concern on the Intention to Use a Telemedicine Cabin. In addition, results demonstrate that Personal Innovativeness does not affect the Intention to Use Telemedicine Cabin.


title: Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

text: Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.


Hemoptysis in COVID-19: Observation


title: Chapter 19 Disease resistance for different livestock species

text: Abstract This chapter deals with progress in disease resistance for the livestock population species-wise and describes the progress that occurred globally. Certain genes were identified for mastitis resistance and the strategies for genomic control of mastitis are discussed. Gene-edited tuberculosis-resistant cattle were developed for the first time with CRISPR/Cas 9 technology with NRAMP gene insert. Similarly studies are in progress for the development of trypanosomiasis-resistant cattle at ILRI. Genomic insights were discussed for disease resistance for goat against gastrointestinal nematode infestation, coccidiosis, peste des petits ruminants, and scrapie. Similarly genomic resistance was also discussed for sheep, discussing the mechanism of disease resistance with MHC, antibody and T cell response, cytokines, and receptors. Genes identified for bacterial diarrhoeal resistance as K88, F18 (an intestinal receptor) for resistance to bacterial infection in pig. Gene-edited pigs were developed against porcine reproductive and respiratory syndrome and transmissible gastroenteritis caused by corona virus using CRISPR/Cas9 technology. Insights on the omics technologies developed and studied were discussed for livestock species. Genomic control on various diseases of poultry is discussed as salmonellosis, avian influenza, Marek’s disease, Newcastle disease with advanced genomic and allied techniques for its control as RNA interference, flow cytometry, quantitative polymerase chain reaction, transcriptomics, etc. A new concept on natural antibodies was discussed.


title: Recombination in Eukaryotic Single Stranded DNA Viruses

text: Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution.


title: Evaluation of a two-stage testing algorithm for the diagnosis of respiratory viral infections

text: Abstract New on-demand multiplex molecular respiratory viral diagnostics offer superior performance although can be expensive and some platforms cannot process multiple specimens simultaneously. We performed a retrospective study reviewing results of patients tested for respiratory viruses following introduction of a two-stage testing algorithm incorporating an initial screen with Sofia® immunoassay then secondary Biofire Filmarray®, and compared to a period when only Filmarray® was used. Of 2976 testing episodes, 1814 underwent initial Sofia® then follow-up FilmArray®. A diagnosis of influenza was made by Sofia® in 282 patients, and by FilmArray® in an additional 163 (median time to result 1.12hours versus 3.46hours, P <0.001). Significantly more patients received their diagnosis within 90minutes in winter despite testing more samples (11.1% versus 3.4%, P <0.001), and approximately $36,000 was saved. An algorithmic approach to respiratory viral diagnosis can combine the advantages of accuracy and speed and be cost saving.


title: Diagnostic Methods for Feline Coronavirus: A Review

text: Feline coronaviruses (FCoVs) are found throughout the world. Infection with FCoV can result in a diverse range of signs from clinically inapparent infections to a highly fatal disease called feline infectious peritonitis (FIP). FIP is one of the most serious viral diseases of cats. While there is neither an effective vaccine, nor a curative treatment for FIP, a diagnostic protocol for FCoV would greatly assist in the management and control of the virus. Clinical findings in FIP are non-specific and not helpful in making a differential diagnosis. Haematological and biochemical abnormalities in FIP cases are also non-specific. The currently available serological tests have low specificity and sensitivity for detection of active infection and cross-react with FCoV strains of low pathogenicity, the feline enteric coronaviruses (FECV). Reverse transcriptase polymerase chain reaction (RT-PCR) has been used to detect FCoV and is rapid and sensitive, but results must be interpreted in the context of clinical findings. At present, a definitive diagnosis of FIP can be established only by histopathological examination of biopsies. This paper describes and compares diagnostic methods for FCoVs and includes a brief account of the virus biology, epidemiology, and pathogenesis.


Authors’ response to letter by Fogacci, Borghi and Cicero, “Misinterpreting data in lipidology in the era of COVID-19”


title: The carbon neutrality principle: A case study in the French spirits sector

text: According to the 2019 Intergovernmental Panel on Climate Change (IPCC) report, putting in place policies that support sustainable development is imperative. The carbon neutrality concept introduced in 2002 is an efficient way to manage the risks and reduce the vulnerabilities in the land and the food system. Given the pivotal role of sustainability for todays’ consumers, the low risk and high rewards of carbon neutral production could help businesses transform their entire sector. This article is among the first to show that the carbon neutrality principle offers advantages that far outweigh the costs of maintaining the status quo. The case study of a cognac producer in France suggests that prioritizing sustainable development by reducing emissions could be a beneficial solution, particularly in the high energy spirits industry. Specifically, implementing the three stages (and substages) of the carbon neutral methodology to calculate carbon footprint, this study provides evidence that distilling 1 hL of pure alcohol produces 0.9 tons of CO(2) emissions. Proposing actions to reduce emissions by 10%, and calculating the offset costs to evaluate the remaining emissions, the study also offers a practical implementation approach and discusses several potential legislative scenarios that might accelerate the transition to carbon neutral production output.


title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus

text: Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.


title: The Severe Acute Respiratory Syndrome (SARS)-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein

text: BACKGROUND: A recent publication reported that a tyrosine-dependent sorting signal, present in cytoplasmic tail of the spike protein of most coronaviruses, mediates the intracellular retention of the spike protein. This motif is missing from the spike protein of the severe acute respiratory syndrome-coronavirus (SARS-CoV), resulting in high level of surface expression of the spike protein when it is expressed on its own in vitro. PRESENTATION OF THE HYPOTHESIS: It has been shown that the severe acute respiratory syndrome-coronavirus genome contains open reading frames that encode for proteins with no homologue in other coronaviruses. One of them is the 3a protein, which is expressed during infection in vitro and in vivo. The 3a protein, which contains a tyrosine-dependent sorting signal in its cytoplasmic domain, is expressed on the cell surface and can undergo internalization. In addition, 3a can bind to the spike protein and through this interaction, it may be able to cause the spike protein to become internalized, resulting in a decrease in its surface expression. TESTING THE HYPOTHESIS: The effects of 3a on the internalization of cell surface spike protein can be examined biochemically and the significance of the interplay between these two viral proteins during viral infection can be studied using reverse genetics methodology. IMPLICATION OF THE HYPOTHESIS: If this hypothesis is proven, it will indicate that the severe acute respiratory syndrome-coronavirus modulates the surface expression of the spike protein via a different mechanism from other coronaviruses. The interaction between 3a and S, which are expressed from separate subgenomic RNA, would be important for controlling the trafficking properties of S. The cell surface expression of S in infected cells significantly impacts viral assembly, viral spread and viral pathogenesis. Modulation by this unique pathway could confer certain advantages during the replication of the severe acute respiratory syndrome-coronavirus.


title: Pandemic influenza preparedness in the Asia–Pacific region

text: Summary Concerns are mounting that the threat of another influenza pandemic will become a reality and that the epicentre of the outbreak could be the Asia–Pacific region. We assessed the documents that some Asia–Pacific countries have published as part of preparedness planning for an outbreak of influenza in people. Regional approaches were polarised. Thailand, China, and Vietnam had set out a strategic vision to strengthen future capacity in preparedness planning. By contrast, Hong Kong, Australia, and New Zealand took a strategic approach aimed mainly at harnessing available resources or preparing for the deployment of resources such as stockpiled antiviral agents and vaccines. The plans of Hong Kong, Australia, and New Zealand compared favourably with the best European plans. The plans of resource-poor countries addressed some issues that were largely neglected by most European plans. Other countries (including those that do not yet have plans) could benefit from analysis of the strengths and weaknesses of the plans drawn up by countries in the region and in Europe.


title: Elective surgery after the pandemic: waves beyond the horizon

text: The next phase


title: Leucoefdin a potential inhibitor against SARS CoV-2 M(pro)

text: Leucoefdin an important constituent of various fruits such as banana, raspberry, etc. was explored to target M(Pro) protease of SARS Co-V 2. Ligand was found to bind at active site of M(Pro) with large negative binding energies in molecular docking and simulation study. The docking results showed that Leucoefdin interacted with the M(Pro) by forming hydrogen bonds, at Leu 141, His163, His 164, and Glu 166. Other non-bonded interactions were seen at Met49, Pro52, Tyr54, Phe140, Leu141, Cys145 and Met165. Results of Leucoefdin was in coherence with the recently reported M(Pro) protease-inhibitor complex. It even displayed better binding energies (kcal/mol) in HTVS (-6.28), SP (-7.28), XP (-9.29) and MMGBSA (-44.71) as compared to the reference ligand [HTVS (-4.87), SP (-6.79), XP (-5.75) and MMGBSA (-47.76)]. Leucoefdin-M(Pro) complex on molecular dynamic simulation showed initial fluctuations in RMSD plot for a certain period and attained equilibrium which remained stable during entire simulation for 150 ns. RMSF of protein showed less secondary structure fluctuations and a greater number of H-bond formation with Leucoefdin during 150 ns simulation. Post simulation MMGBSA analysis showed binding energy of -45.98 Kcal/mol. These findings indicated the potential of Leucoefdin as lead compound in R&D for drug discovery and development against SARS CoV-2. Communicated by Ramaswamy H. Sarma


Supraglottic Airway–Guided Intubation During the COVID-19 Pandemic: A Closed Technique


title: 2 Epstein–Barr Virus and Multiple Sclerosis Wrong Place, Wrong Time?

text: Publisher Summary Epstein–Barr virus (EBV) is a gamma-herpes-4-virus and was the first herpes virus to be completely sequenced. Several diseases are associated with EBV, including Hodgkin's and post-transplant lymphomas, oral hairy leukoplakia, and nasopharyngeal carcinomas. EBV has a double-stranded 172-kb DNA genome. Upon infection, the genome circularizes and persists as an episome in infected cells. More than 70 open reading frames exist, which encode proteins expressed during lytic and latent EBV infection. Lytic proteins encode viral proteins, which are necessary for the production of infectious virions, whereas latent proteins are needed to set up persistent infection by transforming and immortalizing host cells. EBV also encodes non-translated RNAs (e.g., EBER1 and EBER2), which are almost ubiquitously expressed and highly abundant in EBV-infected cells. Four EBV latency programs have been described with distinct sets of expressed proteins and viral RNAs: (1) Latency 0: EBER1 and EBER2 but no expression of proteins; (2) Latency 1 (true latency program): EBER1 and EBER2, EBNA1; (3) Latency 2 (default program): EBER1 and EBER2 and expression of EBNA1, latent membrane protein (LMP)-1, LMP2A, LMP2B; and (4) Latency 3 (growth program): EBER1 and EBER2 and expression of EBNA-leader protein (LP), EBNA 2–6, LMP1, LMP2A, LMP2B. The role of most EBV proteins has been characterized mainly in vitro using lymphoblastoid cell lines.


title: Foot manifestations in a patient with COVID-19 and Epstein-Barr virus: A case study

text: SARS-Cov-2 (COVID-19) is highly-contagious. It can lead to respiratory distress—and some cases—death. Recent reports and observations have identified an association between COVID-19 and manifestations in the feet. However, there are very few reports that describe the course of these foot manifestations in any detail. The authors present a case study chronicling the progression of foot issues in a COVID-19 positive patient who also was positive for the Epstein-Barr virus.


title: Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China

text: To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.


title: A sugar‐coated strategy to treat a rare neurologic disease provides a blueprint for a decoy glycan therapeutic and a potential vaccine for CoViD‐19: An Editorial Highlight for “Selective inhibition of anti‐MAG IgM autoantibody binding to myelin by an antigen specific glycopolymer”on https://doi.org/10.1111/jnc.15021

text: In a rare neurologic disease known as IgM monoclonal gammopathy the immune system targets a sulfated trisaccharide known as the Human Natural Killer‐1 (HNK‐1) epitope that comprises a constituent of the myelin sheath known as MAG (myelin‐associated glycoprotein). This Editorial highlights a study by Aliu and colleagues in the current issue of the Journal of Neurochemistry, in which the investigators constructed a biodegradable poly‐l‐lysine backbone with multiple copies of this sulfated HNK‐1 trisaccharide. This decoy, poly(phenyl disodium 3‐O‐sulfo‐β‐d‐glucopyranuronate)‐(1→3)‐β‐d‐galactopyranoside, known as PPSGG, removed anti‐MAG IgM autoantibodies from the blood, while not activating the immune system. These findings provide a path for the selective removal of a pathogenic set of antibodies that target the myelin sheath resulting in neuropathy. These findings are applicable to a parallel strategy for the generation of polysaccharides similar to those present in the receptor‐binding domain of CoViD‐19, which might inhibit viral adhesion to its receptor, the angiotensin‐converting enzyme‐2 (ACE2) protein, thereby impairing cellular uptake of the virus itself. The deployment of complex polysaccharides that mimic actual COVID19 polysaccharides on the spike protein may also provide a feasible structural basis for a vaccine. Carbohydrate mimics, if conjugated to a carrier or backbone, might provoke an immune response to the spike protein. A vaccine that targets critical carbohydrates on COVID19, and then neutralizes the virus would recapitulate a successful strategy employed in other microbial vaccines, like the pneumococcal vaccines and the meningococcal vaccines. These vaccines direct an immune response to complex carbohydrates and successfully prevent life‐threatening disease. This paper provides lessons from a rare neurologic disease that may teach us strategies applicable to a global pandemic. [Image: see text]


title: Transmission potential and severity of COVID-19 in South Korea

text: Abstract Objectives Since the first case of 2019 novel coronavirus (COVID-19) identified on Jan 20, 2020 in South Korea, the number of cases rapidly increased, resulting in 6,284 cases including 42 deaths as of March 6, 2020. To examine the growth rate of the outbreak, we aimed to present the first study to report the reproduction number of COVID-19 in South Korea. Methods The daily confirmed cases of COVID-19 in South Korea were extracted from publicly available sources. By using the empirical reporting delay distribution and simulating the generalized growth model, we estimated the effective reproduction number based on the discretized probability distribution of the generation interval. Results We identified four major clusters and estimated the reproduction number at 1.5 (95% CI: 1.4-1.6). In addition, the intrinsic growth rate was estimated at 0.6 (95% CI: 0.6, 0.7) and the scaling of growth parameter was estimated at 0.8 (95% CI: 0.7, 0.8), indicating sub-exponential growth dynamics of COVID-19. The crude case fatality rate is higher among males (1.1%) compared to females (0.4%) and increases with older age. Conclusions Our results indicate early sustained transmission of COVID-19 in South Korea and support the implementation of social distancing measures to rapidly control the outbreak.


title: The cardiac intensive care unit and the cardiac Intensivist during the COVID-19 surge in New York City()

text: Critical care cardiology has been impacted by the coronavirus disease-2019 (COVID-19) pandemic. COVID-19 causes severe acute respiratory distress syndrome, acute kidney injury, as well as several cardiovascular complications including myocarditis, venous thromboembolic disease, cardiogenic shock, and cardiac arrest. The cardiac intensive care unit is rapidly evolving as the need for critical care beds increases. Herein, we describe the changes to the cardiac intensive care unit and the evolving role of critical care cardiologists and other clinicians in the care of these complex patients affected by the COVID-19 pandemic. These include practical recommendations regarding a structural and organizational changes to facilitate care of patients with COVID-19; staffing and personnel changes; and health and safety of personnel. We draw upon our own experiences at NewYork-Presbyterian Columbia University Irving Medical Center to offer insights into the unique challenges facing critical care clinicians and provide recommendations of how to address these challenges during this unprecedented time.


title: What's in the medicine cabinet?

text: Drugs that could lessen the death toll in a flu pandemic do exist. But global stockpiles are too small, and the countries at most immediate risk are among the worst prepared. Alison Abbott reports.


title: Effect of purified immunoglobulins or pooled colostrum on performance of rearing calves

text: Abstract Fifty Belgian white-blue male calves, purchased from the market at about 10 days of age, were divided into three groups. The basic diet was the same for all calves, and consisted of a restricted amount of commercial milk replacer containing 50 ppm zinc bacitracin and 20 pm virginiamycin, calf starter and grass hay. Weaning occurred when daily starter intake over 7 consecutive days averaged 0.5 kg. Maximum starter intake was restricted to 3 kg day−1, and grass hay was fed ad libitum. The experiment lasted 20 weeks. Group 1 (control) received the basic diet. Groups 2 and 3 were supplemented with either 2 g purified immunoglobulins (Ig) or 25-ml pooled colostrum (CO) twice daily, via the milk replacer as used in Group 1. Neither Ig nor CO exerted a positive effect on growth rate and feed efficiency. Six calves died: two, one and three in Groups 1, 2 and 3, respectively. Their serum IG content was significantly lower than that of the surviving animals. Mechanisms explaining the lack of any protective effect are discussed. It is supposed that the main reason was due to the gap between the CO feeding at birth and the onset of the administration of Ig or CO at the start of the experiment. At that time, 31 of the 50 calves excreted rota-and/or coronaviruses.


title: The educational value of outpatient CL rotations- a white paper from the ACLP residency education subcommittee

text: BACKGROUND AND AIMS: As mental health services in outpatient medical clinics expand, psychiatrists must be trained to practice in these settings. The Academy of Consultation-Liaison Psychiatry (ACLP) residency education subcommittee convened a writing group with the goal of summarizing the current evidence about outpatient consultation-liaison psychiatry (CLP) training and providing a framework for CLP educators who are interested in developing outpatient CLP rotations within their programs. METHOD: MEDLINE (via PubMed), Embase and PsycINFO (via OVID), were reviewed each from inception to December 2019, for psychiatric CLP services in ambulatory settings that involved residents or fellows. The CLP education guidelines were reviewed for recommendations relevant to outpatient CLP. We also searched MedEd portal for published curriculums relevant to CLP. The group held 2 conferences to reach consensus about recommendations in setting up outpatient CLP rotations. RESULTS: Seventeen articles, three ACLP supported guidelines, and eight online didactic resources were identified as directly reporting on the organization and/or impact of an outpatient CLP rotation. These manuscripts indicated that residents found outpatient CLP rotations effective and relevant to their future careers. However, the literature provided few recommendations for establishing formal outpatient CLP training experiences. DISCUSSION: Outpatient CLP rotations offer multiple benefits for trainees, including exposure to specific clinical scenarios and therapeutic interventions applicable only in the outpatient setting, increased continuity of care and the unique experience of providing liaison and education to non-mental health providers. The article outlines recommendations and examples for developing outpatient CLP rotations which CLP educators can incorporate in their programs.


Covid-19 y esfuerzo asistencial en Atención Primaria


title: Respiratory consequences of N95-type Mask usage in pregnant healthcare workers—a controlled clinical study

text: BACKGROUND: Outbreaks of emerging infectious diseases have led to guidelines recommending the routine use of N95 respirators for healthcare workers, many of whom are women of childbearing age. The respiratory effects of prolonged respirator use on pregnant women are unclear although there has been no definite evidence of harm from past use. METHODS: We conducted a two-phase controlled clinical study on healthy pregnant women between 27 to 32 weeks gestation. In phase I, energy expenditure corresponding to the workload of routine nursing tasks was determined. In phase II, pulmonary function of 20 subjects was measured whilst at rest and exercising to the predetermined workload while breathing ambient air first, then breathing through N95-mask materials. RESULTS: Exercising at 3 MET while breathing through N95-mask materials reduced mean tidal volume (TV) by 23.0 % (95 % CI −33.5 % to −10.5 %, p < 0.001) and lowered minute ventilation (VE) by 25.8 % (95 % CI −34.2 % to −15.8 %, p < 0.001), with no significant change in breathing frequency compared to breathing ambient air. Volumes of oxygen consumption (VO(2)) and carbon dioxide expired (VCO(2)) were also significantly reduced; VO(2) by 13.8 % (95 % CI −24.2 % to −3 %, p = 0.013) and VCO(2) by 17.7 %, (95 % CI −28.1 % to −8.6 %, p = 0.001). Although no changes in the inspired oxygen and carbon dioxide concentrations were demonstrated, breathing through N95-mask materials during low intensity work (3 MET) reduced expired oxygen concentration by 3.2 % (95 % CI: −4.1 % to −2.2 %, p < 0.001), and increased expired carbon dioxide by 8.9 % (95 % CI: 6.9 % to 13.1 %; p <0.001) suggesting an increase in metabolism. There were however no changes in the maternal and fetal heart rates, finger-tip capillary lactate levels and oxygen saturation and rating of perceived exertion at the work intensity investigated. CONCLUSIONS: Breathing through N95 mask materials have been shown to impede gaseous exchange and impose an additional workload on the metabolic system of pregnant healthcare workers, and this needs to be taken into consideration in guidelines for respirator use. The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, identifier NCT00265926.


title: COVID-19: Physiopathologie d’une maladie à plusieurs visages

text: Résumé L’infection par le SARS-CoV-2, nommée COVID-19, peut conduire à une réaction immunitaire inadaptée et à une coagulopathie responsables d’un véritable sepsis viral. Dans cette revue, nous précisons les mécanismes physiopathologiques propres à chacune des phases de la COVID-19 - virale, immunitaire et pro-thrombotique - en soulignant les différentes perspectives thérapeutiques qui en découlent. Enfin, nous précisons les mécanismes physiopathologiques mis en jeu dans chaque organe dont l’atteinte a été décrite dans les études cliniques. Abstract SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.


title: Earlier detection of public health risks – Health policy lessons for better compliance with the International Health Regulations (IHR 2005): Insights from low-, mid- and high-income countries

text: Abstract The International Health Regulations (IHR 2005) require all Member States to build and maintain the capacities to prevent, detect and respond to public health emergencies. Early detection of public health risks is one of the core functions. In order to improve surveillance and detection, a better understanding of the health system conditions and their influencing factors are needed. The Israeli Ministry of Health/IHR National Focal Point held a workshop to elucidate health system conditions and their influencing factors that enable earlier detection. The workshop methodology employed a stepwise, small working group analysis approach to elucidate the conditions and their influencing factors affecting each stage of recognition, assessment, and reporting of infectious disease outbreaks, at the local, regional and national levels. In order to detect public health risks earlier, the detection process needs to be moved closer to the local communities and start with building capacity within communities. Building capacity and engaging with local and diverse communities requires significant changes in the governance approach and include information sharing, multi-sectoral communication and coordination across various levels before, during and after public health emergencies. Across the regions, low-, mid- and high-income countries seem to struggle more with governance and information sharing rather than with technical capacities and capabilities.


title: Chapter 14 Individual-Based Models for Public Health

text: Abstract Today, infectious diseases represent a threatening concern for human health. Understanding their transmission, and possibly forecasting the dynamics of these pathogens, represents both a scientific and sanitary emergency. To this goal, mathematical modeling has been a widely used tool. Nevertheless, they have important limitations to explicitly model the mechanisms involved in the infectious processes at the individual level. Thanks to the increase of computing capacity, computational models such as individual-based models (IBMs) are very relevant for understanding the complexity of mechanisms at the individual level that can be involved in disease outbreaks. Their computational formalism allows a large flexibility, while they rely on the same philosophy than current models in mathematical epidemiology that have proved their relevance. In this chapter, we review the main qualities of IBMs, what kind of new knowledge they can bring and they have already produced in epidemiological modeling. Then, we highlight their caveats and what could be developed during the future years to make IBMs a more reliable and useful approach.


title: Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013–May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities.


title: COVID-19 pandemic, oil prices, stock market, geopolitical risk and policy uncertainty nexus in the US economy: Fresh evidence from the wavelet-based approach

text: Abstract In this paper, we analyze the connectedness between the recent spread of COVID-19, oil price volatility shock, the stock market, geopolitical risk and economic policy uncertainty in the US within a time-frequency framework. The coherence wavelet method and the wavelet-based Granger causality tests applied to US recent daily data unveil the unprecedented impact of COVID-19 and oil price shocks on the geopolitical risk levels, economic policy uncertainty and stock market volatility over the low frequency bands. The effect of the COVID-19 on the geopolitical risk substantially higher than on the US economic uncertainty. The COVID-19 risk is perceived differently over the short and the long-run and may be firstly viewed as an economic crisis. Our study offers several urgent prominent implications and endorsements for policymakers and asset managers.


title: COVID-19 and the cardiovascular system

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.


title: Respiratory Syncytial Virus Outbreak in the Basic Military Training Camp of the Republic of Korea Air Force

text: OBJECTIVES: An outbreak of acute febrile illness occurred in the Republic of Korea Air Force boot camp from May to July 2011. An epidemiological investigation of the causative agent, which was of a highly infective nature, was conducted. METHODS: Throat swabs were carried out and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed to identify possible causative factors. RESULTS: The mean age of patients who had febrile illness during the study period was 20.24 years. The multiplex RT-PCR assay identified respiratory syncytial virus (RSV) as the causative agent. The main symptoms were sore throat (76.0%), sputum (72.8%), cough (72.1%), tonsillar hypertrophy (67.9%), and rhinorrhea (55.9%). The mean temperature was 38.75°C and the attack rate among the recruits was 15.7% (588 out of 3750 recruits), while the mean duration of fever was 2.3 days. The prognosis was generally favorable with supportive care but recurrent fever occurred in 10.1% of the patients within a month. CONCLUSIONS: This is the first epidemiological study of an RSV outbreak that developed in a healthy young adult group. In the event of an outbreak of an acute febrile illness of a highly infective nature in facilities used by a young adult group, RSV should be considered among the possible causative agents.


title: Chapparvovirus DNA Found in 4% of Dogs with Diarrhea

text: Feces from dogs in an unexplained outbreak of diarrhea were analyzed by viral metagenomics revealing the genome of a novel parvovirus. The parvovirus was named cachavirus and was classified within the proposed Chapparvovirus genus. Using PCR, cachavirus DNA was detected in two of nine tested dogs from that outbreak. In order to begin to elucidate the clinical impact of this virus, 2,053 canine fecal samples were screened using real-time PCR. Stool samples from 203 healthy dogs were positive for cachavirus DNA at a rate of 1.47%, while 802 diarrhea samples collected in 2017 and 964 samples collected in 2018 were positive at rates of 4.0% and 4.66% frequencies, respectively (healthy versus 2017-2018 combined diarrhea p-value of 0.05). None of 83 bloody diarrhea samples tested positive. Viral loads were generally low with average real-time PCR Ct values of 36 in all three positive groups. The species tropism and pathogenicity of cachavirus, the first chapparvovirus reported in feces of a placental carnivore, remains to be fully determined.


title: Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag

text: Abstract Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert.


title: Immunization in Travel Medicine

text: The specialty of travel medicine encompasses a broad and dynamic practice. A thorough pretravel consultation provides an individual with a comprehensive, evidence-based, contextual discussion of the risk profile for specific itinerary-based, travel-related illness and injury, allowing the traveler to use this information in conjunction with his or her personal health belief model, risk tolerance, and experience to decide on an informed management plan. This article focuses on the pretravel consultation with emphasis on the contribution of immunization to traveler’s health.


title: Human memory T cell responses to SARS-CoV E protein

text: Abstract E protein is a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV). Disruption of E protein may reduce viral infectivity. Thus, the SARS-CoV E protein is considered a potential target for the development of antiviral drugs. However, the cellular immune responses to E protein remain unclear in humans. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. Analysis of the immune responses by flow cytometry showed that both CD4+ and CD8+T cells were involved in the SARS-CoV E-specific immune responses after stimulation with SARS-CoV E peptides. Moreover, the majority of IFN-γ+CD4+T cells were central memory cells expressing CD45RO+CCR7+CD62L−; whereas IFN-γ+CD8+ memory T cells were mostly effector memory cells expressing CD45RO−CCR7−CD62L−. The results of T-cell responses to 9 individual peptides indicated that the E protein contained at least two major T cell epitopes (E2 amino acid [aa] 9–26 and E5–6: aa 33–57) which were important in eliciting cellular immune response to SARS-CoV E protein in humans.


title: Nonhuman Primate Quarantine: Its Evolution and Practice

text: Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of naïve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future.