title: A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion

text: BACKGROUND: Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network. METHODS: We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a "bulls-eye" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL"B") and calcium chloride (XL "C"). RESULTS: Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 ± 0.6 to 50.9 ± 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 μL to 150 μL of XL "B". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern. CONCLUSION: The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased "expectoration".


title: Detection of bovine coronaviruses from adult cows with epizootic diarrhea and their antigenic and biological diversities

text: Bovine coronavirus (BCV) was detected by reverse transcriptase-PCR, immune electron microscopy or virus isolation from adult cows at 6 out of 6 outbreaks of epizootic diarrhea in Japan. Six BCVs isolated in feces, intestinal content or tracheal exudate of the cows were analyzed for their antigenic properties by cross virus neutralization (VN) tests. The isolates were divided into two groups, one of which had closely related antigenicity with the reference Mebus and Kakegawa strains of BCV, and another which showed significant differences in VN antibody titers from the reference strains. Two isolates in the latter group, which were from the enteric and respiratory tracts of the same cows, respectively, were distinguished from each other by ELISA using monoclonal antibodies against the Kakegawa strain. The isolates showed various hemagglutination and receptor destroying enzyme titers against chicken or mouse erythrocytes.


title: Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints

text: [Image: see text] Knowledge of RNA structure is necessary to determine structure–function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5′ to 3′ directionality of base pairs in helices. The 5′ to 3′ directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.


Les actualités de DDS 1er trimestre 2020


docid: urnbggzs

title: Single primer isothermal amplification (SPIA) combined with next generation sequencing provides complete bovine coronavirus genome coverage and higher sequence depth compared to sequence-independent single primer amplification (SISPA)

text: Coronaviruses are of major importance for both animal and human health. With the emergence of novel coronaviruses such as SARS and MERS, the need for fast genome characterisation is ever so important. Further, in order to understand the influence of quasispecies of these viruses in relation to biology, techniques for deep-sequence and full-length viral genome analysis are needed. In the present study, we compared the efficiency of two sequence-independent approaches [sequence-independent single primer amplification (SISPA) and single primer isothermal amplification (SPIA, represented by the Ovation kit)] coupled with high-throughput sequencing to generate the full-length genome of bovine coronavirus (BCoV) from a nasal swab. Both methods achieved high genome coverage (100% for SPIA and 99% for SISPA), however, there was a clear difference in the percentage of reads that mapped to BCoV. While approximately 45% of the Ovation reads mapped to BCoV (sequence depth of 169–284 944), only 0.07% of the SISPA reads (sequence depth of 0–249) mapped to the reference genome. Although BCoV was the focus of the study we also identified a bovine rhinitis B virus (BRBV) in the data sets. The trend for this virus was similar to that observed for BCoV regarding Ovation vs. SISPA, but with fewer sequences mapping to BRBV due to a lower amount of this virus. In summary, the SPIA approach used in this study produced coverage of the entire BCoV (high copy number) and BRBV (low copy number) and a high sequence/genome depth compared to SISPA. Although this is a limited study, the results indicate that the Ovation method could be a preferred approach for full genome sequencing if a low copy number of viral RNA is expected and if high sequence depth is desired.


title: Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance

text: Abstract Microbial infections affect humans worldwide. Many quaternary ammonium compounds have been synthesized that are not only antibacterial, but also possess antifungal, antiviral and anti-matrix metalloproteinase capabilities. Incorporation of quaternary ammonium moieties into polymers represents one of the most promising strategies for preparation of antimicrobial biomaterials. Various polymerization techniques have been employed to prepare antimicrobial surfaces with quaternary ammonium functionalities; in particular, syntheses involving controlled radical polymerization techniques enable precise control over macromolecular structure, order and functionality. Although recent publications report exciting advances in the biomedical field, some of these technological developments have also been accompanied by potential toxicological and antimicrobial resistance challenges. Recent evidenced-based data on the biomedical applications of antimicrobial quaternary ammonium-containing biomaterials that are based on randomized human clinical trials, the golden standard in contemporary medicinal science, are included in the present review. This should help increase visibility, stimulate debates and spur conversations within a wider scientific community on the implications and plausibility for future developments of quaternary ammonium-based antimicrobial biomaterials.


title: Pneumonie virale sévère de l'immunocompétent

text: Résumé Les infections virales respiratoires communautaires sont fréquentes et le plus souvent bénignes. Beaucoup d'agents différents comme les virus influenza, ou para-influenza, le virus respiratoire syncitial, les rhinovirus, coronavirus, adénovirus et les herpès virus peuvent être isolés chez les patients immunocompétents. Parmi ces virus, le cytomégalovirus (CMV) peut être responsable de pneumonie nosocomiale en réanimation. Le diagnostic des infections virales est difficile car les signes cliniques sont non spécifiques et l'isolement du virus responsable difficile. Cependant, une symptomatologie clinique associant fièvre, myalgies, céphalées, pharyngite est fréquente dans les infections à Inflenza qui peuvent aboutir à des tableaux sévères. Enfin, le virus plus récent responsable d'infection respiratoire est un virus nouvellement découvert de la famille des coronavirus, le SRAS-CoV qui a été responsable d'une épidémie d'infections respiratoires sévères. Les pneumonies virales sont fréquentes mais probablement non diagnostiquées chez les patients immunocompétents. Cependant le diagnostic est nécessaire car pour la plupart des pathogènes il existe un traitement efficace. Le diagnostic repose sur l'histologie mais de nouvelles techniques comme la PCR doivent devenir d'utilisation courante pour améliorer le rendement diagnostique. Abstract Respiratory infections are frequently encountered in the community; these infections are usually associated with only minor consequences. Many different agents, such as influenza and parainfluenza virus, respiratory syncitial virus, rhinovirus, coronavirus, adenovirus and herpes virus can be found in immuno-competent patients. Among these pathogens, cytomegalovirus (CMV) has been found to be responsible for nosocomial pneumonia in ICU. The main problem for viral infections, is the diagnosis, isolation of the pathogen is often difficult and not always reliable and the symptoms not specific. However, influenza is characterised by fever, myalgia, headache and pharyngitis, this infection may be very mild, even asymptomatic, moderate or very severe. Finally, the most recent viral pathogen involved in respiratory disease is a newly discovered coronavirus, the SARS-CoV which was responsible for the worldwide outbreak of Severe Acute Respiratory Syndrome. Viral pneumonia is a common pathology which is probably underdiagnosed in immuno-competent patients; many reports show that even if the diagnosis is difficult to obtain, it is not useless as long as we have, for most of the pathogens, an effective treatment. The gold standard was histology, new techniques like PCR can probably make a difference and should be included in the guidelines to improve diagnostic efficiency.


title: More than efficacy revealed by single-cell analysis of antiviral therapeutics

text: Development of antiviral therapeutics emphasizes minimization of the effective dose and maximization of the toxic dose, first in cell culture and later in animal models. Long-term success of an antiviral therapeutic is determined not only by its efficacy but also by the duration of time required for drug-resistance to evolve. We have developed a microfluidic device comprised of ~6000 wells, with each well containing a microstructure to capture single cells. We have used this device to characterize enterovirus inhibitors with distinct mechanisms of action. In contrast to population methods, single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates reveals not only efficacy but also properties of the members of the viral population most sensitive to the drug, the stage of the lifecycle most affected by the drug, and perhaps even if the drug targets an interaction of the virus with its host.


title: Will you be covered during the next recession? Unequal safety-nets for private health insurance in the United States

text: Abstract Health insurance coverage for working-age adults in the United States is still predominantly determined by their jobs or their spouse’s jobs. This article revealed that SES disparities in access to a spouse’s coverage as a safety-net significantly contributed to the inequities in coverage loss during economic instability. Using the longitudinal Survey of Income and Program Participation (1996-2012), this article examines insurance transitions between socioeconomic groups during the two most recent recessions in the United States. The SES disparity in private coverage spiked during periods of high job-loss. Higher SES men’s and women’s coverages were barely affected as they became insured by their spouses even as they lost their own. Wives’ insurance plans played a large role in mitigating declines in higher SES men’s coverages during the 2008 recession.


title: Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus

text: Enteric diseases in swine are often caused by different pathogens and thus metagenomics are a useful tool for diagnostics. The capacities of nanopore sequencing for viral diagnostics were investigated here. First, cell culture-grown porcine epidemic diarrhea virus and rotavirus A were pooled and sequenced on a MinION. Reads were already detected at 7 seconds after start of sequencing, resulting in high sequencing depths (19.2 to 103.5X) after 3 h. Next, diarrheic feces of a one-week-old piglet was analyzed. Almost all reads (99%) belonged to bacteriophages, which may have reshaped the piglet’s microbiome. Contigs matched Bacteroides, Escherichia and Enterococcus phages. Moreover, porcine kobuvirus was discovered in the feces for the first time in Belgium. Suckling piglets shed kobuvirus from one week of age, but an association between peak of viral shedding (10(6.42)–10(7.01) copies/swab) and diarrheic signs was not observed during a follow-up study. Retrospective analysis showed the widespread (n = 25, 56.8% positive) of genetically moderately related kobuviruses among Belgian diarrheic piglets. MinION enables rapid detection of enteric viruses. Such new methodologies will change diagnostics, but more extensive validations should be conducted. The true enteric pathogenicity of porcine kobuvirus should be questioned, while its subclinical importance cannot be excluded.


title: The microarray revolution: Perspectives from educators

text: In recent years, microarray analysis has become a key experimental tool, enabling the analysis of genome‐wide patterns of gene expression. This review approaches the microarray revolution with a focus upon four topics: 1) the early development of this technology and its application to cancer diagnostics; 2) a primer of microarray research, designed to guide the beginner; 3) a highlight of the Genome Consortium for Active Teaching (GCAT), a worldwide consortium of faculty who are integrating microarrays into the undergraduate teaching laboratory; and 4) the use of microarrays in the biotechnology industry with a look forward to future applications. A central theme within this review is the profound relevance of new, bioinformatics‐based, technologies to undergraduate students within the biosciences.


title: Digital Orthopaedics. A Glimpse into the Future in The Midst of a Pandemic

text: Abstract Background The response to COVID-19 catalyzed the adoption and integration of digital health tools into the healthcare delivery model for musculoskeletal patients. The change, suspension or relaxation of Medicare and federal guidelines enabled the rapid implementation of these technologies. The expansion of payment models for virtual care facilitated its rapid adoption. The authors aim to provide several examples of digital health solutions utilized to manage orthopaedic patients during the pandemic and discuss what features of these technologies are likely to continue to provide value to patients and clinicians following its resolution. Conclusion The widespread adoption of new technologies enabling providers to care for patients remotely has the potential to permanently change the expectations of all stakeholders about the way care is provided in orthopaedics. The new era of Digital Orthopaedics will see a gradual and non-disruptive integration of technologies that support the patient’s journey through the successful management of their musculoskeletal disease.


Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19


title: Effectiveness of interventions targeting air travellers for delaying local outbreaks of SARS-CoV-2

text: BACKGROUND: We evaluated if interventions aimed at air travellers can delay local SARS-CoV-2 community transmission in a previously unaffected country. METHODS: We simulated infected air travellers arriving into countries with no sustained SARS-CoV-2 transmission or other introduction routes from affected regions. We assessed the effectiveness of syndromic screening at departure and/or arrival & traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduces the average number of secondary cases. We use stochastic simulations to account for uncertainty in both arrival and secondary infections rates, and present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. We report the median expected delay achievable in each scenario and an inner 50% interval. RESULTS: Under baseline assumptions, introducing exit and entry screening in combination with traveller sensitisation can delay a local SARS-CoV-2 outbreak by 8 days (50% interval: 3–14 days) when the rate of importation is 1 infected traveller per week at time of introduction. The additional benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by 7 days (50% interval: 2–13 days). In the absence of screening, with less effective sensitisation, or a higher rate of importation, these delays shrink rapidly to less than 4 days. CONCLUSION: Syndromic screening and traveller sensitisation in combination may have marginally delayed SARS-CoV-2 outbreaks in unaffected countries.


title: A comparison of infection control program resources, activities, and antibiotic resistant organism rates in Canadian acute care hospitals in 1999 and 2005: Pre- and post-severe acute respiratory syndrome

text: BACKGROUND: The Resources for Infection Control in Hospitals (RICH) project assessed infection control programs and rates of antibiotic-resistant organisms (AROs) in Canadian acute care hospitals in 1999. In the meantime, the severe acute respiratory syndrome (SARS) outbreak and the concern over pandemic influenza have stimulated considerable government and health care institutional efforts to improve infection control systems in Canada. METHODS: In 2006, a version of the RICH survey similar to the original RICH instrument was mailed to infection control programs in all Canadian acute care hospitals with 80 or more beds. We used χ(2), analysis of variance, and analysis of covariance analyses to test for differences between the 1999 and 2005 samples for infection control program components and ARO rates. RESULTS: 72.3% of Canadian acute care hospitals completed the RICH survey for 1999 and 60.1% for 2005. Hospital size was controlled for in analyses involving AROs and surveillance and control intensity levels. Methicillin-resistant Staphylococcus aureus (MRSA) rates increased from 1999 to 2005 (F = 9.4, P = .003). In 2005, the mean MRSA rate was 5.2 (standard deviation [SD], 6.1) per 1000 admissions, and, in 1999, it was 2.0 (SD, 2.9). Clostridium difficile-associated diarrhea rates trended up from 1999 to 2005 (F = 2.9, P = .09). In 2005, the mean Clostridium difficile-associated diarrhea rate was 4.7 (SD, 4.3), and, in 1999, it was 3.8 (SD, 4.3). The proportion of hospitals that reported having new nosocomial vancomycin-resistant Enterococcus (VRE) cases was greater in 2005 than in 1999 (χ(2) = 10.5, P = .001). In 1999, 34.5% (40/116) of hospitals reported having new nosocomial VRE cases, and, in 2005, 61.0% (64/105) reported new cases. Surveillance intensity index scores increased from a mean of 61.7 (SD, 18.5) in 1999 to 68.1 (SD, 15.4) in 2005 (F = 4.1, P = .04). Control intensity index scores trended upward slightly from a mean of 60.8 (SD, 14.6) in 1999 to 64.1 (SD, 12.2) in 2005 (F = 3.2, P = .07). Infection control professionals (ICP) full-time equivalents (FTEs) per 100 beds increased from a mean of 0.5 (SD, 0.2) in 1999 to 0.8 (SD, 0.3) in 2005 (F = 90.8, P < .0001). However, the proportion of ICPs in hospitals certified by the Certification Board of Infection Control decreased from 53% (SD, 46) in 1999 to 38% (SD, 36) in 2005 (F = 8.7, P = .004). CONCLUSION: Canadian infection control programs in 2005 continued to fall short of expert recommendations for human resources and surveillance and control activities. Meanwhile, nosocomial MRSA rates more than doubled between 1999 and 2005, and hospitals reporting new nosocomial VRE cases increased 77% over the same period. Although investments have been made toward infection control programs in Canadian acute care hospitals, the rapid rise in ICP positions has not yet translated into marked improvements in surveillance and control activities. In the face of substantial increases in ARO rates in Canada, continued efforts to train ICPs and support hospital infection control programs are necessary.


title: Passive protection of neonatal calves against bovine coronavirus-induced diarrhea by administration of egg yolk or colostrum antibody powder

text: Abstract The protective effect of egg yolk and colostrum powders prepared from hens and cows vaccinated with inactivated bovine coronavirus (BCV) antigen was evaluated in a challenge model with a virulent BCV strain. Twenty three calves from BCV-free herds were randomly divided into control and several treatment groups. All calves were orally challenged with 1 × 109 TCID50 of the virulent Kakegawa strain of BCV at 24 to 36 h after birth. Calves in treatment groups received either egg yolk powder or cow colostrum containing BCV specific antibodies. Daily treatment with these antibody preparations started 6 h until 7 days post-challenge. Control calves which received no antibody had severe diarrhea and all died within 6 days after infection. In contrast, calves fed milk containing egg yolk or colostrum with neutralization titers of 1:2560 or 1:10 240 respectively all survived and had positive weight gain unlike the other treatment groups. These results indicate that the orally administered egg yolk and colostrum powders protected against BCV-induced diarrhea in neonatal calves and that the egg yolk used provided a higher degree of protection compared to colostrum powder on a titer basis. Treatment with whole egg yolk from immunized hens therefore provides a more efficacious alternative to the existing methods of specific passive protection against BCV.


title: Analysis of helicase domain mutations in the hepatitis E virus derived from patients with fulminant hepatic failure: Effects on enzymatic activities and virus replication

text: Abstract Fulminant hepatic failure (FHF) is the severe form of hepatitis E virus infection. Virus sequence analyses from severe cases have shown presence of unique and highly conserved mutations in the helicase domain of genotype 1, 3 and 4 viruses. We evaluated role of two amino acid replacements (L1110F) and (V1120I); found to be frequent in genotype 1 FHF-E viruses from India. Three mutant helicase proteins (two with single point mutations and one with dual mutations) were expressed in Escherichia coli and evaluated for their ATPase and RNA unwinding activities. Both L1110F and V1120I helicase mutants showed marginal decrease in ATPase activity, while L1110F/V1120I dual mutant showed normal ATPase activity. All three mutants proteins showed RNA unwinding activities comparable to wild type protein. Corresponding mutations were made in the helicase domain of HEV RLuc replicon and replication efficiencies were tested in the S10-3 (Huh 7) cells. The mutant replicon V1120I showed lower replication as compared to L1110F and L1110F/V1120I mutants. However, all three replicon mutants showed lower replication efficiencies as compared to the wild type replicon. Walker A and Walker B motif mutant HEV replicons were unable to replicate indicating essential role of the virus encoded helicase domain during HEV replication. FHF-E associated helicase mutations resulted in only marginal decrease in the virus replication suggesting alternate function/s of the helicase protein. Mutations in the helicase domain of FHF-E viruses may be responsible for changing virus or host-virus protein–protein interactions, causing alterations in the host responses, eventually leading to more severe disease manifestations.


title: Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”?

text: Melatonin (N‐acetyl‐5‐methoxytryptamine) is a multifunctional signaling molecule that has a variety of important functions. Numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. Clinical trials have shown that melatonin is efficient in preventing cell damage under acute (sepsis, asphyxia in newborns) and chronic states (metabolic and neurodegenerative diseases, cancer, inflammation, aging). The beneficial effects of melatonin can be explained by its properties as a potent antioxidant and antioxidant enzyme inducer, a regulator of apoptosis and a stimulator of immune functions. These effects support the use of melatonin in viral infections, which are often associated with inflammatory injury and increases in oxidative stress. In fact, melatonin has been used recently to treat several viral infections, which are summarized in this review. The role of melatonin in infections is also discussed herein. Copyright © 2012 John Wiley & Sons, Ltd.


title: Performance of Pneumonia Severity Index and CURB-65 in Predicting 30-day mortality in patients with COVID-19

text: Abstract Objective The aim of the study was to analyze the usefulness of the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality in patients with COVID-19 and to identify other factors associated with higher mortality. Methods A retrospective study was performed at a pandemic hospital in Istanbul, Turkey and 681 laboratory-confirmed patients with COVID-19 were included. Data on characteristics, vital signs and laboratory parameters were recorded form electronic medical records. We used receiver operating characteristic analysis to quantify the discriminatory abilities of the prognostic scales. Univariate and multivariate logistic regression analyses were performed to identify other predictors of mortality. Results Higher CRP levels were associated with an increased risk for mortality (OR:1.015, 95% CI 1.008 to 1.021, p < 0.001). The PSI performed significantly better than the CURB-65 (AUC: 0.91, 95% CI 0.88-0.93 vs AUC:0.88, 95% CI:0.85-0.90; p = 0.01) and the addition of CRP levels to PSI did not improve the performance of PSI in predicting mortality (AUC: 0.91, 95% CI 0.88-0.93 vs AUC:0.92, 95% CI:0.89-0.94; p = 0.29). Conclusion In a large group of hospitalized patients with COVID-19, we found that PSI performed better than CURB-65 in predicting mortality. Adding CRP levels to PSI did not improve the 30-day mortality prediction.


title: Ranking hazards pertaining to human health concerns from land application of anaerobic digestate

text: Abstract Anaerobic digestion (AD) has been identified as one of the cleanest producers of green energy. AD typically uses organic materials as feedstock and, through a series of biological processes, produces methane. Farmyard manure and slurry (FYM&S) are important AD feedstock and are typically mixed with agricultural waste, grass and/or food wastes. The feedstock may contain many different pathogens which can survive the AD process and hence also possibly be present in the final digestate. In this study, a semi-quantitative screening tool was developed to rank pathogens of potential health concern emerging from AD digestate. A scoring system was used to categorise likely inactivation during AD, hazard pathways and finally, severity as determined from reported human mortality rates, number of global human-deaths and infections per 100,000 populations. Five different conditions including mesophilic and thermophilic AD and three different pasteurisation conditions were assessed in terms of specific pathogen inactivation. In addition, a number of scenarios were assessed to consider foodborne incidence data from Ireland and Europe and to investigate the impact of raw FYM&S application (without AD and pasteurisation). A sensitivity analysis revealed that the score for the mortality rate (S3) was the most sensitive parameter (rank coefficient 0.49) to influence the final score S; followed by thermal inactivation score (S1, 0.25) and potential contamination pathways (S2, 0.16). Across all the scenarios considered, the screening tool prioritised Cryptosporidium parvum, Salmonella spp., norovirus, Streptococcus pyogenes, enteropathogenic E. coli (EPEC), Mycobacterium spp., Salmonella typhi (followed by S. paratyphi), Clostridium spp., Listeria monocytogenes and Campylobacter coli as the highest-ranking pathogens of human health concern resulting from AD digestate in Ireland. This tool prioritises potentially harmful pathogens which can emerge from AD digestate and highlights where regulation and intervention may be required.


title: Poliovirus Replication Requires the N-terminus but not the Catalytic Sec7 Domain of ArfGEF GBF1

text: Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the Arf GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to BFA, an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism.


title: Influenza-Associated Mortality in Georgia (2009–2011)

text: We analyzed data from NCDCPH Georgia where samples from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory syndrome (SARI) are referred for testing on influenza virus using PCR analysis. During 2009-2010 and 2010-2011 influenza pandemics total number of the laboratory-confirmed influenza cases were 1286 with 33 deaths (all of them influenza type A) and 1203 (51.4% type A) with 44 deaths, respectively. At least one underlying medical condition was reported in 70.7% (for pandemic influenza strain) and 96% (for influenza type B) of deaths. Predominating preexisting condition was coronary heart disease.


title: Marburg virus-like particles by co-expression of glycoprotein and matrix protein in insect cells induces immune responses in mice

text: BACKGROUND: Marburg virus (MARV) causes severe haemorrhagic fever in humans and nonhuman primates and has a high mortality rate. However, effective drugs or licensed vaccines are not currently available to control the outbreak and spread of this disease. METHODS: In this study, we generated MARV virus-like particles (VLPs) by co-expressing the glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. MARV VLPs and three adjuvants, Poria cocos polysaccharide (PCP-II), poly(I:C) and aluminium hydroxide, were evaluated after intramuscular vaccination in mice. RESULTS: Murine studies demonstrated that vaccination with the MARV VLPs induce neutralizing antibodies and cellar immune responses. MARV VLPs and the PCP-II adjuvant group resulted in high titres of MARV-specific antibodies, activated relatively higher numbers of B cells and T cells in peripheral blood mononuclear cells (PBMCs), and induced greater cytokine secretion from splenocytes than the other adjuvants. CONCLUSION: MARV VLPs with the PCP-II adjuvant may constitute an effective vaccination and PCP-II should be further investigated as a novel adjuvant.


Prevalence of feline coronavirus


title: Recent advances in identifying and theorizing the role of immigrant entrepreneurs, ethnicity, and culture in industrial marketing

text: Abstract This special issue of Industrial Marketing Management (IMM) features four articles that cover topics related to immigrant entrepreneurs, ethnicity, and culture in industrial marketing. This introductory paper summarizes the contributions of these articles and points out future research directions.


docid: lgcmamfb

title: The Courage to Change the Rules: A Proposal for an Essential Health R&D Treaty

text: The medical needs of many of the world's population go unmet. A new treaty on essential health R&D could provide a binding framework to redirect today's scientific expertise to priority needs


title: Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs

text: [Image: see text] The suggested bat origin for Middle East respiratory syndrome coronavirus (MERS-CoV) has revitalized the studies of other bat-derived coronaviruses with respect to interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an important betacoronavirus (betaCoV) that is phylogenetically affiliated with the same genus as MERS-CoV. The bat surveillance data indicated that BatCoV HKU9 has been widely spreading and circulating in bats. This highlights the necessity of characterizing the virus for its potential to cross species barriers. The receptor binding domain (RBD) of the coronavirus spike (S) protein recognizes host receptors to mediate virus entry and is therefore a key factor determining the viral tropism and transmission capacity. In this study, the putative S RBD of BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been structurally and functionally defined, was characterized via a series of biophysical and crystallographic methods. By using surface plasmon resonance, we demonstrated that HKU9-RBD binds to neither SARS-CoV receptor ACE2 nor MERS-CoV receptor CD26. We further determined the atomic structure of HKU9-RBD, which as expected is composed of a core and an external subdomain. The core subdomain fold resembles those of other betaCoV RBDs, whereas the external subdomain is structurally unique with a single helix, explaining the inability of HKU9-RBD to react with either ACE2 or CD26. Via comparison of the available RBD structures, we further proposed a homologous intersubdomain binding mode in betaCoV RBDs that anchors the external subdomain to the core subdomain. The revealed RBD features would shed light on the evolution route of betaCoV.


title: Severe varicella-zoster virus pneumonia: a multicenter cohort study

text: BACKGROUND: Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). METHODS: This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. RESULTS: One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32–51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1–3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1–2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO(2)/FiO(2)) = 150 (80–284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33–2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08–1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00–111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7–21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections. CONCLUSIONS: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-017-1731-0) contains supplementary material, which is available to authorized users.


title: A decomposition-ensemble approach for tourism forecasting

text: Abstract With the frequent occurrence of irregular events in recent years, the tourism industry in some areas, such as Hong Kong, has suffered great volatility. To enhance the predictive accuracy of tourism demand forecasting, a decomposition-ensemble approach is developed based on the complete ensemble empirical mode decomposition with adaptive noise, data characteristic analysis, and the Elman's neural network model. Using Hong Kong tourism demand as an empirical case, this study firstly investigates how data characteristic analysis is used in a decomposition-ensemble approach. The empirical results show that the proposed model outperforms other models in both point and interval forecasts for different prediction horizons, indicating the effectiveness of the proposed approach for forecasting tourism demand, especially for time series with complexity.


title: Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study

text: BACKGROUND: A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19. METHODS: We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R(t)) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020. FINDINGS: COVID-19 transmissibility measured by R(t) has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34–53%) reduction in transmissibility in the community, from an estimated R(t) of 1·28 (95% CI 1·26–1·30) before the start of the school closures to 0·72 (0·70–0·74) during the closure weeks. Similarly, a 33% (24–43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an R(t) of 1·10 (1·06–1·12) before the start of the school closures to 0·73 (0·68–0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively. INTERPRETATION: Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020. FUNDING: Health and Medical Research Fund, Hong Kong.


title: Public Health Responses to and Challenges for the Control of Dengue Transmission in High-Income Countries: Four Case Studies

text: Dengue has a negative impact in low- and lower middle-income countries, but also affects upper middle- and high-income countries. Despite the efforts at controlling this disease, it is unclear why dengue remains an issue in affluent countries. A better understanding of dengue epidemiology and its burden, and those of chikungunya virus and Zika virus which share vectors with dengue, is required to prevent the emergence of these diseases in high-income countries in the future. The purpose of this review was to assess the relative burden of dengue in four high-income countries and to appraise the similarities and differences in dengue transmission. We searched PubMed, ISI Web of Science, and Google Scholar using specific keywords for articles published up to 05 May 2016. We found that outbreaks rarely occur where only Aedes albopictus is present. The main similarities between countries uncovered by our review are the proximity to dengue-endemic countries, the presence of a competent mosquito vector, a largely nonimmune population, and a lack of citizens’ engagement in control of mosquito breeding. We identified important epidemiological and environmental issues including the increase of local transmission despite control efforts, population growth, difficulty locating larval sites, and increased human mobility from neighboring endemic countries. Budget cuts in health and lack of practical vaccines contribute to an increased risk. To be successful, dengue-control programs for high-income countries must consider the epidemiology of dengue in other countries and use this information to minimize virus importation, improve the control of the cryptic larval habitat, and engage the community in reducing vector breeding. Finally, the presence of a communicable disease center is critical for managing and reducing future disease risks.


title: Neisseria meningitidis pneumonia with bacteremia without meningitis: an atypical presentation

text: Neisseria meningitidis remains the most important cause of bacterial meningitis worldwide. The second most common and potentially severe end-organ manifestation of invasive meningococcal disease is meningococcal pneumonia. It occurs between 5% and 15% of all patients with invasive meningococcal disease. N. meningitidis sepsis and meningitis continue to be associated with high morbidity and mortality, however, meningococcal pneumonia is uncommon and often underreported. We describe a case of sepsis secondary to pneumonia with N. meningitidis bacteremia, without any evidence of meningitis. This case reports aims at highlighting pneumonia as a presentation of N. meningitidis bacteremia, and the need for a high level of clinical suspicion to establish the diagnosis.


title: Recent insights for the emerging COVID-19: drug discovery, therapeutic options and vaccine development

text: SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population, causing over 5.5 million confirmed cases worldwide. As COVID-19 has posed a global threat with significant human casualties and severe economic losses, there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus. Although there are no specific antiviral therapies that have proven effective in randomized clinical trials, currently, the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission. Besides, global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19. Herein, the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.


title: SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in ‘lasso’ for the multi-faced virus

text: During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the least rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a ‘cytokine storm’ in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.


title: „Emerging Infectious Diseases“: Dengue-Fieber, West-Nil-Fieber, SARS, Vogelgrippe, HIV

text: Some emerging infectious diseases have recently become endemic in Germany. Others remain confined to specific regions in the world. Physicians notice them only when travelers after infection in endemic areas present themselves with symptoms. Several of these emerging infections will be explained. HIV is an example for an imported pathogen which has become endemic in Germany. SARS and avian influenza are zoonoses with the potential to spread from person to person. Avian influenza in humans provides a possibility for the reassortment of a potential new pandemic strain. Outbreaks of dengue fever in endemic areas are reflected in increased infections in travelers returning from these areas. Currently, West-Nile-virus infections are only imported into Germany. The timely implementation of diagnostic, therapeutic and infection control measures requires physicians to include these diseases in their differential diagnosis. To achieve this goal, good cooperation between physicians, laboratories and the public health service is essential.


title: Chapter 7 Coronaviridae: 100,000 Years of Emergence and Reemergence

text: Abstract The coronavirus family (Coronaviridae) is a positive-sense single-stranded RNA, with a size of 27kb. These viruses have a potential species specificity and interspecies transmission. The interspecies transmission of viruses from one host species to another is a major factor responsible for the majority of emerging and reemerging infections. The Coronaviridae is one of the most popular emerging viral families that threaten to the public health.


title: How Should U.S. Hospitals Prepare for Coronavirus Disease 2019 (COVID-19)?

text: Estimates suggest that COVID-19 will stress bed capacity, equipment, and health care personnel in U.S. hospitals in ways not previously experienced. How can health systems prepare to care for a large influx of patients with this disease?


title: Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants

text: Respiratory infections in infancy may protect against developing Th2‐mediated allergic disease (hygiene hypothesis). To estimate the relative contribution of particular viruses to the development of the immune system and allergic disease, we investigated longitudinally the prevalence of respiratory viral infections in infants. One hundred and twenty‐six healthy infants were included in this prospective birth cohort study in their first year of life. Physical examination was performed and nasal brush samples were taken during routine visits every 6 months and during an upper respiratory tract infection (URTI) (sick visits). The prevalence of respiratory viral infections in infants with URTI, infants with rhinitis without general malaise and infants without nasal symptoms was studied. Rhinovirus was the most prevalent pathogen during URTI and rhinitis in 0‐ to 2‐year‐old infants (∼40%). During URTI, also respiratory syncytial virus (∼20%) and coronavirus (∼10%) infections were found, which were rarely detected in infants with rhinitis. Surprisingly, in 20% of infants who did not present with nasal symptoms, rhinovirus infections were also detected. During routine visits at 12 months, a higher prevalence of rhinovirus infections was found in infants who attended day‐care compared with those who did not. We did not observe a relation between breast‐feeding or smoking by one or both parents and the prevalence of rhinovirus infections. The parental history of atopy was not related to the prevalence of rhinovirus infection, indicating that the genetic risk of allergic disease does not seem to increase the chance of rhinovirus infections. In conclusion, rhinovirus infection is the most prevalent respiratory viral infection in infants. It may therefore affect the maturation of the immune system and the development of allergic disease considerably.


title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies

text: SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation. Those effects, together with the “cytokine storm” are involved in a worse prognosis. In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host’s cells and tissues. By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases. Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme. Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients? Do they act on multiple cell types? Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes. At present, insufficient detailed data from trials have been made available.


title: Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

text: In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.


title: A convenient colorimetric assay for the quantification of porcine epidemic diarrhea virus and neutralizing antibodies

text: Abstract Neonatal enteritis caused by the porcine epidemic diarrhea virus (PEDV) is an important cause of high mortality and economic losses to the swine industry. Virus neutralization (V/N) assays are commonly requested in diagnostic laboratories for the assessment of protective antibodies. However, the visual assessment of viral cytopathic effects by operators to determine antibody titers or for viral quantification is a tedious, subjective and time-consuming process, especially when high volume testing is involved. To improve the ease of testing, a colorimetric virus neutralization and TCID50 assays were developed and validated in this study using (3-(4,5-dimethylthiazol-2-yl) Tr-2,5-diphenyltetrazolium- bromide) (MTT), a colorimetric agent which measures cell viability. The respective conventional assays were used as the gold standards. An OD cut off value of ≤0.53, selected by receiver operating characteristics analysis, could distinguish between wells with and without CPE accurately. Performance and reproducibility parameters of the colorimetric assays were comparable to the conventional assays. The described methods can reduce testing time in diagnostic laboratories, while significantly improving current protocols.


An Invited Commentary on: Emergency and Essential Surgical Healthcare Services during COVID-19 in Low- And Middle-Income Countries: a Perspective


title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012

text: In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.


Management and outcomes of a Vascular Surgery Department with sudden medical staff outbreak of COVID-19


title: Chapter 34 The Experimental Use of Syrian Hamsters

text: The Syrian hamster (Mesocricetus auratus) possesses a variety of unique features which make them desirable research models. Despite these features, experimental use of the hamster has declined over the past 20–30 years. The current chapter will focus on research and literature describing the experimental use of the hamster with a particular emphasis on research done since the previous edition of this text (1987–present).


title: Vascularites associées aux infections virales

text: Résumé Des virus, causes de vascularites Si la plupart des vascularites systémiques sont de cause inconnue, la responsabilité d’une infection virale a été démontrée de façon formelle pour certaines d’entre elles, un traitement spécifique pouvant les guérir définitivement. Chaque virus incriminé rend compte d’un type particulier de vascularite. Infection par le virus de l’hépatite B (VHB) Elle est la cause de la périartérite noueuse dans 36 à 50 % des cas. La symptomatologie apparaît de façon aiguë, en général dans les mois suivant l’infection; elle est comparable à celle observée en l’absence d’infection par VHB. Cryoglobulinémies liées au virus de l’hépatite C (VHC) Les manifestations cliniques sont celles d’une vascularite systémique avec un tropisme plus particulier pour la peau (atteinte le plus souvent inaugurale et presque constante), les nerfs périphériques, les glomérules. Elles surviennent assez tardivement au décours de l’infection. Vascularites associées à l’infection par le VIH (virus de l’immunodéficience humaine) Il existe un fort tropisme pour le système nerveux périphérique (multinévrites) et central. Au cours de l’infection aiguë par le Parvovirus B19 Des lésions de vascularite ont été parfois signalées après la phase virémique, se limitant généralement à une ou plusieurs poussées de pupura vasculaire prédominant aux membres inférieurs. Après infection par le virus varicelle-zona Une vascularite se développe parfois, sous la forme d’un déficit neurologique central (déficit moteur avec ou sans aphasie environ un mois après un zona ophtalmologique), d’une atteinte de la rétine, plus rarement de la peau ou des reins. Vascularites associées à l’infection par le cytomégalovirus (CMV) Survenant essentiellement chez le sujet immunodéprimé, les vascularites après infection par le CMV sont diffuses intéressant surtout le tube digestif, en particulier le côlon, le système nerveux central et la peau. Une complication rare de l’infection à HTLV1 (Human T-cell Lymphoma Virus) Une vascularite rétinienne prenant volontiers la forme d’une rétinite nécrosante est souvent associée à une paraparésie spasmodique. Stratégie thérapeutique Pour de nombreuses vascularites d’origine virale, les traitements corticoïdes et immunosuppresseurs ne sont indiqués qu’en seconde intention en cas d’échec des antiviraux et de l’association d’antiviraux et d’échanges plasmatiques. Summary Viruses, the cause of vasculitis Although the majority of systemic vasculitis are of unknown causes, the responsibility of a viral infection has been formally demonstrated in some of them and specific treatment can permanently cure them. Each virus incriminated accounts for a particular type of vasculitis. Hepatitis B viral infection (HBV) is the cause of polyarteritis nodosa in 36 to 50% of cases. The onset of the symptomatology is acute, usually within a few months following the infection; it is comparable to that observed in the absence of HBV infection. Cryoglobulinemia related to the hepatitis C virus (HCV) The clinical manifestations are those of systemic vasculitis with particular tropism for the skin (involvement generally inaugural and almost constant), peripheral nerves and the glomerula. They occur fairly late during the infection. Vasculitis associated with HIV infection There is strong tropism for the peripheral (multi-neuritis) and central nervous system. During acute parvovirus B19 infection Vasculitis lesions have occasionally been reported following the viremic phase, generally limited to one or several flares of vascular purpura predominating on the lower limbs. Following varicella-herpes zoster infection Vasculitis occasionally develops in the form of a central neurological deficiency (locomotor deficiency with or without aphasia around one month after an ophthalmologic herpes zoster) or involving the retina or, more rarely, the skin or the kidneys. Vasculitis associated with cytomegaloviral infection Predominantly observed in immunodepressed patients, vasculitis after CMV infection is diffuse and basically involving the digestive tube, notably the colon, the central nervous system and the skin. A rare complication of an HTLV1 infection Vasculitis of the retina often in the form of necrotic retinitis is often associated with spasmodic paraparessia. Therapeutic strategy For many vasculitis of viral origin, corticosteroid and immunosuppressive treatments are only indicated in second intention following failure with antiviral agents and the combination of antivirals and plasma exchanges.


title: Influenza virus RNA recovered from droplets and droplet nuclei emitted by adults in an acute care setting

text: Transmission in hospital settings of seasonal influenza viruses and novel agents such as the Middle East respiratory syndrome coronavirus (MERS-CoV) is well-described but poorly understood. The characterization of potentially infectious bio-aerosols in the healthcare setting remains an important yet ill-defined factor in the transmission of respiratory viruses. Empiric data describing the distribution of bio-aerosols enable discernment of potential exposure risk to respiratory viruses. We sought to determine the distribution of influenza virus RNA emitted into the air by participants with laboratory-confirmed influenza, and whether these emissions had the potential to reach healthcare workers’ breathing zones. Two-stage cyclone bio-aerosol samplers from the Centers for Disease Control and Prevention – National Institute for Occupational Safety and Health were placed 0.5–1.0 m (near field) and 2.1–2.5 m (far field) from infected patient participants, as well as in the corridor immediately outside their rooms. In addition, healthcare worker participants providing care to infected participants were recruited to wear a polytetrafluoroethylene (PTFE) filter cassette in their breathing zones. Viral RNA was detected from the air emitted by 37.5% of the 16 participants infected with influenza virus and distributed both in near and far fields and in all tested particle sizes (<1 µm, 1–4 µm, and >4 µm). Viral RNA was recovered in droplet nuclei and beyond 1 m from naturally-infected participants in the healthcare setting and from the breathing zone of one healthcare worker. There was no correlation between patient participant nasal viral load and recovery of viral RNA from the air, and we did not identify any significant association between RNA detection from the air and patient demographics or clinical presentation. A more substantial study is required to identify patient determinants of virus emission into the air and delineate implications for evidence-based policy for prevention and control.


title: Evaluation of the Cadi ThermoSENSOR Wireless Skin-Contact Thermometer Against Ear and Axillary Temperatures in Children

text: The Cadi ThermoSENSOR skin-contact thermometer measures body temperature continuously and transmits readings wirelessly to a central server. This study evaluated the ThermoSENSOR against ear temperatures (ETs) measured by a Braun ThermoScan ear thermometer and axillary temperatures (ATs) measured by a Terumo digital clinical thermometer. The test participants consisted of 109 children aged 6 months to 16 years from a pediatric ward. The sensor was attached to the lower abdomen at least 15 minutes before the first measurement. ET, AT, and ThermoSENSOR temperatures (TTs) were recorded up to three times at the usual measurement times. The TTs differed from ETs by −0.23°C ± 0.47°C (mean ± standard deviation, n = 271) and from ATs by +0.21°C ± 0.46°C (n = 270). The ETs differed from ATs by +0.43°C ± 0.42°C (n = 315). These results suggest that the TTs were comparable to the ETs and ATs.


Une enquête sur le rôle joué par les pharmaciens d’officine durant la crise sanitaire


title: Public Perceptions of Hospital Responsibilities to Those Presenting Without Medical Injury or Illness During a Disaster

text: Abstract Background During natural and manmade disasters, the hospital is perceived as a central rallying and care site for the public, for both those with and without emergency medical needs. The expectations of the public may outstrip hospital plans and abilities to provide nonmedical assistance. Objective Our objective was to determine the public expectations of the hospital during disasters regarding resource provision. Methods A survey was distributed to adult patients or family members at three emergency departments (EDs). Respondents were asked to evaluate hospital responsibility to provide nine resources to those without emergency medical needs, including vaccination, medication refill or replacement, food and water, grief/stress counseling, Federal Emergency Management Agency (FEMA) access assistance, short/long-term shelter, family reunification, and hospital. Additionally, respondents answered questions regarding prior disaster experience and demographics. Results There were 961 respondents (66.9% were female, 47.5% were white, and 44.6% were black). Respondents agreed or strongly agreed that the hospital should provide the following services: event-specific vaccination (84%), medication refill/replacement (76.5%), food and water (61%), grief or stress counseling (53%), FEMA access assistance (52%), short-term shelter (51%), family reunification (50%), long-term shelter (38%), and hospital transportation (29%). Those 36–45 years of age were less likely to expect services (p < 0.05) and non-whites and those with a family member with a medical condition requiring electricity were more likely to expect services (p < 0.001 and p < 0.05, respectively). There were no differences based on frequency of ED use, sex, income, or prior disaster experience. Conclusion There is a high public expectation that hospitals will provide significant nonmedical disaster relief. Understanding these expectations is essential to appropriate community disaster planning.


title: Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen

text: Despite the current pandemic season, reports on pathologic features of coronavirus disease 19 (Covid-19) are exceedingly rare at the present time. Here we describe the pathologic features of early lung involvement by Covid-19 in a surgical sample resected for carcinoma from a patient who developed SARS-CoV-2 infection soon after surgery. The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels, and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes. These features are similar to those previously described in SARS-CoV-2 infection. Subtle histologic changes suggestive pulmonary involvement by Covid-19 may be accidentally encountered in routine pathology practice, especially when extensive sampling is performed for histology. These findings should be carefully interpreted in light of the clinical context of the patient and could prompt a pharyngeal swab PCR test to rule out the possibility of SARS-CoV-2 infection in asymptomatic patients.


Intersection of Gene Therapy and Progenitor Cell Biology in the Lung


title: Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes

text: OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.


SARS virus claims its third victim in Canada


title: Coronavirus infection of polarized epithelial cells

text: Abstract Epithelial cells are the first host cells to be infected by incoming coronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for the directional sorting of coronaviruses might be similar to those governing the polar release of secretory proteins.


title: Helping Couples in the Shadow of COVID‐19

text: The pandemic caused by the SARS‐CoV‐2 virus (coronavirus) and the associated illness, COVID‐19, has caused a level of worldwide upheaval unlike any most people now living have seen in their lifetimes. This crisis affects people in their most important, committed, and intimate relationships. Although this crisis has damaged the health and well‐being of individuals, crushed economies, and led to an extensive period of uncertainty about the future, there may also be positive outcomes in the motivation people have to protect their relationships. In this paper, we focus on strategies that therapists and relationship educators can use to help couples preserve and protect their relationships during such a time. We describe four foundations of safety that allow relationships to thrive: physical, emotional, commitment, and community. We then highlight three keys from our body of work that can help guide individuals and couples in protecting their relationships on a day‐to‐day and moment‐to‐moment basis: (1) decide, don’t slide; (2) make it safe to connect; (3) do your part.


title: Report from the World Health Organization's Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 7–9th Sep 2015

text: Abstract There are more vaccines in development, against a greater number of pathogens, than ever before. A challenge with this exceptional level of activity and investment is how to select and resource the most promising approaches to have the most significant impact on public health. The WHO Product Development for Vaccines Advisory Committee (PDVAC) was established in 2014 to provide strategic advice and recommendations to WHO for vaccines in clinical development that could have a significant impact on public health in low and middle income countries. On 7–9th September 2015, PDVAC was convened for the second time, when the committee reviewed vaccine developments in 24 disease areas. This report summarises the key recommendations from that consultation.


title: Establishment of a Porcine Parvovirus (PPV) LAMP Visual Rapid Detection Method

text: Porcine parvovirus (PPV) is one of the major causes of reproductive pig disease. Due to its serious nature, wide spread and consequent great damage to the swine industry, an effective, rapid and convenient method for its detection is needed. A loop-mediated isothermal amplification (LAMP) assay was established to detect PPV infection. Two pairs of primers were specifically designed to recognize the six different sequences of open reading frame1 (ORF1) gene. The optimized LAMP program was as follows: 50 min at 59 °C followed by 3 min at 80 °C.The amplified products were analyzed both by visual inspection after staining with SYBR Green I dye and by conventional agarose gel electrophoresis. Both methods showed the same sensitivity. The limit of detection (LOD) for PPV by LAMP was 10 copies, which is 100-fold lower than conventional PCR. Our LAMP assay did not cross-react with other viruses. We used the established LAMP system to test 1100 field samples and detected 660 positives. The LAMP detection method for PPV represents a visual, sensitive and rapid assay which can detect the virus in the field, offering an attractive alternative for the PPV detection methods currently in use.


title: Pharmaceutical Prescription in Canine Acute Diarrhoea: A Longitudinal Electronic Health Record Analysis of First Opinion Veterinary Practices

text: Canine acute diarrhoea is frequently observed in first opinion practice, though little is known about commonly used diagnostic or therapeutic management plans, including use of antimicrobials. This retrospective observational study utilised electronic health records augmented with practitioner-completed questionnaires from 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between April 2014 and January 2017. We used multivariable analysis to explore factors potentially associated with pharmaceutical agent prescription, and resolution of clinical signs by 10 days post-initial presentation. Use of bacteriological and/or parasitological diagnostic tests were uncommon (3.2% of cases, 95% confidence interval, CI, 2.4–4.0), though systemic antimicrobials were the most commonly prescribed pharmaceutical agents (49.7% of cases, 95% CI 46.1–53.2). Such prescription was associated with haemorrhagic diarrhoea (odds ratio, OR, 4.1; 95% CI 3.4–5.0), body temperature in excess of 39.0°C, or moderate/severe cases (OR 1.3, 95% CI 1.1–1.7). Gastrointestinal agents (e.g., antacids) were prescribed to 37.7% of cases (95% CI 35.4–39.9), and were most frequently prescribed to vomiting dogs regardless of presence (OR 46.4, 95% CI 19.4–110.8) or absence of blood (OR 17.1, 95% CI 13.4–21.9). Endoparasiticides/endectocides were prescribed to 7.8% of cases (95% CI 6.8–9.0), such prescription being less frequent for moderate/severe cases (OR 0.5, 95% CI 0.4–0.7), though more frequent when weight loss was recorded (OR 3.4, 95% CI 1.3–9.0). Gastrointestinal nutraceuticals (e.g., probiotics) were dispensed to 60.8% of cases (95% CI 57.1–64.6), these cases less frequently presenting with moderate/severe clinical signs (OR 0.6, 95% CI 0.5–0.8). Nearly a quarter of cases were judged lost to follow-up (n=754). Insured (OR 0.7, 95% CI 0.5–0.9); neutered (OR 0.4, 95% CI 0.3–0.5), or vaccinated dogs (OR 0.3, 95% CI 0.3–0.4) were less commonly lost to follow-up. Of remaining dogs, clinical signs were deemed resolved in 95.4% of cases (95% CI 94.6–96.2). Provision of dietary modification advice and gastrointestinal nutraceuticals alone were positively associated with resolution (OR 2.8, 95% CI 1.3–6.1); no such associations were found for pharmaceutical agents, including antimicrobials. Hence, this study supports the view that antimicrobials are largely unnecessary for acute diarrhoea cases; this being of particular importance when considering the global threat posed by antimicrobial resistance.


title: Predictors of viral pneumonia: The need for viral testing in all patients hospitalized for nursing home‐acquired pneumonia

text: AIM: Community‐acquired pneumonia (CAP) is presumed to be bacterial in origin and empirical antibiotics are almost always given on admission. However, early detection of viral infection is also very important for hospital infection control and timely use of antiviral agents. The present study aimed to compare patients with viral and bacterial pneumonia, and identify independent predictors of viral pneumonia. METHODS: A prospective cohort study was carried out in a tertiary teaching hospital in a 1‐year period. Older patients (aged ≥65 years) were recruited if they were admitted for CAP confirmed by chest radiographs. RESULTS: A cohort of 488 patients was analyzed. Infective causes were found in 137 (28.1%) patients. Bacterial, viral and mixed infections were detected in 86 (17.6%), 41 (8.4%) and 10 (2.0%) patients, respectively. Bacteriology was established mostly by sputum culture and virology by nasopharyngeal aspirate (NPA) viral culture. The commonest bacterial isolates were Haemophilus influenzae (31), Pseudomonas aeruginosa (15), Mycobacterium tuberculosis (14), Klebsiella spp. (9) and Streptococcus pneumoniae (6). Influenza A virus (28, 8 were pandemic 2009 A/H1N1 subtype) and respiratory syncytial virus (16) were the most frequent viral causes. Independent predictors of viral pneumonia included nursing home residence (RR 3.056, P = 0.009) and absence of leukocytosis (RR 0.425, P = 0.026). CONCLUSIONS: All nursing home residents hospitalized for CAP should undergo NPA viral testing because of infection control, early antiviral treatment and discharge planning. We suggest that empirical antiviral agents might be considered for nursing home residents hospitalized for CAP if outbreaks of influenza‐like illness are reported in nursing homes. Geriatr Gerontol Int 2013; 13: 949–957.


title: Higher-Order Analysis of Probabilistic Long-Term Loss under Nonstationary Hazards

text: Abstract Quantification of hazard-induced losses plays a significant role in risk assessment and management of civil infrastructure subjected to hazards in a life-cycle context. A rational approach to assess long-term loss is of vital importance. The loss assessment associated with stationary hazard models and low-order moments (i.e., expectation and variance) has been widely investigated in previous studies. This paper proposes a novel framework for the higher-order analysis of long-term loss under both stationary and nonstationary hazards. An analytical approach based on the moment generating function is developed to assess the first four statistical moments of long-term loss under different stochastic models (e.g., homogeneous Poisson process, non-homogeneous Poisson process, renewal process). Based on the law of total expectation, the developed approach expands the application scope of the moment generating function to nonstationary models and higher-order moments (i.e., skewness and kurtosis). Furthermore, by employing the convolution technique, the proposed approach effectively addresses the difficulty of assessing higher-order moments in a renewal process. Besides the loss analysis, the mixed Poisson process, a relatively new stochastic model, is introduced to consider uncertainty springing from the stochastic occurrence rate. Two illustrative examples are presented to demonstrate practical implementations of the developed approach. Ultimately, the proposed framework could aid the decision-maker to select the optimal option by incorporating higher-order moments of long-term loss within the decision-making process.


title: Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

text: BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease. DESIGN: Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology. RESULTS: All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence. CONCLUSIONS: These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.


title: Novel and established intestinal cell line models – An indispensable tool in food science and nutrition

text: This review presents the applications of intestinal cell models of human and pig origin in food and nutritional sciences and highlights their potential as in vitro platforms for preclinical research. Intestinal cell models are used in studies of bioavailability, adsorption and transport in nutritional or toxicological settings, allergic effects of food components, as well as probiotics and/or host–pathogen gut interactions. In addition, this review discusses the advantages of using specialized and functional cell models over generic cancer-derived cell lines.


title: A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models

text: We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.


title: Suicide and Lyme and associated diseases

text: PURPOSE: The aim of this paper is to investigate the association between suicide and Lyme and associated diseases (LAD). No journal article has previously performed a comprehensive assessment of this subject. INTRODUCTION: Multiple case reports and other references demonstrate a causal association between suicidal risk and LAD. Suicide risk is greater in outdoor workers and veterans, both with greater LAD exposure. Multiple studies demonstrate many infections and the associated proinflammatory cytokines, inflammatory-mediated metabolic changes, and quinolinic acid and glutamate changes alter neural circuits which increase suicidality. A similar pathophysiology occurs in LAD. METHOD: A retrospective chart review and epidemiological calculations were performed. RESULTS: LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital–urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year. CONCLUSION: Suicidality seen in LAD contributes to causing a significant number of previously unexplained suicides and is associated with immune-mediated and metabolic changes resulting in psychiatric and other symptoms which are possibly intensified by negative attitudes about LAD from others. Some LAD suicides are associated with being overwhelmed by multiple debilitating symptoms, and others are impulsive, bizarre, and unpredictable. Greater understanding and a direct method of acquiring LAD suicide statistics is needed. It is suggested that medical examiners, the Centers for Disease Control and Prevention, and other epidemiological organizations proactively evaluate the association between LAD and suicide.


title: Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera

text: Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay.


title: Testing for multiple bubbles in the copper price: Periodically collapsing behavior

text: Abstract This study investigates whether multiple bubbles exist in the copper price on the basis of the Generalized Supremum Augmented Dickey-Fuller (GSADF) approach (Phillips et al., 2013). This technique delivers date-stamping strategies for the emergence as well as collapse of explosive bubble episodes and is best suited for practical application to time series. The results reveal that four explosive bubbles are detected over the period of 1980–2019 when copper price deviates from fundamental value. Besides, this finding is in accordance with the asset pricing model (Gürkaynak, 2008), which generally considers both fundamental and bubble components in the presence of asset prices. Based on the empirical results, the multiple emergence and collapse of multiple price bubbles are attributed to speculation, depreciation of the U.S. dollar, an imbalance between supply and demand, and financial crises. Policymakers should actively recognize bubble episodes and monitor their evolution, which could be conducive to achieving the effective stabilization of the international copper price. To reduce excess price fluctuations and explosive copper bubbles, authorities should impose restrictions on excessive speculative behaviors under extreme market conditions.


title: ID: 101 Investigating the role of interferon λ4 in hepatitis C virus infection

text: IFNL4, a recently discovered member of the interferon λ family (IFNλs or type III IFNs), is a pseudogene in a significant fraction of the human population. A single nucleotide polymorphism located in IFNL4, which determines the ability to express IFNλ4, has been correlated with poor spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infections. We show that IFNλ4 is an active type III IFN that induces a typical subset of ISGs, signals through the classical type III IFN receptor complex and is antiviral against HCV and coronaviruses. However, its secretion is impaired and this impairment is caused by a yet unknown molecular determinant, but appears to be partially caused by a weak signal peptide and inefficient N-linked glycosylation. This glycosylation is not required for antiviral activity and secretion of IFNλ4, but seems to improve its processing. The impaired secretion of IFNλ4 appears to be a recently acquired feature of primates. A single amino acid substitution in IFNλ4 changing a proline at position 70 to a serine (P70S) alters its activity. We demonstrate that the IFNλ4-S70 variant has a significantly lower antiviral activity compared to IFNλ4-P70. Our subsequent genetic study on a cohort of patients infected with HCV shows that individuals, who encode IFNλ4-S70, display lower hepatic ISG expression, better treatment response rates and better spontaneous clearance rates than patients encoding IFNλ4-P70. This study provides important evidence supporting a role for active IFNλ4 as the driver of high hepatic ISG expression as well as the cause of poor HCV clearance.