title: Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London

text: BACKGROUND: The United Kingdom is experiencing an increase in drug-related deaths and serious bacterial infections among its most vulnerable citizens. Cuts to essential services, coupled with a growing homeless population, create a challenging environment to tackle this public health crisis. In this paper, we highlight an underexplored environmental constraint faced by people living and injecting drugs on the streets. Access to water for injection is restricted in the UK, due to legislative and financial barriers. Austerity measures, such as public toilet closures, further restrict the ability of people made homeless to access clean water and protect themselves from health harms. METHODS: We generated questionnaire (n = 455) and in-depth qualitative interview (n = 32) data with people who inject drugs in London for the Care and Prevent study. Participants provided detail on their life history; drug use, injecting and living environments; health conditions and care seeking practices. FINDINGS: A high proportion of the survey sample reported lifetime history of street homelessness (78%), bacterial infections (65%) and related hospitalisation (30%). Qualitative accounts highlight unsafe, potentially dangerous, injection practices in semi-public spaces. Multiple constraints to sourcing sterile water for injection preparation were reported. Alternatives to sterile water included puddle water, toilet cistern water, whisky, cola soda and saliva. Participants who injected heroin and crack cocaine together unanimously reported adding water at two stages during injection preparation: first, adding water as a vehicle for heroin (which was then heated); second, adding cold water to the heroin mixture prior to adding the crack cocaine. This new finding of a stage addition of solvent may represent an additional risk of infection. CONCLUSION: Currently, harm reduction equipment and resources for safe injecting are not meeting the needs of people who inject drugs who are street homeless or unstably housed. Preparation of injections with non-sterile water sources could precipitate bacterial and fungal infections, particularly when used without the application of heat. It is crucial that water for injection, also skin cleaning, is made available for the unstably housed and that harm reduction messaging is tailored to speak to the everyday realities of people who prepare and inject drugs in public spaces.


title: Multiple sclerosis: Possible immunological mechanisms

text: Abstract Multiple sclerosis is the principal demyelinating disease of the central nervous system. Although the prevalence of the disease is moderately low, averaging about 40 cases per 100,000 people in high risk areas, it is a particularly devastating disease. It primarily affects young adults, is chronic, and has an unpredictable course. Most discouraging, the cause of the disease is not known and an effective treatment has not been identified. Recently, however, research has yielded some important findings concerning the etiology of MS. Much evidence now points to an immunological process as one of the major elements in the disease. It is also likely that an environmental influence, possibly an infectious process, may contribute to the disease. Finally, it is now certain that genetic makeup influences susceptibility to the disease. At present, the strongest evidence is for a polygenic effect, not the effect of a single gene or gene locus. This review will examine some of the possible immunologically mediated disease processes that could be involved in MS, especially those that could account for a role for infectious and genetic factors in the disease.


title: Leçons et perspectives concernant la prise en charge des grippes sévères depuis 2009

text: Résumé Depuis la pandémie grippale de 2009, la prise en charge des grippes sévères en réanimation a évolué : modalité de ventilation mécanique, utilisation des inhibiteurs de la neuramidase, recours précoces à l’assistance respiratoire extracorporelle. De nombreux états organisent des réseaux de surveillance épidémiologiques et un réseau de soins autour de centres référents et d’unités mobiles d’assistance. La lutte contre la grippe nosocomiale associe isolement et vaccination des personnels. Summary Since 2009 pandemic influenza, the management of severe flu has evolved in intensive care units: mechanical ventilation modalities, use of antiviral agents, early support with extracorporeal membrane oxygenation. Many countries are implementing epidemiologic monitoring and health care networks including ECMO centers. Patient's isolation and influenza vaccination prevent nosocomial outbreak of influenza.


title: Hypoglycemia at the time of Covid-19 pandemic

text: BACKGROUND: Hypoglycemia is the limiting factor in the glycemic management of diabetes, which need to be addressed critically to avoid complications. Lockdown because of new coronavirus strain (COVID-19) pandemic has further complicated the issue of hypoglycemia due to limitations in access to food, outpatient clinics, pathological services and medicines. AIM: To assess the factors associated with the risk of hypoglycemia during April–May 2020 lockdown in people with type 2 diabetes mellitus. METHODOLOGY: We analyzed the data retrospectively from 146 patients of type 2 diabetes mellitus (T2DM) reporting to the emergency department (ED) during lockdown period with symptoms suggestive of hypoglycemia. RESULTS: The majority of patients were male (90/146) with a mean age of 59.88 ± 10.09 years and a mean random blood glucose level of 57.67 ± 9.00 mg/dL. Two-third of patients (70.83%) had level 1 hypoglycemia, while level 2 hypoglycemia was reported in 29.16% of patients. A combination of Metformin and Sulfonylureas (SU) was most commonly associated with the risk of hypoglycemia (65.75%) followed by insulin (33.56%). Subjects who received insulin reported a lower blood glucose value (50.75 ± 8.20 mg/dL) as compared to those receiving a combination of metformin and SU (60.95 ± 7.10 mg/dl). 330.56% of patients who had received prophylaxis hydroxychloroquine (HCQ) 400 mg twice a day along with the routine anti-hyperglycemic agents without their dose adjustment reported hypoglycemia. Patients with hypertension, micro-vascular, macro-vascular complications, and coexistent with each other had a higher propensity to the risk of hypoglycemia (46.58%, 33.56%, 23.29%, and 32.88%) respectively. CONCLUSION: The COVID-19 lockdown has shown to influence the risk of hypoglycemia in patients with T2DM, especially those receiving SU, insulin, HCQ especially in patients with associated co-morbidities. Patient education, support, and telemedicine plays a pivotal role to prevent hypoglycemia.


title: FilmArray respiratory panel assay: An effective method for detecting viral and atypical bacterial pathogens in bronchoscopy specimens

text: Abstract The BioFire FilmArray Respiratory Panel (FA RP) is a rapid multiplexed molecular assay approved for detection of viral and atypical bacterial pathogens in nasopharyngeal specimens. This study aimed to evaluate the performance of the BioFire FilmArray Respiratory Panel v1.7 on bronchoscopy specimens. We tested 133 bronchial specimens (87 archived and 46 prospectively collected) with the FA RP and compared the results to the Luminex NxTAG Respiratory Pathogen Panel (NxTAG RPP). After discordant analysis, 123 specimens gave concordant results using the FA RP and the NxTAG RPP for an overall agreement of 93.9% (kappa = 0.88 [95% CI 0.80–0.96]), a positive percent agreement of 93.7% (95% CI 83.7–97.7) and a negative percent agreement of 94.1% (95% CI 84.9–98.1). In conclusion, the BioFire FilmArray RP performed reliably to detect a broad range of respiratory pathogens in bronchoscopy specimens.


title: Peptides from the SARS-associated coronavirus as tags for protein expression and purification

text: Abstract Protein tagging with a peptide is a commonly used technique to facilitate protein detection and to carry out protein purification. Flexibility with respect to the peptide tag is essential since no single tag suites all purposes. This report describes the usage of two short peptides from the SARS-associated coronavirus nucleocapsid (SARS-N) protein as protein tags. Plasmids for the generation of tagged proteins were generated by ligating synthetic oligonucleotides for the peptide-coding regions downstream of the protein coding sequence. The data show recognition of prokaryotically expressed HIV-1 Gag/p24 fusion protein by Western blot and efficient affinity purification using monoclonal antibodies against the tags. The SARS peptide antibody system described presents an alternative tagging opportunity in the growing field of protein science.


title: The Application Of Plasmapheresis For Covid‐19 Patients

text: Coronaviruses are known human and animal pathogens, but a novel type of coronavirus, designated as severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2) is defined by World Health Organisation(WHO).This novel type has created a pandemia throughout the world most notably causing death owing to pneumonia.Nowadays the entire world is searching the curative treatment but outcomes are discouraging for intensive care critical patients. In this article we'd like to highlight that plasmapheresis,although it’ s an unproven strategy, could be a useful approach by the mechanism of alleviating the cytokine storm and decreasing the viral load. This article is protected by copyright. All rights reserved.


title: The impact of the activities of Ghana AIDS Commission on new HIV infections in Ghana: An intervention time series analysis

text: Abstract The study examines the impact of Ghana AIDS Commission (GAC) activities on new HIV infections. Secondary data from 1 January 1996 to 31 December 2007 were obtained from the Ghana National AIDS Control Programme and Biostatistics Department of the Health Ministry. Intervention time series analysis was applied separately to the data from the northern and southern sectors due to data collection mechanism and location of two tertiary teaching hospitals. The impact of GAC activities is measured by the statistical significance of the coefficients of the intervention variable. The intervention variable is coded as zero (0) for the period before and one (1), the period after the GAC activities commenced. It was shown that the HIV incidence in the northern follows an integrated moving average model, whilst in the southern sectors an autoregressive integrated moving average model was the appropriate model. No significant impact of GAC activities was observed in the northern sector. In contrast the GAC activities in the southern sector were associated with a reduction in new HIV infections (male=−0.20±0.13, p <0.05; female=0.14±0.10, p <0.05), corresponding to a 15% and 18% reduction in male and female new HIV infections respectively in the sector. It can therefore be concluded that the GAC activities were a success. However, greater focus of GAC efforts in the northern sector is required to ensure that its activities have an impact on the incidence there.


title: Phylogenetic analysis of human coronavirus NL63 circulating in Italy

text: Abstract Background Five known human coronaviruses infect the human respiratory tract: HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63 and HCoV-HKU1. Objectives To evaluate the prevalence of HCoV-NL63 in hospitalized adult patients and to perform molecular characterization of Italian strains. Study Design HCoV-NL63 was sought by RT-PCR in 510 consecutive lower respiratory tract (LRT) samples, collected from 433 Central-Southern Italy patients over a 1-year period. Phylogenetic analysis was performed by partial sequencing of S and ORF1a. Additional S sequences from Northern Italy were included in the phylogenetic trees. Results HCoV-NL63 was detected in 10 patients (2.0%) with symptomatic respiratory diseases, mainly during winter. Phylogenetic analysis indicated a certain degree of heterogeneity in Italian isolates. The ORF1a gene clustering in phylogenetic trees did not match with that of the S gene. Conclusions As observed by others, HCoV-NL63 is often associated with another virus. Phylogenetic characterization of HCoV-NL63 circulating in Italy indicates that this virus circulates as a mixture of variant strains, as observed in other countries.


title: Using Biosecurity Measures to Combat Respiratory Disease in Cattle: The Norwegian Control Program for Bovine Respiratory Syncytial Virus and Bovine Coronavirus

text: Bovine respiratory disease (BRD) cause important health problems in all cattle husbandry systems. It contributes substantially to the use of antimicrobial substances and compromises animal welfare and the sustainability of the cattle industry. The existing preventive measures of BRD focus at the individual animal or herd level and include vaccination, mass treatment with antimicrobials and improvement of the animal's environment and general health status. Despite progress in our understanding of disease mechanism and technological development, the current preventive measures are not sufficiently effective. Thus, there is a need for alternative, sustainable strategies to combat the disease. Some of the primary infectious agents in the BRD complex are viruses that are easily transmitted between herds such as bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV). This conceptual analysis presents arguments for combatting BRD through improved external biosecurity in the cattle herds. As an example of a population-based approach to the control of BRD, the Norwegian BRSV/BCoV control-program is presented. The program is voluntary and launched by the national cattle industry. The core principle is classification of herds based on antibody testing and subsequent prevention of virus-introduction through improved biosecurity measures. Measures include external herd biosecurity barriers and regulations in the organization of animal trade to reduce direct and indirect transmission of virus. Improved biosecurity in a large proportion of herds will lead to a considerable effect at the population level. Positive herds are believed to gain freedom by time if new introduction is avoided. Vaccination is not used as part of the program. Dissemination of information to producers and veterinarians is essential. We believe that reducing the incidence of BRD in cattle is essential and will lead to reduced antimicrobial usage while at the same time improving animal health, welfare and production. Alternative approaches to the traditional control measures are needed.


title: Infections in travellers returning to Turkey from the Arabian peninsula: a retrospective cross-sectional multicenter study

text: Mass gatherings pooling people from different parts of the world—the largest of which is to Mecca, Saudi Arabia, for Hajj—may impose risks for acquisition and dissemination of infectious diseases. A substantial number of pilgrims to Hajj and Umrah are Turkish citizens (456,000 in 2014) but data are lacking on scale of the problem. We did a retrospective cross-sectional multicenter study in Turkey to explore the range of infections among inpatients who had recently returned from the Arabian Peninsula. Our inclusion criteria were patients who had acquired an infection during their trip to an Arabian Peninsula country, or who became symptomatic within 1 week of their return. The data were collected retrospectively for January 1, 2013 and March 1, 2015. 185 Turkish patients were recruited to the study across 15 referral centers with travel associated infectious diseases after returning from Arabian Peninsula countries (predominantly Saudi Arabia 163 [88.1 %] for religious purposes 162 [87.5 %]). Seventy four (40.0 %) of them were ≥ 65 years old with numerous comorbidities including diabetes (24.3 %) and COPD (14.1 %). The most common clinical diagnosis was respiratory tract infections (169 [91.5 %]), followed by diarrheal diseases (13 [7 %]), and there was one case of MERS-CoV. Patients spent a median of 5 (3–7) days as hospital inpatients and overall mortality was 1.1 %. Returning travellers from the Arabian Peninsula present as inpatients with a broad range of infectious diseases similar to common community acquired infections frequently seen in daily medical practices in Turkey.


title: Characteristics of primary Sjögren’s syndrome related lymphocytic interstitial pneumonia

text: OBJECTIVE: This paper is aimed at investigating the clinical characteristics of primary Sjogren’s syndrome (pSS) with lymphocytic interstitial pneumonia (LIP). METHODS: The demographic data, clinical manifestations, laboratory and radiological findings, treatment, and prognosis from 15 cases of pSS-LIP patients were retrospectively analyzed. The data were compared with t test, χ(2) test, and Pearson/Spearman correlation analysis. RESULTS: (1) Fifteen cases of patients with pSS-LIP are all females (100%). Compared with pSS with interstitial lung disease(pSS-ILD) patients, the incidence of dry cough, dental caries is higher in pSS-LIP patients. The incidence of shortness of breath, weight loss, and crackles is lower in pSS-LIP patients than that of pSS-ILD patients. (2) Compared with pSS-ILD patients, pSS-LIP patients had higher percentage of patients with ANA, anti-SSA52KD antibody, anti-SSA60KD antibody, and anti-SSB antibody, and the higher concentration of serum globulin. (3) Compared with pSS-ILD patients, the frequency of obstructive ventilation dysfunction is significantly higher and the frequency of diffusion dysfunction is significantly lower in pSS-LIP patients. (4) The most frequent HRCT findings in patients with pSS-LIP is cysts (100%), followed by ground-glass opacities (73.3%), nodular shadow (73.3%) among the pSS-LIP patients. Compared with PSS-ILD patients, the incidence of pulmonary nodule shadow is significantly higher in PSS-LIP patients, while that of grid shadow was significantly lower. (5) Compared with the baseline, the sum of the number, maximum diameter, and diameter of cysts in three levels of pSS-LIP patients showed an increasing trend after treatment. (6) Correlation analysis: The changes of ground-glass opacities were positively correlated with using GC or not, and those were negatively correlated with the dose of GC treatment. Besides, there is a positive correlation between the annual change rate of the maximum diameter of cysts (△Ømax1/t) and the use of CTX; there is a positive correlation between the annual change rate of the total diameter of cysts (△Øsum1/t) and the use of CTX. CONCLUSION: To the patients of pSS-LIP, female were more common than male, and the onset of LIP was usually more insidious. Hyperglobulinemia and anti-SSA antibody were more prominent in patients with pSS-LIP. Pulmonary function showed the higher rate of obstructive ventilation dysfunction and the lower rate of diffusion dysfunction. The appearance of ground-glass opacities in pSS-LIP patients suggests that the infiltration of inflammatory cells increases, which may cause airway compression, the expansion of terminal bronchioles, and the formation of cysts. The more ground-glass opacities appear earlier, and the more appearance of new cysts later. Therapy with glucocorticoid may be effective on the ground-glass opacity during acute stage, and therapy with cyclophosphamide may be effective on the cysts during chronic stage. The heavier ground-glass opacity is at baseline, the more likely it will recur during maintenance treatment. So follow-up closely is needed.


Reply to Letter to the Editor “Comfort and compliance with the use of facemasks during COVID-19 infection”


title: Modification of simian virus 40 large tumor antigen by glycosylation

text: Abstract The SV40-encoded transforming protein, large tumor antigen (T-ag), is multifunctional. Chemical modifications of the T-ag polypeptide may be important for its multifunctional capacity. T-ag is additionally modified by glycosylation. T-ag was metabolically labeled in SV40-infected cells with tritiated galactose or glucosamine, but not with mannose or fucose. The identity of glycosylated T-ag was established by immunoprecipitation with a variety of T-ag-specific antisera, including monoclonal antibodies. Incorporation of labeled sugar into T-ag was inhibited in the presence of excess unlabeled sugars, but not in the presence of excess unlabeled amino acids. Labeled monosaccharides could be preferentially removed from T-ag with a mixture of glycosidic enzymes. In addition, galactose was removed from purified T-ag by acid hydrolysis and identified as such by thin-layer chromatography. T-ag oligosaccharides were resistant to treatment with EndoH, and glycosylation was not inhibited by tunicamycin. Together, these data strongly suggest that T-ag is glycosylated. Several characteristics, including lack of mannose labeling, EndoH resistance, and tunicamycin resistance, suggest that T-ag is not an N-linked glycoprotein. Rather, these properties are more consistent with the identification of T-ag as an O-linked glycoprotein.


title: Phage M13KO7 detection with biosensor based on imaging ellipsometry and AFM microscopic confirmation

text: Abstract A rapid detection and identification of pathogens is important for minimizing transfer and spread of disease. A label-free and multiplex biosensor based on imaging ellipsometry (BIE) had been developed for the detection of phage M13KO7. The surface of silicon wafer is modified with aldehyde, and proteins can be patterned homogeneously and simultaneously on the surface of silicon wafer in an array format by a microfluidic system. Avidin is immobilized on the surface for biotin-anti-M13 immobilization by means of interaction between avidin and biotin, which will serve as ligand against phage M13KO7. Phages M13KO7 are specifically captured by the ligand when phage M13KO7 solution passes over the surface, resulting in a significant increase of mass surface concentration of the anti-M13 binding phage M13KO7 layer, which could be detected by imaging ellipsometry with a sensitivity of 109 pfu/ml. Moreover, atomic force microscopy is also used to confirm the fact that phage M13KO7 has been directly captured by ligands on the surface. It indicates that BIE is competent for direct detection of phage M13KO7 and has potential in the field of virus detection.


New tools to battle emerging viruses


title: Infection control practices among hospital health and support workers in Hong Kong

text: Summary A report by the Hong Kong government noted that hospital infection control standards were inadequate, requiring audit, development and implementation. In addition, hospital staff needed training in infection control measures. We investigated infection control practices among 162 hospital health workers (109 nurses, 45 doctors and 8 therapists) and 44 support workers in one acute hospital and two rehabilitation hospitals using a non-blinded, observational design. We examined compliance with isolation precautions and infection control guidelines, including proper wearing of a mask, goggles/face shield, or gown; handling patient care equipment, linen, and laundry; routine and terminal cleaning; and terminal cleaning of an isolation room. One major breakdown in compliance was use of sleeveless disposable plastic aprons instead of long-sleeved gowns during procedures likely to generate splashes or sprays of blood and body fluids. In more than half of the observed episodes, participants failed to disinfect medical devices, such as stethoscopes, before re-use. Thorough cleansing of commodes between patients was also lacking. Overall compliance with local and international infection control guidelines was satisfactory, but several aspects required improvement.


title: The Healthy Infant Nasal Transcriptome: A Benchmark Study

text: Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort.


title: Embracing telemedicine into your otolaryngology practice amid the COVID-19 crisis: An invited commentary

text: The COVID-19 pandemic has quickly and radically altered how Otolaryngologists provide patient care in the outpatient setting. Continuity of care with established patients as well as establishment of a professional relationship with new patients is challenging during this Public Health Emergency (PHE). Many geographic areas are under “stay at home” or “shelter in place” directives from state and local governments to avoid COVID-19 exposure risks. Medicare has recently allowed “broad flexibilities to furnish services using remote communications technology to avoid exposure risks to health care providers, patients, and the community.” [1] The implementation of telemedicine, or virtual, services, will help the Otolaryngologists provide needed care to patients while mitigating the clinical and financial impact of the pandemic. The significant coding and billing issues related to implementing telemedicine services are discussed to promote acceptance of this technology by the practicing Otolaryngologist. Of particular importance, outpatient visit Current Procedural Terminology® codes (99201-99215) may be used for telehealth visits performed in real-time audio and video.


title: CHAPTER 21 The Widespread Evolutionary Significance of Viruses

text: ABSTRACT In the last 30 years, the study of virus evolution has undergone a transformation. Originally concerned with disease and its emergence, virus evolution had not been well integrated into the general study of evolution. This chapter reviews the developments that have brought us to this new appreciation for the general significance of virus evolution to all life. We now know that viruses numerically dominate all habitats of life, especially the oceans. Theoretical developments in the 1970s regarding quasispecies, error rates, and error thresholds have yielded many practical insights into virus–host dynamics. The human diseases of HIV-1 and hepatitis C virus cannot be understood without this evolutionary framework. Yet recent developments with poliovirus demonstrate that viral fitness can be the result of a consortia, not one fittest type, a basic Darwinian concept in evolutionary biology. Darwinian principles do apply to viruses, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution distinguish virus evolution from classical studies. The available phylogenetic tools have greatly aided our analysis of virus evolution, but these methods struggle to characterize the role of virus populations. Missing from many of these considerations has been the major role played by persisting viruses in stable virus evolution and disease emergence. In many cases, extreme stability is seen with persisting RNA viruses. Indeed, examples are known in which it is the persistently infected host that has better survival. We have also recently come to appreciate the vast diversity of phage (DNA viruses) of prokaryotes as a system that evolves by genetic exchanges across vast populations (Chapter 10). This has been proposed to be the “big bang” of biological evolution. In the large DNA viruses of aquatic microbes we see surprisingly large, complex and diverse viruses. With both prokaryotic and eukaryotic DNA viruses, recombination is the main engine of virus evolution, and virus host co-evolution is common, although not uniform. Viral emergence appears to be an unending phenomenon and we can currently witness a selective sweep by retroviruses that infect and become endogenized in koala bears.


title: Eosinophilic fibrosing gastritis and toxoplasmosis in a cat

text: A 3-year-old, neutered male Tiffany cat was presented to the Animal Health Trust for investigation of pyrexia and a gastric lesion. Radiography and ultrasound showed severe thickening of the gastric wall and regional lymphadenopathy. There was altered gastric wall layering, predominately due to muscularis thickening. Histopathology confirmed eosinophilic fibrosing gastritis. The cat also had evidence of generalised Toxoplasma gondii infection, which may have been responsible for the gastric changes.


title: Molecular Detection of Adenoviruses, Rhabdoviruses, and Paramyxoviruses in Bats from Kenya

text: We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus.


title: A purified recombinant baculovirus expressed capsid protein of a new astrovirus provides partial protection to runting–stunting syndrome in chickens

text: Abstract A new viral sequence likely belonging to a virus of the family Astroviridae was determined using the gut content of chickens affected with the runting–stunting syndrome (RSS) in chickens. Since the appropriate virus could not be isolated in cell culture the open reading frame of the viral capsid protein was cloned to generate a recombinant baculovirus. The protein was purified and used as an experimental vaccine in broiler breeders to provide maternal derived antibodies for the protection of the offspring. The presence of specific antibodies was monitored by an ELISA. The offspring of vaccinated breeder hens were partially protected in a RSS challenge model.


title: Mobilization of Telepsychiatry in Response to COVID-19—Moving Toward 21(st) Century Access to Care

text: The COVID-19 pandemic threatens to disrupt the provision of mental health services. In response, policymakers, administrators, and providers have taken bold steps toward enabling telepsychiatry to bridge this sudden gap in care for our most vulnerable populations. With rapid deregulation and adoption of this modality of care, careful consideration of issues related to policy and implementation is essential to maximize its effectiveness and mitigate unintended consequences. Though the crisis places the healthcare system under strain, it sets the stage for a lasting shift in not only how care is delivered, but also our beliefs around the system’s capacity for rapid, innovative change.


title: Detection of Spliced mRNA from Human Bocavirus 1 in Clinical Samples from Children with Respiratory Tract Infections

text: Human bocavirus 1 (HBoV1) is a parvovirus associated with respiratory tract infections (RTIs) in children, but a causal relation has not yet been confirmed. To develop a qualitative reverse transcription PCR to detect spliced mRNA from HBoV1 and to determine whether HBoV1 mRNA correlated better with RTIs than did HBoV1 DNA, we used samples from HBoV1 DNA–positive children, with and without RTIs, to evaluate the test. A real-time reverse transcription PCR, targeting 2 alternatively spliced mRNAs, was developed. HBoV1 mRNA was detected in nasopharyngeal aspirates from 33 (25%) of 133 children with RTIs but in none of 28 controls (p<0.001). The analytical sensitivity and specificity of the test were good. Our data support the hypothesis that HBoV1 may cause RTIs, and we propose that HBoV1 mRNA could be used with benefit, instead of HBoV1 DNA, as a diagnostic target.


title: Genetic Analysis

text: Genetic analysis of sequence data is central to determining the evolutionary history and molecular epidemiology of viruses, particularly those such as influenza A virus that have complex ecosystems involving multiple hosts. Here we provide an outline of routine phylogenetic analyses of influenza A viruses including multiple sequence alignment, selecting the best-fit evolutionary model and phylogenetic tree reconstruction using Neighbor joining, Maximum likelihood, and Bayesian inference.


title: Approaching community priorities in youth sports injury prevention research

text: BACKGROUND: Research in youth sports is often complex. As interest in youth sports injury prevention grows, scientists should consider community priorities beyond a specific research study. MAIN TEXT: This commentary discusses the authors’ personal experiences researching concussion prevention in middle school sports, as the overarching community faced multiple challenges. These challenges included a series of weather-related emergencies that resulted in a shift in the community’s priorities, multi-day school closures, and cancellations of sports activities and meetings. We discuss the importance of considering community priorities and providing support as scientists, colleagues, and members of the communities in which we conduct research. CONCLUSION: Scientists should consider the changing circumstances and dynamics surrounding community priorities in order to help drive their research-based decisions and ensure successful and respectful applications of research based on community values and priorities.


title: Construction, expression and antiviral activity analysis of recombinant adenovirus expressing human IFITM3 in vitro

text: Abstract Interferon-inducible transmembrane protein 3 (IFITM3) inhibits the replication of multiple pathogenic viruses by blocking their entry. In this study, we constructed a shuttle plasmid, harboring human IFITM3. Thereafter, recombinant adenovirus rAd5-IFITM3 was obtained by co-transfection of the linearized viral backbone vector pAd5 and the shuttle plasmid. The results showed that human IFITM3 did not affect the assembly and morphogenesis of progeny adenovirus. Human IFITM3 can be expressed in both A549 and MDCK cells in a time dependent manner. Furthermore, cells infected with rAd5-IFITM3 at a multiplicity of infection (MOI) of 100 for 24 h were challenged with avian influenza virus (AIV) H5N1 at an MOI of 1 for 6, 12 and 24 h. Rates of H5N1 infection in rAd5-IFITM3 cells were significantly decreased at 24 h post-infection (hpi), in a time dependent manner, compared with that of wild type wtAd5-infected cells. The expressions of viral genes were significantly inhibited at transcriptional and translational levels at 6 and 12 hpi. These results suggest that IFITM3 can suppress H5N1 replication in the early stage of the infection, which may be used as a promise agent against H5N1 infection in vivo.


title: Pandemic Recovery Using a Covid-Minimal Cancer Surgery Pathway

text: Abstract The Covid-19 pandemic has created unprecedented disruption in health care delivery around the world. In an effort to prevent hospital-acquired Covid-19 infections, most hospitals have severely curtailed elective surgery, performing only surgeries if the patient’s survival or permanent function would be compromised by a delay in surgery. As hospitals emerge from the pandemic, it will be necessary to progressively increase surgical activity at a time when hospitals continue to care for Covid-19 patients. In an attempt to mitigate the risk of nosocomial infection, we have created a patient care pathway designed to minimize risk of exposure of patients coming in to the hospital for scheduled procedures. The “Covid-minimal surgery pathway” is a predetermined patient flow, that dictates the locations, personnel and materials that come in contact with our cancer surgery population, designed to minimize risk for virus transmission. We outline the approach that allowed a large academic medical center to create a Covid-minimal cancer surgery pathway within 7 days of initiating discussions. Although the pathway represents a combination of recommended practices, there is not data to support its efficacy. We share the pathway concept and our experience so that others wishing to similarly align staff and resources towards the protection of patients, may have an easier time navigating the process.


title: Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

text: Publisher Summary This chapter discusses the chemical and biological aspects of Narcissus alkaloids. Numerous alkaloids have been isolated from Narcissus speciesasaresult of the continuing search for novel alkaloids with pharmacological activity in the Amaryllidaceae family. The alkaloids isolated from this genus, classified in relation to the different skeleton types. The different Narcissus wild species and intersectional hybrids, grouped into subgenera and sections, with their corresponding alkaloids, arranged according to their ring system are listed. The biosynthetic pathways of Narcissus alkaloids includes: (1) enzymatic preparation of the precursors, (2) primary cyclization mechanisms, (3) enzymatic preparation of intermediates, (4) secondary cyclization, diversification, and restructuring. The chapter discusses proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), and mass spectrometry (MS) for Narcissus alkaloids. A list of the different Narcissus alkaloids, their spectroscopic properties, and literature with the most recent spectroscopic data is given. Several Narcissus extracts shows the following activities: antiviral, prophage induction, antibacterial, antifungal, antimalarial, insecticidal, cytotoxic, antitumor, antimitotic, antiplatelet, hypotensive, emetic, acetylcholine esterase inhibitory, antifertility, antinociceptive, chronotropic, pheromone, plant growth inhibitor, and allelopathic.


title: The ubiquitin-proteasome system in spongiform degenerative disorders

text: Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.


title: Identification of Group 1 Coronavirus Antigen in Multisystemic Granulomatous Lesions in Ferrets (Mustela putorius furo)

text: Summary Tissues from nine ferrets with granulomatous lesions similar to those seen in feline infectious peritonitis were examined histopathologically and immunohistochemically. Four main types of lesions were observed: diffuse granulomatous inflammation on serosal surfaces; granulomas with areas of necrosis; granulomas without necrosis; and granulomas with neutrophils. Other less commonly seen lesions were granulomatous necrotizing vasculitis and endogenous lipid pneumonia. FCV3-70 monoclonal antibody produced immunolabelling of group 1 coronavirus antigen in tissue samples from eight animals, the antigen being present in the cytoplasm of macrophages in the different types of granulomatous lesions.


title: SARS in the intensive care unit

text: Approximately 20% of patients with severe acute respiratory syndrome (SARS) develop respiratory failure that requires admission to an intensive care unit (ICU). Old age, comorbidity, and elevated lactate dehydrogenase on hospital admission are associated with increased risk for ICU admission. ICU admission usually is late and occurs 8 to 10 days after symptom onset. Acute respiratory distress syndrome occurs in almost all admitted patients and most require mechanical ventilation. ICU admission is associated with significant morbidity, particularly an apparent increase in the incidence of barotrauma and nosocomial sepsis. Long-term mortality for patients admitted to the ICU ranges from 30% to 50%. Many procedures in ICUs pose a high risk for transmission of SARS coronavirus to health care workers. Contact and airborne infection isolation precautions, in addition to standard precautions, should be applied when caring for patients with SARS. Ensuring staff safety is important to maintain staff morale and delivery of adequate services.


title: Genome trimming by Borna disease viruses: Viral replication control or escape from cellular surveillance?

text: Persistence of RNA viruses is frequently associated with non-uniform terminal nucleotide deletions at both ends of the viral genome, which are believed to restrict viral replication and transcription during persistent infection. Borna disease virus (BDV), a negative strand RNA virus with no recognizable acute phase, quickly establishes persistence. We recently demonstrated that the vast majority of BDV genomes and antigenomes possess uniformly trimmed 5′ termini, even if the virus is recovered from complementary DNA encoding a hypothetical full-length viral genome. Here we discuss different mechanisms which might lead to the selective 5′-terminal trimming of the BDV genome and subsequent retrieval of the lost genetic information. We further discuss possible benefits of genome trimming in the light of recent findings that terminal RNA structures are recognized by intracellular sensors which trigger innate immunity. We hypothesize that 5′-terminal genome trimming might represent a smart strategy of BDV to evade the antiviral host response.


title: NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Trypanosoma cruzi Acute Infection

text: Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T. cruzi-Tulahuen strain acute infection. We demonstrated that infected nlrp3−/− and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of nlrp3−/− mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and nlrp3−/− mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, caspase-1/11−/− mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, caspase-1/11−/− mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation.


title: Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish

text: BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.


title: Multiplex SYBR Green and duplex TaqMan real-time PCR assays for the detection of Photorhabdus Insect-Related (Pir) toxin genes pirA and pirB

text: Abstract Acute hepatopancreatic necrosis disease (AHPND), also known as Early mortality syndrome (EMS), is a recently emerged lethal disease that has caused major economic losses in shrimp aquaculture. The etiologic agents are Vibrio spp. that carry Photorhabdus Insect-Related (Pir) toxin genes pirA and pirB. A multiplex SYBR Green real-time PCR was developed that detects pirA, pirB, and two internal control genes, the shrimp 18S rRNA and the bacterial 16S rRNA genes in a single reaction. The pirB primers amplify the 3'-end of the pirB gene allowing the detection of Vibrio spp. mutants that contain a complete deletion of pirA and the partial deletion of pirB. The assay also detects mutants that contain the entire pirA gene and the deletion of the pirB gene. Since both toxin genes are needed for disease development, this assays can distinguish between pathogenic strains of Vibrio spp. that cause AHPND in shrimp and mutants that do not cause disease. The amplicons for pirA, pirB, 18S rRNA and 16S rRNA showed easily distinguishable melting temperatures of 78.21 ± 0.18, 75.20 ± 0.20, 82.28 ± 0.34 and 85.41 ± 0.21 °C respectively. Additionally, a duplex real-time PCR assay was carried out by designing TaqMan probes for the pirA and pirB primers. The diagnostic sensitivity and specificity was compared between the SYBR Green and TaqMan assays. Both assays showed similar sensitivity with a limit of detection being 10 copies for pirA and pirB, and neither assays showed any cross reaction with other known bacterial and viral pathogens in shrimp. The high sensitivity of both assays make them suitable for the detection of low copies of the pirA and pirB genes in AHPND causing Vibrio spp. as well as for detecting non-pathogenic mutants.


title: The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold

text: Abstract The transcription and replication of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is regulated by specific viral genome sequences within 5′- and 3′-untranslated regions (5′-UTR and 3′-UTR). Here we report the solution structure of 5′-UTR derived stem-loop 2 (SL2) of SARS-CoV determined by NMR spectroscopy. The highly conserved pentaloop of SL2 is stacked on 5-bp stem and adopts a canonical CUYG tetraloop fold with the 3′ nucleotide (U51) flipped out of the stack. The significance of this structure in the context of a previous mutagenesis analysis of SL2 function in replication of the related group 2 coronavirus, mouse hepatitis virus, is discussed.


title: Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

text: Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection and hospitalization in infants. In spite of the enormous clinical burden caused by RSV infections, there remains no efficacious RSV vaccine. CD8 T cells mediate viral clearance as well as provide protection against a secondary RSV infection. However, RSV-specific CD8 T cells may also induce immunopathology leading to exacerbated morbidity and mortality. Many of the crucial functions performed by CD8 T cells are mediated by the cytokines they produce. IFN-γ and TNF are produced by CD8 T cells following RSV infection and contribute to both the acceleration of viral clearance and the induction of immunopathology. To prevent immunopathology, regulatory mechanisms are in place within the immune system to inhibit CD8 T cell effector functions after the infection has been cleared. The actions of a variety of cytokines, including IL-10 and IL-4, play a critical role in the regulation of CD8 T cell effector activity. Herein, we review the current literature on CD8 T cell responses and the functions of the cytokines they produce following RSV infection. Additionally, we discuss the regulation of CD8 T cell activation and effector functions through the actions of various cytokines.


title: Surge capacity of intensive care units in case of acute increase in demand caused by COVID‐19 in Australia

text: OBJECTIVES: To assess the capacity of intensive care units (ICUs) in Australia to respond to the expected increase in demand associated with COVID‐19. DESIGN: Analysis of Australian and New Zealand Intensive Care Society (ANZICS) registry data, supplemented by an ICU surge capability survey and veterinary facilities survey (both March 2020). SETTINGS: All Australian ICUs and veterinary facilities. MAIN OUTCOME MEASURES: Baseline numbers of ICU beds, ventilators, dialysis machines, extracorporeal membrane oxygenation machines, intravenous infusion pumps, and staff (senior medical staff, registered nurses); incremental capability to increase capacity (surge) by increasing ICU bed numbers; ventilator‐to‐bed ratios; number of ventilators in veterinary facilities. RESULTS: The 191 ICUs in Australia provide 2378 intensive care beds during baseline activity (9.3 ICU beds per 100 000 population). Of the 175 ICUs that responded to the surge survey (with 2228 intensive care beds), a maximal surge would add an additional 4258 intensive care beds (191% increase) and 2631 invasive ventilators (120% increase). This surge would require additional staffing of as many as 4092 senior doctors (245% increase over baseline) and 42 720 registered ICU nurses (269% increase over baseline). An additional 188 ventilators are available in veterinary facilities, including 179 human model ventilators. CONCLUSIONS: The directors of Australian ICUs report that intensive care bed capacity could be near tripled in response to the expected increase in demand caused by COVID‐19. But maximal surge in bed numbers could be hampered by a shortfall in invasive ventilators and would also require a large increase in clinician and nursing staff numbers.


title: Computational modeling of the p7 monomer from HCV and its interaction with small molecule drugs

text: Hepatitis C virus p7 protein is a 63 amino acid polytopic protein with two transmembrane domains (TMDs) and one of the prime targets for anti HCV drug development. A bio-inspired modeling pathway is used to generate plausible computational models of the two TMDs forming the monomeric protein model. A flexible region between Leu-13 and Gly-15 is identified for TMD1(1-32) and a region around Gly-46 to Trp-48 for TMD2(36-58). Mutations of the tyrosine residues in TMD2(36-58) into phenylalanine and serine are simulated to identify their role in shaping TMD2. Lowest energy structures of the two TMDs connected with the loop residues are used for a posing study in which small molecule drugs BIT225, amantadine, rimantadine and NN-DNJ, are identified to bind to the loop region. BIT225 is identified to interact with the backbone of the functionally important residues Arg-35 and Trp-36. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-324) contains supplementary material, which is available to authorized users.


title: Organ Transplantation, Risks☆

text: Abstract Viruses are among the most common causes of opportunistic infection after solid organ and hematopoietic stem cell transplantation (SOT and HSCT). Viral infection is associated with both direct (invasive disease) and indirect (immune modulation) effects affecting susceptibility to other infections and promoting allograft rejection. The transplantation recipient is susceptible to a broad array of viral pathogens. Some may be transmitted with the allograft as donor-derived infections, while others result from exposure, either soon after the transplant or from more distant exposures when infection is latent and reactivates in the setting of immune suppression. Simultaneous infections with multiple viral or viral and nonviral pathogens are common. The risk for viral infection is a function of the intensity of exposure and virulence of the specific virus, the intensity of immune suppression used to prevent graft rejection or graft-versus-host disease, underlying immune deficits, and factors affecting host susceptibility. Studies of viral latency, reactivation, and of the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This article covers specific issues relating to viral infection in SOT and HSCT; additional details regarding these viral infections are also found elsewhere in this text.


title: Potential applications of plant biotechnology against SARS-CoV-2

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic (COVID-19). There is a massive international effort underway to develop diagnostic reagents, vaccines and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises in order to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here we look at some of the ways in which plants can and are being used in the fight against COVID-19.


title: Nonsense-Mediated mRNA Decay: Pathologies and the Potential for Novel Therapeutics

text: Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a surveillance pathway used by cells to control the quality mRNAs and to fine-tune transcript abundance. NMD plays an important role in cell cycle regulation, cell viability, DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism caused by genetic mutations or dys-regulation of the NMD pathway can lead to pathologies, including neurological disorders, immune diseases and cancers. The role of NMD in cancer development is complex, acting as both a promoter and a barrier to tumour progression. Cancer cells can exploit NMD for the downregulation of key tumour suppressor genes, or tumours adjust NMD activity to adapt to an aggressive immune microenvironment. The latter case might provide an avenue for therapeutic intervention as NMD inhibition has been shown to lead to the production of neoantigens that stimulate an immune system attack on tumours. For this reason, understanding the biology and co-option pathways of NMD is important for the development of novel therapeutic agents. Inhibitors, whose design can make use of the many structures available for NMD study, will play a crucial role in characterizing and providing diverse therapeutic options for this pathway in cancer and other diseases.


title: Canine Coronavirus: Not Only an Enteric Pathogen

text: This article reviews the currently available literature on pantropic canine coronavirus (CCoV), providing a meaningful update on the virologic, epidemiologic, clinical, diagnostic, and prophylactic aspects of the infections caused by this emerging pathogen of dogs. It also describes pantropic CCoV-induced disease reproduced under experimental conditions.


title: The human severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein is distinct from its counterpart in animal SARS-CoV and down-regulates the expression of the envelope protein in infected cells

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV), isolated from humans infected during the peak of epidemic, encodes two accessory proteins termed as 8a and 8b. Interestingly, the SARS-CoV isolated from animals contains an extra 29-nucleotide in this region such that these proteins are fused to become a single protein, 8ab. Here, we compared the cellular properties of the 8a, 8b and 8ab proteins by examining their cellular localizations and their abilities to interact with other SARS-CoV proteins. These results may suggest that the conformations of 8a and 8b are different from 8ab although nearly all the amino acids in 8a and 8b are found in 8ab. In addition, the expression of the structural protein, envelope (E), was down-regulated by 8b but not 8a or 8ab. Consequently, E was not detectable in SARS-CoV-infected cells that were expressing high levels of 8b. These findings suggest that 8b may modulate viral replication and/or pathogenesis.


title: Bronchial inflammation and the common cold: a comparison of atopic and non‐atopic individuals

text: Background Cold virus infections are associated with asthma attacks and with increased bronchial responsiveness even in normal subjects. Possible mechanisms include epithelial damage, interaction with adhesion molecules or with T‐helper cell subsets. Objective To determine whether colds increase lower airway inflammation, comparing atopic with non‐atopic normal subjects. Methods Thirty healthy volunteers (15 atopic) took part. Basehne tests included viral serology. microbiological culture and polymerase chain reaction for rhinovirus infection (HRV‐PCR), histamine bronchial provocation and bronchoscopy. Twenty subjects (eight atopic) underwent repeat tests when they developed a cold. Results Forced expiratory volume in one second (FEV(1)) was significantly lower during colds (‐0.19L [95% confidence mterval ‐0.10, ‐0.29], P= 0,0004) and there was a significant increase in bronchial responsiveness (+0.62 doublings of the dose‐response slope [+0.24, +1.00], P=0.003). Eight subjects (two atopic) had a diagnosed viral infection: two HRV. three coronavirus (HCV), one HRV + HCV, one parainfluenza III(PI) and one respiratory syncytial virus (RSV) (also Haemophilus influenzae). In biopsies, during colds, total eosinophils (EG1(+)) increased significantly (geometric mean 6.73‐fold [1.12,40.46], P=O.04). Activated eosinophils (EG2(+)) only increased significantly in the subgroup without diagnosed viral infection and particularly in atopic rhinitics. T‐suppressor (CD8(+)) cells also increased significantly (median +178.3 cells mm(2), P= 0.004). Epithelial expression of intercellular adhesion molecule‐1 (ICAM‐1) expression increased in four atopic rhinitics during colds. Bronchial washings showed a significant increase in neutrophils (GM 1.53‐fold [1.04,2.25], P= 0.02). Conclusion Lower airway inflammation was present in atopic and non‐atopic normal subjects with colds. Atopic subjects differed in that they were less likely to have positive virological tests and were more likely to show activated eosinophilia in the lower airway, despite a similar spectrum of symptoms.


title: Crystal structure of wild-type and mutant human Ap4A hydrolase

text: Abstract Ap4A hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17), an enzyme involved in a number of biological processes, is characterized as cleaving the polyphosphate chain at the fourth phosphate from the bound adenosine moiety. This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common αβα-sandwich architecture. Interestingly, two sulfate ions and one diphosphate coordinated with some conserved residues were observed in the active cleft, which affords a better understanding of a possible mode of substrate binding.


title: Sequential symptomatic analysis in probable severe acute respiratory syndrome cases()

text: STUDY OBJECTIVE: Previous reports on severe acute respiratory syndrome (SARS) described mainly its symptoms. However, the time sequence of symptom development was rarely discussed. The objective of this study is to chronologically document the time sequence of symptom development in probable SARS cases and compare that of the febrile non-SARS cases, thus providing valuable information for early recognition of the disease. METHODS: This prospective, descriptive, cohort study was conducted in an academic university hospital in Taipei, Taiwan, from March 14 through May 12, 2003. Patients presenting to the emergency department (ED) with a temperature of at least 38.0°C (≥100.3°F) and exposure history were evaluated with a structured protocol. Detailed time sequences of individual symptoms were recorded, and chest radiography and laboratory test results were obtained. Probable SARS cases were determined by the Center of Disease Control Taiwan. Children younger than 15 years and suspected SARS patients with negative polymerase chain reaction results were excluded from final analysis. RESULTS: Seventy-nine SARS and 220 non-SARS cases were analyzed. The major clinical symptoms of SARS patients on ED presentation were myalgia, loose stool or diarrhea, nonproductive cough or dyspnea, headache, and chills. Upper airway symptoms, including rhinorrhea and sore throat, were rarely seen in the SARS patients but were common in the non-SARS group. Characteristic symptom sequence, consisting of initial fever accompanied by diarrhea and myalgia and then progressive respiratory symptoms, was identified in 55 SARS patients (69.6%; 95% confidence interval [CI] 0.60 to 0.80) but only 7 (3.2%; 95% CI 0.008 to 0.05) non-SARS patients. Chest radiographic abnormality may precede lower respiratory tract symptoms in some SARS patients. CONCLUSION: During an outbreak period, recognition of possible SARS cases depends on the heightened awareness of its clinical presentation. Aside from travel and contact history, the time sequence of the accompanying symptoms of SARS should help first-line physicians screen SARS patients at an early stage.


title: Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China

text: Abstract The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 °C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 °C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.


title: Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development

text: Novel Coronavirus (nCoV) outbreak in the city of Wuhan, China during December 2019, has now spread to various countries across the globe triggering a heightened containment effort. This human pathogen is a member of betacoronavirus genus carrying 30 kilobase of single positive-sense RNA genome. Understanding the evolution, zoonotic transmission, and source of this novel virus would help accelerating containment and prevention efforts. The present study reported detailed analysis of 2019-nCoV genome evolution and potential candidate peptides for vaccine development. This nCoV genotype might have been evolved from a bat-CoV by accumulating non-synonymous mutations, indels, and recombination events. Structural proteins Spike (S), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein contains a 39 nucleotide (5’-aAT GGT GTT GAA GGT TTT AAT TGT TAC TTT CCT TTA CAA Tca-3’) sequence insertion, which shares homology to fish genomic sequence of Myripristis murdjan, an abundant fish type in Indo-Pacific Ocean. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region population. These immunodominant epitopes can be incorporated in universal subunit CoV vaccine. Diverse HLA types and variations in the epitope binding affinity may contribute to the wide range of immunopathological outcomes of circulating virus in humans. Our findings emphasize the requirement for continuous surveillance of CoV strains in live animal markets to better understand the viral adaptation to human host and to develop practical solutions to prevent the emergence of novel pathogenic CoV strains.


title: Evidence-based spectrum of antimicrobial activity for disinfection of bronchoscopes

text: Summary Processing of bronchoscopes after a physical examination has to eliminate all micro-organisms that could have contaminated the endoscope and that may harm the following patient. The aim of this analysis is to define those micro-organisms that may contaminate the bronchoscope during the examination and that may cause disease in other patients. Methods Research of literature and analysis of laboratory data. Results During the passage of the respiratory tract the bronchoscope will be contaminated by the physiological flora of oral cavity, nasopharynx, trachea, bronchi, and pulmonary tissues. Whilst the oral cavity, the nasopharynx and the pharynx are the habitat for a great variety of bacteria the lower respiratory tract is virtually free of micro-organisms. However, in ventilated patients trachea and bronchi can become colonized as the result of bypassing the cleansing effect of the ciliated epithelium. In addition all agents that can cause bronchitis or pneumonia in immunocompromised or otherwise healthy individuals are potential contaminants of bronchoscopes. These microorganisms include bacteria, mycobacteria, yeasts and moulds, enveloped and non-enveloped viruses and rarely parasites. The bronchoscopic procedure can result in epithelial injury with subsequent bleeding. Therefore, all blood-borne pathogens, e.g. HIV or HBV are also potential contaminants of the bronchoscope. There are several reports of transmission of micro-organisms due to incomplete or faulty cleaning and disinfection procedures of bronchoscopes. These incidents include nearly all classes of micro-organisms but not parasites or viruses. However, the incubation period of viruses can be long and the association between bronchoscopy and infection may be obscure. Endospore forming micro-organisms and parasites are not part of the normal flora of the respiratory tract and may rarely cause disease, usually only in severely immunocompromised patients, but transmission of such organisms by bronchoscopy has never been reported. Conclusion The antimicrobial activity of the disinfection process, including chemical disinfectants for endoscopes has to include bacteria, fungi and viruses. Sporicidal activity may be only warranted in specific patient populations, i.e. after bronchoscopy of suspected anthrax patients or before examination of severely immunocompromised patients.


title: The Common Missed Handwashing Instances and Areas after 15 Years of Hand-Hygiene Education

text: The outbreak of severe acute respiratory syndrome (SARS) claimed the lives of 286 Hong Kong people in 2003. Since then, the Hong Kong government has been promoting the benefits of proper hand hygiene. There are few studies that explore the general quality of handwashing and the hand-hygiene practices of the public of Hong Kong; given this, the aim of this study is to explore this neglected topic. This study is a quantitative study that was conducted in January 2018. The results show that the majority of participants only wash their hands after using the toilet (87%) or handling vomitus or faecal matter (91%). The mean duration of handwashing was 36.54 seconds (SD = 18.57). The areas of the hand most neglected during handwashing were the fingertips (48.1%), medial area (30.5%), and back of the hand (28%). A multiple logistic regression shows that participants who have reached third-level education or higher often tend to be more hand hygienic than those who have not reached third-level education (p ≤ 0.001, B = 1.003). Thus, participants aged 30 and above tend to neglect 5 more areas of the hand than those aged below 30 (p=0.001, B = 4.933).


title: Delivering risk information in a dynamic information environment: Framing and authoritative voice in Centers for Disease Control (CDC) and primetime broadcast news media communications during the 2014 Ebola outbreak

text: Abstract Objective During a disease outbreak, media serve as primary transmitters of information from public health agencies to the public, and have been shown to influence both behavior and perception of risk. Differences in news frequency, framing and information source can impact the public's interpretation of risk messages and subsequent attitudes and behaviors about a particular threat. The media's framing of an outbreak is important, as it may affect both perception of risk and the ability to process important health information. Methods To understand how risk communication by the Centers for Disease Control and Prevention (CDC) during the 2014 Ebola outbreak was framed and delivered and to what extent primetime broadcast news media mirrored CDC's framing and authoritative voice, 209 CDC communications and primetime broadcast transcripts issued between July 24 and December 29, 2014 were analyzed and coded by thematic frame and authoritative voice. Dominant frame and voice were determined for each month and for overall period of analysis. Results Medical frame was dominant in CDC (60%), Anderson Cooper 360 (49%), The Rachel Maddow Show (47%) and All In with Chris Hayes (47%). The human interest frame was dominant in The Kelly File (45%), while The O'Reilly Factor coverage was equally split between sociopolitical and medical frames (28%, respectively). Primetime news media also changed dominant frames over time. Dominant authoritative voice in CDC communications was that of CDC officials, while primetime news dominantly featured local and federal (non-CDC) government officials and academic/medical experts. Conclusion Differences in framing and delivery could have led the public to interpret risk in a different way than intended by CDC. Overall, public health agencies should consider adapting risk communication strategies to account for a dynamic news environment and the media's agenda. Options include adapting communications to short-form styles and embracing the concept of storytelling.


title: Effectively Communicating Climate Science beyond Academia: Harnessing the Heterogeneity of Climate Knowledge

text: Approaches to communicating climate science beyond academia are necessary for enhancing salience, understanding, and engagement and accelerating action. This Primer discusses the heterogeneous manner in which climate change messaging is received by different audiences, how social scientific approaches could help to better tailor climate change messaging to this varied landscape, and how attempts to close this gap must consider the emotional and affective dimensions of climate messaging. We explore how the use of narratives can enhance effective climate science communication and emphasize the importance of evidence-based advocacy in the current era of global challenges, uncertainty, and post-truth.


title: Development of a molecular-beacon-based multi-allelic real-time RT-PCR assay for the detection of human coronavirus causing severe acute respiratory syndrome (SARS-CoV): a general methodology for detecting rapidly mutating viruses

text: Emerging infectious diseases have caused a global effort for development of fast and accurate detection techniques. The rapidly mutating nature of viruses presents a major difficulty, highlighting the need for specific detection of genetically diverse strains. One such infectious agent is SARS-associated coronavirus (SARS-CoV), which emerged in 2003. This study aimed to develop a real-time RT-PCR detection assay specific for SARS-CoV, taking into account its intrinsic polymorphic nature due to genetic drift and recombination and the possibility of continuous and multiple introductions of genetically non-identical strains into the human population, by using mismatch-tolerant molecular beacons designed to specifically detect the SARS-CoV S, E, M and N genes. These were applied in simple, reproducible duplex and multiplex real-time PCR assays on 25 post-mortem samples and constructed RNA controls, and they demonstrated high target detection ability and specificity. This assay can readily be adapted for detection of other emerging and rapidly mutating pathogens.


title: Simultaneous detection of respiratory syncytial virus and human metapneumovirus by one-step multiplex real-time RT-PCR in patients with respiratory symptoms

text: BACKGROUND: Both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important viral pathogens causing respiratory tract infection (RTI) in the pediatric population. However, the clinical manifestations of RSV and hMPV infections are similar. Therefore, a reliable and rapid diagnostic tool is needed for diagnostic performance. METHODS: In order to optimize diagnosis efficiency of RTI, the aim of this study is to establish a rapid and advanced method for simultaneous detecting RSV and hMPV in nasopharyngeal aspirates specimens from patients. We designed a one-step triplex real-time RT-PCR (qRT-PCR) protocol using TaqMan probes for detecting RSV and hMPV. The plasmid clones containing RSV nucleoprotein gene and hMPV fusion gene were established as reference standards. We used virus culture supernatants from 86 known pediatric RTI patient to test the specificity and sensitivity of our assay. Then we used total 222 nasopharyngeal aspirates specimens from pediatric patients hospitalized with respiratory symptoms to evaluate our assay. RESULTS: Our one-step triplex qRT-PCR assay showed 100% sensitivity and specificity in testing RSV and hMPV in 86 known virus culture supernatants, with excellent linearity (R(2) > 0.99) and reliable reproducibility (CV lower than 1.04%). This assay has a wide dynamic range 10(2)-10(9)copies/reaction (limit of detection; LOD = 100 copies/reaction). A total of 222 patients hospitalized with respiratory symptoms were enrolled for clinical evaluation. In these samples, our qRT-PCR assay detected 68 RSV positive and 18 hMPV positive cases. However, standard virus culture only detected 8 RSV positive cases and 0 hMPV cases. Based on this improved triplex qRT-PCR assay, we found that RSV infection was associated with severe inflammation by chest X-ray and occurrence of pneumonia which were not observed previously. CONCLUSIONS: In summary, we have developed a highly specific and sensitive one-step triplex qRT-PCR assay to detect hMPV and RSV simultaneously. This assay offers a valuable tool for routine diagnosis.


title: Amelioration of COVID‐19 related cytokine storm syndrome: Parallels to chimeric antigen receptor‐T cell cytokine release syndrome

text: Coronavirus disease‐2019 (COVID‐19) severity appears to parallel the host immune response, with a subset of patients developing COVID‐19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID‐19,(2–5) and interleukin (IL)‐6 appears to play a central role in COVID‐19 related CSS.(6–8) Based on the success of IL‐6 receptor blockade for chimeric antigen receptor T‐cell therapy associated cytokine release syndrome (CAR T‐cell CRS), similar strategies using tocilizumab are being investigated in COVID‐19.


title: An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger

text: Recently developed vaccines provide a new way of controlling rotavirus in sub-Saharan Africa. Models for the transmission dynamics of rotavirus are critical both for estimating current burden from imperfect surveillance and for assessing potential effects of vaccine intervention strategies. We examine rotavirus infection in the Maradi area in southern Niger using hospital surveillance data provided by Epicentre collected over two years. Additionally, a cluster survey of households in the region allows us to estimate the proportion of children with diarrhea who consulted at a health structure. Model fit and future projections are necessarily particular to a given model; thus, where there are competing models for the underlying epidemiology an ensemble approach can account for that uncertainty. We compare our results across several variants of Susceptible-Infectious-Recovered (SIR) compartmental models to quantify the impact of modeling assumptions on our estimates. Model-specific parameters are estimated by Bayesian inference using Markov chain Monte Carlo. We then use Bayesian model averaging to generate ensemble estimates of the current dynamics, including estimates of [Formula: see text] , the burden of infection in the region, as well as the impact of vaccination on both the short-term dynamics and the long-term reduction of rotavirus incidence under varying levels of coverage. The ensemble of models predicts that the current burden of severe rotavirus disease is 2.6–3.7% of the population each year and that a 2-dose vaccine schedule achieving 70% coverage could reduce burden by 39–42%.


title: Free-roaming dogs limit habitat use of giant pandas in nature reserves

text: Giant pandas (Ailuropoda melanoleuca) were historically hunted using dogs and are currently threatened by free-roaming dogs and their associated diseases. To better understand the spatial magnitude of this threat, we used a GIS approach to investigate edge effects of dogs on giant panda habitat. We first examined two nature reserves with contrasting free-roaming dog populations: Liziping, with many dogs (~0.44/km(2)), and Daxiangling, with few dogs (~0.14/km(2)). Spatial analysis indicated that giant pandas at Liziping (but not Daxiangling) showed a shift in habitat use away from populated areas consistent with a risk response to the foray distance of free-roaming dogs (10.9 km path-distance). Most giant panda locations (86%) from the 2014 census in Liziping were clustered around remote “dog-free zones.” Expanding this analysis across the entire giant panda range revealed that 40% of panda habitat is within the foray distance of dogs. Our assessment will inform dog control programs including monitoring, education, veterinary care, and other measures. We recommend that reserves designated for the release of translocated pandas receive priority consideration for dog control efforts. Only by understanding and managing complex interactions between humans, domestic animals, and wild animals can we sustain natural systems in a world increasingly dominated by humans.


title: Poxviruses in Bats … so What?

text: Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.


title: Lutte contre la pandémie de maladie à coronavirus (Covid-19): tirer les leçons de la réponse à la maladie du virus Ebola

text: Abstract Coronavirus disease (COVID-19) is caused by a beta-coronavirus (SARS-CoV-2) that affects the lower respiratory tract and appears as pneumonia in humans. COVID-19 became apparent in December 2019 in Wuhan City of China, and has propagated profusely globally. Despite stringent global quarantine and containment drives, the incidence of COVID-19 keeps soaring high. Measures to minimize human-to-human transmission have been implemented to control the pandemic. However, special efforts to reduce transmission via efficient public health communications and dissemination of risks should be applied in susceptible populations including children, health care providers, and the elderly. In response to this global pandemic, this article summarizes proven strategies that could be employed to combat the COVID-19 disease outbreak, taking a cue from lessons learned from the Ebola virus disease response. Résumé La maladie à coronavirus (COVID-19) est causée par un bêta-coronavirus (SARS-CoV-2) qui affecte les voies respiratoires inférieures et se présente sous forme de pneumonie chez l'homme. La COVID-19 est apparue en décembre 2019 dans la ville chinoise de Wuhan, et s'est propagée à grande échelle dans le monde entier. Malgré des mesures de quarantaine et de confinement rigoureuses, l'incidence de COVID-19 continue de grimper en flèche. Des mesures visant à minimiser la transmission interhumaine ont été mises en œuvre pour contrôler la pandémie. Toutefois, des efforts particuliers pour réduire la transmission par le biais de communications efficaces en matière de santé publique et de diffusion des risques doivent être déployés dans les populations sensibles, notamment les enfants, les prestataires de soins de santé et les personnes âgées. En réponse à cette pandémie mondiale, cet article résume les stratégies éprouvées qui pourraient être employées pour combattre l'épidémie de maladie COVID-19, en s'inspirant des leçons tirées de la réponse à la maladie du virus Ebola.


Adenovirus sneak attacks during the H7N9 flu season


title: Together we unite: the role of the Commonwealth in achieving universal health coverage through pharmaceutical care amidst the COVID-19 pandemic

text: The world currently faces unprecedented health challenges as COVID-19 poses a huge threat to health systems, economies and societies as we know it. The events of the current COVID-19 pandemic have further emphasised existing issues within our health systems. There is no better time than now to come together in global solidarity to tackle these evolving threats of COVID-19 pandemic. The Commonwealth is an ideally placed network to tackle these global health challenges, with its wide-reaching networks of governmental, non-governmental and civil society organisations across all continents. Although the biennial Commonwealth Heads of Government Meeting (CHOGM) originally scheduled to take place in Kigali in Rwanda 22–27 June 2020 has been postponed in view of COVID-19, Commonwealth country discussions are continuing, centred on the CHOGM key theme of ‘Delivering a Common Future: Connecting, Innovating, Transforming’, and five subthemes of Information and Communications Technology (ICT) and Innovation; Trade; Environment; Governance and the Rule of Law; and Youth. The planned CHOGM and Commonwealth itself provides all members a timely platform to consider innovative ways to connect, innovate and transform healthcare to meet the needs of their populations. This commentary considers these five CHOGM subthemes and how member nations can be supported to achieve universal health coverage through optimising medicines use and outcomes, in the midst of a global pandemic in line with the global health agenda.


Acute respiratory disease surveillance – Comparison of the two different seasons in the Czech Republic


title: Feasibility study for the use of self‐collected nasal swabs to identify pathogens among participants of a population‐based surveillance system for acute respiratory infections (GrippeWeb‐Plus)—Germany, 2016

text: BACKGROUND: Internet‐based participatory surveillance systems, such as the German GrippeWeb, monitor the frequency of acute respiratory illnesses on population level. In order to interpret syndromic information better, we devised a microbiological feasibility study (GrippeWeb‐Plus) to test whether self‐collection of anterior nasal swabs is operationally possible, acceptable for participants and can yield valid data. METHODS: We recruited 103 GrippeWeb participants (73 adults and 30 children) and provided them with a kit, instructions and a questionnaire for each sample. In the first half of 2016, participants took an anterior nasal swab and sent it to the Robert Koch Institute whenever an acute respiratory illness occurred. Reporting of illnesses through the GrippeWeb platform continued as usual. We analysed swabs for the presence of human c‐myc‐DNA and 22 viral and bacterial pathogens. After the study, we sent participants an evaluation questionnaire. We analysed timeliness, completeness, acceptability and validity. RESULTS: One hundred and two participants submitted 225 analysable swabs. Ninety per cent of swabs were taken within 3 days of symptom onset. Eighty‐nine per cent of swabs had a corresponding reported illness in the GrippeWeb system. Ninety‐nine per cent of adults and 96% of children would be willing to participate in a self‐swabbing scheme for a longer period. All swabs contained c‐myc‐DNA. In 119 swabs, we identified any of 14 viruses but no bacteria. The positivity rate of influenza was similar to that in the German physician sentinel. CONCLUSION: Self‐collection of anterior nasal swabs proofed to be feasible, was well accepted by participants, gave valid results and was an informative adjunct to syndromic data.


title: Virus et sensibilisation

text: Résumé Les virus respiratoires peuvent, en se répliquant aussi bien au niveau de l’épithélium respiratoire supérieur qu’inférieur, induire des sifflements. La plupart des études cliniques soulignent qu’une symptomatologie sifflante secondaire à l’atteinte par un virus respiratoire durant la prime enfance est liée à un risque ultérieur d’asthme. Les virus peuvent induire une exacerbation asthmatique par un effet direct sur sa cible principale, l’épithélium, mais aussi d’une réaction immuno-inflammatoire médiée par voie systémique. Par ailleurs, des études ont également montré des résultats discordants dans la capacité d’une infection virale d’induire des réponses allergiques significatives. Est-ce le virus l’initiateur de l’asthme allergique ou les sifflements viro-induits le révélateur d’enfants déjà prédisposés à l’atopie en raison d’anomalies préexistantes pulmonaires et/ou de la réponse immunitaire ? Abstract Respiratory viruses are able to replicate in both the upper and lower respiratory epithelium, thus inducing wheezing. Most clinical studies suggest that wheezing illnesses due to respiratory viruses in early childhood are linked to a risk for asthma. Viruses may induce asthma exacerbations through direct effects on their main target, the respiratory epithelium, as well as via a systemic immune-inflammatory reaction. On other hand, studies have also yielded conflicting results in regard to the ability of viral infection to enhance subsequent allergic responses. Do early viral illnesses cause allergic asthma or viral wheezing episodes serve to reveal children who are already predisposed to this disease on basis of an abnormal lung physiology and/or immune response?


title: Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response

text: Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea in human and animal. In piglets, ETEC having F4 fimbriae (F4(+) ETEC) induce severe diarrhea, dependent on the presence of receptors for F4 (F4R). In this study, porcine aminopeptidase N (pAPN) was identified as an F4R by comparative proteomic analysis of brush border proteins of F4R(+) and F4R(−) pigs and by adherence/internalization experiments on pAPN-transfected cells. Binding of F4 fimbriae to pAPN depended on sialic acid containing carbohydrate moieties, and resulted in clathrin-mediated endocytosis of the fimbriae. Endocytosis via pAPN was not restricted to F4 fimbriae, but was also observed for anti-pAPN antibodies. Both F4 fimbriae- and pAPN-specific antibodies were taken up in vivo by porcine enterocytes and induced subsequently a rapid immunoglobulin A and G response. In conclusion, we identified pAPN as an endocytotic receptor for F4 fimbriae and highlight the opportunity to target vaccine antigens to this epithelial receptor. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2012.37) contains supplementary material, which is available to authorized users.


title: Novel Coronavirus (COVID-19): Violence, Reproductive Rights and Related Health Risks for Women, Opportunities for Practice Innovation

text: While the novel coronavirus (COVID-19) has broad health implications across the globe, being overlooked in response and policy debates is the impact on women’s reproductive rights and violence risk. This is especially salient for minoritized women. In this commentary, we describe the potential negative impact of mandates such as shelter-in-place for domestic violence victims, and how public reproductive health policy is being shaped to disadvantage women, especially minoritized women. We argue that now is the time for violence prevention leaders to advocate for bold action. This includes prioritizing the needs of women (especially minoritized women) in medical, social and legal settings using innovative intervention and service engagement (e.g., e-filing for protection orders, virtual advocacy services), urging policy makers to pass legislation to support women, and shining an accountability spotlight on leadership.


title: Unraveling virus identity by detection of depleted probes with capillary electrophoresis

text: Abstract With the emergence of new viral infections and pandemics, there is a need to develop faster methods to unravel the virus identities in a large number of clinical samples. This report describes a virus identification method featuring high throughput, high resolution, and high sensitivity detection of viruses. Identification of virus is based on liquid hybridization of different lengths of virus-specific probes to their corresponding viruses. The probes bound to target sequences are removed by a biotin–streptavidin pull-down mechanism and the supernatant is analyzed by capillary electrophoresis. The probes depleted from the sample appear as diminished peaks in the electropherograms and the remaining probes serve as calibrators to align peaks in different capillaries. The virus identities are unraveled by a signal processing and peak detection algorithm developed in-house. Nine viruses were used in the study to demonstrate how the system works to unravel the virus identity in single and double virus infections. With properly designed probes, the system is able to distinguish closely related viruses. The system takes advantage of the high resolution feature of capillary electrophoresis to resolve probes that differ by length. The method may facilitate virus identity screen from more candidate viruses with an automated 4-color DNA sequencer.


title: The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family

text: Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus–A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2(−∆∆Ct) method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID(50)/ml (tissue culture infectious dose that will produce cytopathic effect in 50 % of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11033-014-3019-7) contains supplementary material, which is available to authorized users.


SARS-CoV2 in the peritoneal waste in a patient treated with peritoneal dialysis