title: Glucose signalling pathway controls the programmed ribosomal frameshift efficiency in retroviral‐like element Ty3 in Saccharomyces cerevisiae

text: Ty3 elements of S. cerevisiae contain two overlapping coding regions, GAG3 and POL3, which are functional homologues of retroviral gag and pol genes, respectively. Pol3 is translated as a Gag3‐Pol3 fusion protein dependent on a +1 programmed frameshift at a site with the overlap between the two genes. We show that the Ty3 frameshift frequency varies up to 10‐fold in S. cerevisiae cells depending on carbon source. Frameshift efficiency is significantly lower in cells growing on glucose as carbon source than in cells growing on poor alternative carbon sources (glycerol/lactate or galactose). Our results indicate that Ty3 programmed ribosomal frameshift efficiency in response to glucose signalling requires two protein kinases: Snf1p and cAMP‐dependent protein kinase A (PKA). Increased frameshifting on alternative carbon sources also appears to require cytoplasmic localization of Snf1p, mediated by the Sip2p protein. In addition to the two required protein kinases, our results implicate that Stm1p, a ribosome‐associated protein involved in nutrient sensing, is essential for the carbon source‐dependent regulation of Ty3 frameshifting. These data indicate that Ty3 programmed ribosomal frameshift is not a constitutive process but that it is regulated in response to the glucose‐signalling pathway. Copyright © 2011 John Wiley & Sons, Ltd.


title: Self-assembled natural rubber/silica nanocomposites: Its preparation and characterization

text: Abstract A novel natural rubber/silica (NR/SiO2) nanocomposite is developed by combining self-assembly and latex-compounding techniques. The results show that the SiO2 nanoparticles are homogenously distributed throughout NR matrix as nano-clusters with an average size ranged from 60 to 150nm when the SiO2 loading is less than 6.5wt%. At low SiO2 contents (⩽4.0wt%), the NR latex (NRL) and SiO2 particles are assembled as a core-shell structure by employing poly (diallyldimethylammonium chloride) (PDDA) as an inter-medium, and only primary aggregations of SiO2 are observed. When more SiO2 is loaded, secondary aggregations of SiO2 nanoparticles are gradually generated, and the size of SiO2 cluster dramatically increases. The thermal/thermooxidative resistance and mechanical properties of NR/SiO2 nanocomposites are compared to the NR host. The nanocomposites, particularly when the SiO2 nanoparticles are uniformly dispersed, possess significantly enhanced thermal resistance and mechanical properties, which are strongly depended on the morphology of nanocomposites. The NR/SiO2 has great potential to manufacture medical protective products with high performances.


title: Mouse Hepatitis Virus Infection Upregulates Genes Involved in Innate Immune Responses

text: Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, the time of peak inflammation, reveals robust expression of IFN-γ, IL-12 and mKC. Data suggest that activated microglia and inflammatory mediators contribute to a local CNS microenvironment that regulates viral replication and IFN-γ production during the acute phase of infection, which in turn can cause phagolysosome maturation and phagocytosis of the myelin sheath, leading to demyelination.


President’s Page: The Impact of the COVID-19 Pandemic on Cardiac CT


title: Get an exact diagnosis in hours

text: A device that can identify all bacteria, viruses and fungi known to cause disease in humans should make diagnosis less of a guessing game, helping to curb the problem of antibiotic resistance


title: The porcine virome and xenotransplantation

text: The composition of the porcine virome includes viruses that infect pig cells, ancient virus-derived elements including endogenous retroviruses inserted in the pig chromosomes, and bacteriophages that infect a broad array of bacteria that inhabit pigs. Viruses infecting pigs, among them viruses also infecting human cells, as well as porcine endogenous retroviruses (PERVs) are of importance when evaluating the virus safety of xenotransplantation. Bacteriophages associated with bacteria mainly in the gut are not relevant in this context. Xenotransplantation using pig cells, tissues or organs is under development in order to alleviate the shortage of human transplants. Here for the first time published data describing the viromes in different pigs and their relevance for the virus safety of xenotransplantation is analysed. In conclusion, the analysis of the porcine virome has resulted in numerous new viruses being described, although their impact on xenotransplantation is unclear. Most importantly, viruses with known or suspected zoonotic potential were often not detected by next generation sequencing, but were revealed by more sensitive methods.


Marked escalation in journal submissions during COVID19 pandemic


title: Including the public in pandemic planning: a deliberative approach

text: BACKGROUND: Against a background of pandemic threat posed by SARS and avian H5N1 influenza, this study used deliberative forums to elucidate informed community perspectives on aspects of pandemic planning. METHODS: Two deliberative forums were carried out with members of the South Australian community. The forums were supported by a qualitative study with adults and youths, systematic reviews of the literature and the involvement of an extended group of academic experts and policy makers. The forum discussions were recorded with simultaneous transcription and analysed thematically. RESULTS: Participants allocated scarce resources of antiviral drugs and pandemic vaccine based on a desire to preserve society function in a time of crisis. Participants were divided on the acceptability of social distancing and quarantine measures. However, should such measures be adopted, they thought that reasonable financial, household and psychological support was essential. In addition, provided such support was present, the participants, in general, were willing to impose strict sanctions on those who violated quarantine and social distancing measures. CONCLUSIONS: The recommendations from the forums suggest that the implementation of pandemic plans in a severe pandemic will be challenging, but not impossible. Implementation may be more successful if the public is engaged in pandemic planning before a pandemic, effective communication of key points is practiced before and during a pandemic and if judicious use is made of supportive measures to assist those in quarantine or affected by social isolation measures.


title: The limits of global health diplomacy: Taiwan’s observer status at the world health assembly

text: In 2009, health authorities from Taiwan (under the name “Chinese Taipei”)(a) formally attended the 62(nd) World Health Assembly (WHA) of the World Health Organization as observers, marking the country’s participation for the first time since 1972. The long process of negotiating this breakthrough has been cited as an example of successful global health diplomacy. This paper analyses this negotiation process, drawing on government documents, formal representations from both sides of the Taiwan Strait, and key informant interviews. The actors and their motivations, along with the forums, practices and outcomes of the negotiation process, are detailed. While it is argued that non-traditional diplomatic action was important in establishing the case for Taiwan’s inclusion at the WHA, traditional concerns regarding Taiwanese sovereignty and diplomatic representation ultimately played a decisive role. The persistent influence of these traditional diplomatic questions illustrates the limits of global health diplomacy.


title: Rabbit Clinical Pathology

text: Abstract With rabbit patients, as in other species, analyzing blood and urine samples can be useful and informative, although interpretation of the results is sometimes challenging. This article summarizes the interpretation of laboratory results from rabbits. Hematological parameters can yield information about the red blood cell population and leukocyte response to stress and pathogens. Biochemistry evaluation can be used to investigate liver, kidney, and other organ function, and urinalysis results may yield additional information about kidney function and electrolyte imbalances. Serological tests are available for several pathogens of rabbits, including Encephalitozoon cuniculi, although the significance of positive results and antibody titers is not clear. Serum protein electrophoresis aids the understanding of protein disorders and the immune response to acute and chronic inflammation.


title: Randomized, double‐blind, placebo‐controlled trial of interferon Alfa2a with and without amantadine as initial treatment for chronic hepatitis C

text: Although the antiviral effects of amantadine sulphate (1‐aminoadamantan sulphate) have not been characterized for the hepatitis C virus (HCV), previous pilot studies have suggested promising results in patients with chronic hepatitis C. The aim of the present study was to compare the efficacy, safety, and health‐related quality of life (HRQOL) of interferon alfa (IFN‐α) alone or in combination with oral amantadine for treatment of chronic hepatitis C. One hundred nineteen previously untreated patients with chronic hepatitis C were randomly allocated to treatment with IFN‐α2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks, followed by 3 megaunits thrice weekly for an additional 24 weeks plus amantadine sulphate administered orally 100 mg twice a day for 48 weeks or the same IFN regimen plus a matched placebo. The primary endpoint was undectable serum HCV RNA (<1,000 copies/mL) at week 24 after treatment. At the end of treatment and the 24‐week follow‐up period serum HCV RNA was undetectable in 20 (34%) and 6 (10%) of the 59 patients treated with the combination IFN‐α plus amantadine and in 20 (33%) and 13 (22%) of the 60 patients treated with IFN‐α alone, respectively (P = n.s.). Discontinuation of therapy for adverse events was similar in both treatment groups. Although treatment with IFN‐α worsened HRQOL, combination with amantadine showed a substantial trend to improve fatigue and vigor. In conclusion, combination therapy IFN‐α plus amantadine is as effective as IFN‐α monotherapy in previously untreated patients with chronic hepatitis C.


title: Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%– 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere.


Airway permeability


title: The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak

text: Motivated by the rapid spread of COVID-19 in Mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated based on internationally reported cases, and shows that at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in Mainland China, but has a more marked effect at the international scale, where case importations were reduced by nearly 80% until mid February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.


title: Preparations for the Safe Management of Severe Acute Respiratory Syndrome (SARS) Research Protocol Patients

text: Abstract ISSUE: The Warren G Magnuson Clinical Center (CC) strives to achieve a balance between its mission and worker and patient safety. PROJECT: As part of its mission as one of the government's primary research facilities, the CC must be able to address epidemiologically significant public health concerns as they arise. After its initial description in the fall of 2002, the global threat of SARS became readily apparent. To address its mission, investigators working at the CC designed two protocols to study this new disease. To protect our patients and our staff, we quickly developed infection control guidelines based on what was known about the epidemiology and pathogenesis of this new disease. RESULTS: We created a multidisciplinary team to identify risk points during the admission and treatment phases of these protocols. This group met once or twice weekly for 6 months. New policies and procedures were created which were patterned after the CDC guidelines but which met the unique needs of our existing infrastructure and patient populations. We created a new position (isolation monitor) to ensure compliance with infection control precautions. We also conducted a failure mode and effects analysis (FMEA) to identify additional areas of risk. Policies and procedures were reviewed by: 1) a multi-institute physician committee, 2) an external expert in hospital epidemiology, and 3) the CC Medical Executive Committee. Detailed practice sessions have been held to ensure compliance with these new and detailed precautions. LESSONS LEARNED: Readiness for complex infectious diseases is multifaceted and requires advance planning and detailed assessments. Preparing for SARS has placed our organization in a much better position to deal with emerging airborne infectious diseases.


title: Increased ACE2 Expression in the Bronchial Epithelium of COPD Patients who are Overweight

text: OBJECTIVE: Mortality from coronavirus disease 2019 (COVID‐19) is increased in COPD patients. Furthermore, higher body mass index (BMI) is related to severe disease. SARS‐CoV‐2 utilises angiotensin converting enzyme 2 (ACE2) to gain cellular entry. METHODS: We have investigated whether ACE2 bronchial epithelial expression is increased in COPD patients who are overweight compared to those who are not by RNA sequencing. RESULTS: We observed increased ACE2 expression in COPD patients who are overweight (mean BMI 29 kg/m(2)) compared to those notoverweight (mean BMI 21 kg/m(2)) (p=0.004). CONCLUSION: Increased ACE2 expression may cause increased SARS‐CoV‐2 infection of the respiratory tract. COPD patients who are overweight may be at greater risk of developing severe COVID‐19.


title: Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Infection in Camel Workers in Qatar During 2013–2014: A Case-Control Study

text: The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibodies and 43 workers without antibodies were included. Some camel-related activities may pose a higher risk of MERS-CoV infection, as may cross-border movements of camels, poor hand hygiene, and overnight hospital stays with respiratory complaints. The risk factors identified in this study can be used to develop infection prevention and control measures for human MERS-CoV infections.


title: Application of refined management in prevention and control of the coronavirus disease 2019 epidemic in non-isolated areas of a general hospital

text: Abstract Objective This article summarizes the experience in the prevention and control of coronavirus disease 2019(COVID-19) epidemic in non-isolated areas in a general hospital. Methods Based on refined management theory, we professionally developed the standards for prevention and control of COVID-19 in non-isolated areas, systematically implemented various prevention and control measures, performed gridding audits, effectively communicated among teams and between medical staff and patients assisted by information techniques, and reported results for quality improvement. Results There was no hospital-acquired COVID-19 infections among staff in the hospital. The rates of mask-wearing, epidemiological history screening, and the medical supplies disinfection were all 100% in the hospital. The accuracy rate of mask-wearing of patients and their families was 73.79% and the compliance rate of their hand hygiene was 40.78%. Conclusion Refined management strategies for the prevention and control of COVID-19 infection in non-isolated areas of the general hospital are effective. The accuracy rate of mask-wearing and hand hygiene compliance of patients and their families need to be further improved.


title: Development of HPV(16,18,31,45) E5 and E7 peptides-based vaccines predicted by immunoinformatics tools

text: OBJECTIVES: Viral oncoproteins are ideal targets in therapeutic vaccines for functional inhibition of human papillomaviruses (HPVs). Herein, we designed the peptide constructs derived from E5 and E7 oncoproteins of high-risk HPV types 16, 18, 31 and 45 using the bioinformatics tools and investigated their potency in mice. RESULTS: The framework of the combined in silico/in vivo analysis included (1) to determine physicochemical properties of the designed constructs, (2) to identify potential IFN-γ-inducing epitopes, (3) to assess allergenicity, (4) to recognize linear and discontinuous B cell epitopes using modeling and validation of 3D structure of the designed constructs, and (5) to evaluate immune responses and tumor growth in vivo. Our in silico data determined high potency of the HPV(16,18,31,45) E5 and HPV(16,18,31,45) E7 peptides for trigger B- and T-cell responses, and IFN-γ secretion. In vivo study indicated that the mixture of E5 and E7 immunodominant peptides from four types of high-risk HPV could induce Th1 immune response, and protect completely mice against TC-1 tumor cells. CONCLUSION: Generally, the combined in silico/in vivo approaches showed the ability of the designed E5 and E7 peptide constructs from four major high-risk HPV types for development of therapeutic vaccines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10529-020-02792-6) contains supplementary material, which is available to authorized users.


title: How can we evaluate an interrelation of symptoms?

text: A pandemic of 2019 novel coronavirus (COVID-19) is an international problem and factors associated with increased risk of mortality have been reported. However, there exists limited statistical method to estimate a comprehensive risk for a case in which a patient has several characteristics and symptoms concurrently. We applied Boolean Monte Carlo method (BMCM) to the Novel Corona Virus 2019 Dataset to determine interrelation of patient's characteristics and symptoms. In the analyses, age, fever as an onset symptom, and sex were used as explanatory variables, and death as the objective variable. Among 265 patients included in the analysis, the interrelations for estimating death were determined as age "and" fever "and" sex (p < 0.0001 for both operators). This result indicates that satisfying the three conditions of age, fever, and sex concurrently may be associated with an increased risk of mortality.


title: Research on the urban resilience evaluation with hybrid multiple attribute TOPSIS method: an example in China

text: Cities are important barriers to protect people’s lives and property in the face of natural disasters, economic fluctuations and epidemic diseases. The evaluation of urban resilience is a hybrid multiple attribute group decision-making problem involving both crisp and fuzzy indicators. In order to evaluate the urban resilience reasonably and quantitatively, an urban resilience evaluation index system is established, including four primary indicators of ecological environment, municipal facilities, economic development and social development, and 28 secondary indicators. An evaluation model based on the theory of intuitionistic fuzzy set and TOPSIS method is proposed. The intuitionistic trapezoidal fuzzy number is used to quantify the fuzzy index and determine the weights of experts. The weight of each index is determined based on the maximizing deviation method. The relevant data of Dalian City from 2013 to 2017 are collected to evaluate the city resilience, and a sensitivity analysis is carried out based on the proposed model. The results may provide insights for the further urban resilience promotion.


title: Human rhinovirus infections of the lower respiratory tract in hematopoietic stem cell transplant recipients

text: BACKGROUND: Human rhinoviruses (HRVs) are a common cause of upper respiratory infection (URI) in hematopoietic stem cell transplant (HSCT) recipients; yet, their role in lower respiratory illness is not well understood. METHODS: We performed a retrospective chart review of HSCT recipients with HRV infection from the time molecular detection methods were implemented at our institution in 2008. Factors associated with proven or possible HRV pneumonia at the first HRV detection were evaluated by univariate and multivariate analysis. We then characterized all episodes of proven and possible HRV pneumonia from the initial HRV infection through a 1-year follow-up period. RESULTS: Between 2008 and 2011, 63 HSCT recipients had ≥ 1 documented HRV infections. At first HRV detection, 36 (57%) patients had HRV URI and 27 (43%) had proven or possible HRV pneumonia; in multivariate analysis, hypoalbuminemia (odds ratio [OR] 9.5, 95% confidence interval [CI] 1.3–71.7; P=0.03) and isolation of respiratory co-pathogen(s) (OR 24.2, 95%CI 2.0–288.4; P=0.01) were independently associated with pneumonia. During the study period, 22 patients had 25 episodes of proven HRV pneumonia. Fever (60%), cough (92%), sputum production (61%), and dyspnea (60%) were common symptoms. Fifteen (60%) episodes demonstrated bacterial (n=n=7), fungal (n=n=5), or viral (n=n=3) co-infection. Among the remaining 10 (40%) cases of HRV monoinfection, patients’ oxygen saturations ranged from 80% to 97% on ambient air, and computed tomography scans showed peribronchiolar, patchy, ground glass infiltrates. CONCLUSIONS: HRV pneumonia is relatively common after HSCT and frequently accompanied by bacterial co-infection. As use of molecular assays for respiratory viral diagnosis becomes widespread, HRV will be increasingly recognized as a significant cause of pneumonia in immunocompromised hosts.


title: The renin–angiotensin–aldosterone system as a link between obesity and coronavirus disease 2019 severity

text: Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory distress coronavirus 2 (SARS‐CoV2), is a rapidly evolving pandemic challenging the world and posing unprecedented public health issues. Current data show that COVID‐19 is associated with increased disease severity in individuals with obesity. Obesity is usually associated with dysregulated renin–angiotensin–aldosterone (RAAS) axis. RAAS has also been implicated in acute lung injury as well as myocardial injury and has thus attracted interest as a potential regulator of COVID‐19 severity. Whilst research all over the world is still struggling to provide a detailed characterization of the biology of SARS‐CoV2 and its associated disease profile, it has become evident that SARS‐CoV2 uses the membrane‐bound form of angiotensin‐converting enzyme 2 (ACE2) as a receptor for cell internalization. ACE2 is a protective component of the RAAS axis and is downregulated after SARS‐CoV2 infection. The RAAS axis could thus be a link between obesity and COVID‐19 severity; therefore, more accurate understanding of the underlying mechanisms would be needed with the hope of proposing efficient therapeutic interventions.


The disguised pandemic: The importance of data normalization in COVID-19 web mapping


title: Clinical education of ethicists: the role of a clinical ethics fellowship

text: BACKGROUND: Although clinical ethicists are becoming more prevalent in healthcare settings, their required training and education have not been clearly delineated. Most agree that training and education are important, but their nature and delivery remain topics of debate. One option is through completion of a clinical ethics fellowship. METHOD: In this paper, the first four fellows to complete a newly developed fellowship program discuss their experiences. They describe the goals, structure, participants and activities of the fellowship. They identify key elements for succeeding as a clinical ethicist and sustaining a clinical ethics program. They critically reflect upon the challenges faced in the program. RESULTS: The one-year fellowship provided real-time clinical opportunities that helped them to develop the necessary knowledge and skills, gain insight into the role and scope of practice of clinical ethicists and hone valuable character traits. CONCLUSION: The fellowship enabled each of the fellows to assume confidently and competently a position as a clinical ethicist upon completion.


title: A Bioethical Perspective for Navigating Moral Dilemmas Amidst the COVID-19 Pandemic

text: The Coronavirus disease 2019 pandemic has been an unprecedented challenge to healthcare systems and clinicians around the globe. As the virus has spread, critical questions arose about how to best deliver health care in emergency situations where material and personnel resources become scarce. Clinicians who excel at caring for the individual patient at the bedside are now being reoriented into a system where they are being asked to see the collective public as their responsibility. As such, the clinical ethics clinicians are used to practicing is being modified by a framework of public health ethics defined by the presence of a global pandemic. There are many unknowns about Coronavirus disease 2019, which makes it difficult to provide consistent recommendations and guidelines that uniformly apply to all situations. This lack of consensus leads to the clinicians' confusion and distress. Real life dilemmas about how to allocate resources and provide care in hot-spot cities make explicit the need for careful ethical analysis, but the need runs far deeper than that; even when not trading some lives against others, the responsibilities of both individual clinicians and the broader healthcare system are changing in the face of this crisis.


title: Changement de tropisme des coronavirus

text: Résumé Le tropisme d’un virus se définit comme l’ensemble des cellules cibles et permissives à ce virus. Le connaître permet de déterminer le ou les organes cibles, ainsi que la ou les espèces animales pouvant être infectées. Le changement de tropisme permet aux virus d’évoluer, notamment en leur permettant de franchir la barrière d’espèce et de s’installer chez un nouvel hôte. Les coronavirus représentent un très large groupe de virus infectant de nombreuses espèces animales. Ces virus à ARN sont dotés d’un potentiel évolutif important, et leur histoire comporte plusieurs exemples de changement de tropisme ayant pour conséquence soit l’émergence d’une nouvelle maladie (coronavirus associé au SRAS, coronavirus respiratoire du porc), soit une nouvelle expression de l’infection (péritonite infectieuse fatale du chat et du furet). Summary Viral tropism is defined as the group of target cells which can be infected by this virus. Knowing viral tropism is knowing the target organ, and the animal species used as host. The variation of tropism allow for virus to evolve, cross species barriers, and infect a new host. Coronavirus family is a very large group of viruses which infect birds and mammals. These RNA viruses can rapidly evolve. In the history of coronaviruses, several examples of variations of tropism have been described, and have as consequences the emergence of a new infection (coronavirus associated with SARS, porcine respiratory coronavirus), or a new expression of the clinical presentation of the infection (fatal infectious peritonitis in cats and ferrets).


title: Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective

text: Owing to the efficacy in reducing pain and inflammation non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines, confirming their position in the WHO’s Model List of Essential Medicines. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications. Although extensive research has elucidated the mechanisms underlying the clinical hazards of NSAIDs, no review has extensively collated the outcomes on various multiorgan toxicities of these drugs together. In this regard, the present review provides a comprehensive insight of the existing knowledge and recent developments on NSAID-induced organ damage. It precisely encompasses the current understanding of structure, classification and mode of action of NSAIDs while reiterating on the emerging instances of NSAID drug repurposing along with pharmacophore modification aimed at safer usage of NSAIDs where toxic effects are tamed without compromising the clinical benefits. The review does not intend to vilify these ‘wonder drugs’; rather provide a careful understanding of their side-effects which would be beneficial in evaluating the risk-benefit threshold while rationally using NSAIDs at safer dose and duration.


title: Antigenic and biological comparisons of bovine coronaviruses derived from neonatal calf diarrhea and winter dysentery of adult cattle

text: The antigenic and biological properties of 6 strains of bovine coronavirus (BCV) derived from neonatal calf diarrhea (CD) and 8 strains of BCV from winter dysentery (WD) of adult cattle, propagated in HRT-18 cells, were compared to determine if CD and WD strains belong to distinct serotypes or subtypes of BCV. All strains hemagglutinated both mouse and chicken erythrocytes at 4 °C, but the ratios of hemagglutination titers with mouse erythrocytes compared to chicken erythrocytes showed diversity for both CD and WD strains. Some CD and WD strains did not hemagglutinate chicken erythrocytes at 37 °C and showed receptor-destroying enzyme activity against chicken erythrocytes. Hyperimmune antisera were produced in guinea pigs against 3 and 7 strains of BCV from CD and WD, respectively. No significant differences in antibody titers against these strains were observed by indirect immunofluorescence tests. However, in virus neutralization tests, antisera to 1 CD and 2 WD strains had 16-fold or lower antibody titers against 3 WD and 1 CD strains than against the homologous strains, and this variation reflected low antigenic relatedness values (R=13–25%), suggesting the presence of different subtypes among BCV. In hemagglutination inhibition tests, some one-way antigenic variations among strains were also observed. These results suggest that some antigenic and biological diversity exists among BCV strains, but these variations were unrelated to the clinical source of the strains; i.e. CD or WD.


A practical approach for the management of obstetric and infertile women during the Phase Two of the Novel Coronavirus Disease 2019 (COVID ‐19) Pandemic


Infection prevention and control measures during COVID‐19 from medical physics perspective: A single institution experience from China


title: Outbreak detection model based on danger theory

text: Abstract In outbreak detection, one of the key issues is the need to deal with the weakness of early outbreak signals because this causes the detection model to have has less capability in terms of robustness when unseen outbreak patterns vary from those in the trained model. As a result, an imbalance between high detection rate and low false alarm rate occurs. To solve this problem, this study proposes a novel outbreak detection model based on danger theory; a bio-inspired method that replicates how the human body fights pathogens. We propose a signal formalization approach based on cumulative sum and a cumulative mature antigen contact value to suit the outbreak characteristic and danger theory. Two outbreak diseases, dengue and SARS, are subjected to a danger theory algorithm; namely the dendritic cell algorithm. To evaluate the model, four measurement metrics are applied: detection rate, specificity, false alarm rate, and accuracy. From the experiment, the proposed model outperforms the other detection approaches and shows a significant improvement for both diseases outbreak detection. The findings reveal that the robustness of the proposed immune model increases when dealing with inconsistent outbreak signals. The model is able to detect new unknown outbreak patterns and can discriminate between outbreak and non-outbreak cases with a consistent high detection rate, high sensitivity, and lower false alarm rate even without a training phase.


title: Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

text: PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I–II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.


title: VADR: validation and annotation of virus sequence submissions to GenBank

text: BACKGROUND: GenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions. RESULTS: We developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on the analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of “alerts” that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBank’s submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Since March 2020, VADR has also been used to check SARS-CoV-2 sequence submissions. Other viruses with high numbers of submissions will be added incrementally. CONCLUSION: VADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allow researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.


COVID-19 Cytokine Storm and Novel Truth


title: Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie – eine Situationsanalyse

text: The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.


Enfermedad pulmonar obstructiva crónica e infección por SARS-CoV-2. ¿Qué sabemos hasta ahora?


title: Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation

text: BACKGROUND: Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. METHODS: Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. RESULTS: Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). CONCLUSIONS: High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.


title: Acute Generalized Exanthematous Pustulosis with Erythema Multiforme‐Like lesions in a COVID‐19 woman

text: The antimalarials, Chloroquine and Hydroxychloroquine (HCQ), and the antivirals Lopinavir/Ritonavir have been recently recorded as having anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) effects.(1) In particular, regarding Italy, one of the countries most affected by the pandemic, the Italian Society of Infectious and Tropical disease (Lombardy section) has recommended the use of HCQ for treatment of coronavirus disease 2019 (COVID‐19).


title: Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Insights from simultaneous familial Kawasaki Disease cases

text: Abstract Recently, an increasing number of patients of SARS-CoV-2 with syndrome which overlaps with Kawasaki Disease (KD) has been reported, supporting the idea that infection is one of triggers of KD. We summarized the reports of simultaneous familial KD cases for understanding etiopathogenesis of both KD and Multisystem Inflammatory Syndrome in Children (MIS-C) related to COVID-19. Here we discuss the etiology of these syndromes from the point of view of infection and genetic susceptibility.


title: Vaccine‐Associated Immune‐Mediated Hemolytic Anemia in the Dog

text: Vaccination has been incriminated as a trigger of immune‐mediated hemolytic anemia (IMHA) in dogs and in people, but evidence to support this association is lacking. In a controlled retrospective study, idiopathic IMHA was identified in 58 dogs over a 27–month period. When compared with a randomly selected control group of 70 dogs (presented for reasons other than IMHA) over the same period, the distribution of cases versus time since vaccination was different (P < .05). Fifteen of the dogs (26%) had been vaccinated within 1 month (mean, 13 days; median, 14 days; range, 1 to 27 days) of developing IMHA (P < .0001), whereas in the control group no marked increase in frequency of presentation was seen in the first month after vaccination. The dogs with IMHA were divided into 2 groups based on time since vaccination: the vaccine IMHA group included dogs vaccinated within 1 month of developing IMHA; the nonvaccine IMHA group included dogs that developed IMHA more than 1 month after vaccination. The recently vaccinated dogs with IMHA (vaccine IMHA group) had significantly lower platelet counts (P < .05) and a trend towards increased prevalence of intravascular hemolysis and autoagglutination when compared with the nonvaccine IMHA group. Similar mortality rates were seen in the vaccine IMHA group (60%) and the nonvaccine IMHA group (44%), with the majority of fatalities (>75%) occurring in the first 3 weeks after presentation. Persistent autoagglutination was a negative prognostic indicator for survival in both groups (P < .05). Presence of icterus and hyperbilirubinemia were negative prognostic indicators for survival in the nonvaccine IMHA group (P < .0001 and P < .01, respectively) but not in the vaccine IMHA group. In the recently vaccinated dogs, combination vaccines from various manufacturers against canine distemper, adenovirus type 2, leptospirosis, parainfluenza, and parvovirus (DHLPP) were involved in each case. Vaccines against rabies virus, Bordetella spp, coronavirus, and Lyme Borrelia were administered concomitantly to some dogs. This study provides the first clinical evidence for a temporal relationship of vaccine‐associated IMHA in the dog.


Thermal cures and COVID-19


title: Estimating a breakpoint in the spread pattern of COVID-19 in South Korea

text: OBJECTIVES: Amid the global COVID-19 crisis, South Korea has been touted for successfully preventing the spread of the infectious disease, which may be due to the aggressive implementation of preventive policies. We evaluated the spread pattern of COVID-19 in South Korea considering the potential impact of policy interventions on transmission rates. METHODS: The SIR (Susceptible-Infected-Removed) model with a breakpoint that allows a change in transmission rate at an unknown point was proposed. Estimated trajectories of COVID-19 from SIR models with and without a breakpoint were compared. RESULTS: The proposed model with a break fitted the actual series of infection case much better than the classic model. The estimated breakpoint was March 7(th) and the transmission rate dropped by 0.23 after the breakpoint. A counterfactual study based on our estimate indicated that the number of the infected could reach 2,500,000 compared to the peak of 8,000 in the observed series. CONCLUSIONS: It is critical to consider a change in the transmission rate to evaluate the spread trajectory of COVID-19 in South Korea. Our estimation and counterfactual experiments indicate that public health interventions may play a role in determining the spread pattern of infectious diseases.


title: The impact of macroeconomic and non-macroeconomic forces on hotel stock returns

text: Abstract This study aimed to examine the relationship between macroeconomic and non-macroeconomic variables and hotel stock returns using hotel companies listed on the Taiwan Stock Exchange. The regression analysis indicated that among the macroeconomic variables (i.e., money supply, the growth rate of industrial production, expected inflation, the change of unemployment rate, and the yield spread), only money supply and the unemployment rate significantly explained the movement of hotel stock returns. On the other hand, all non-macroeconomic forces selected (i.e., presidential elections, the 921 earthquake, the 2003 Iraqi war, the outbreak of SARS, sports mega-events, the Asian financial crisis, and the 911 terrorist attacks) had significant influences on the hotel stock returns. The empirical results of this study may be used as valuable information for local and global stock investors who seek an investment opportunity in the hospitality industry.


title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication

text: NTP-motif, a consensus sequence previously shown to be characteristic of numerous NTP-utilizing enzymes, was identified in nonstructural proteins of several groups of positive-strand RNA viruses. These groups include picorna-, alpha-, and coronaviruses infecting animals and como-, poty-, tobamo-, tricorna-, hordei-, and furoviruses of plants, totalling 21 viruses. It has been demonstrated that the viral NTP-motif-containing proteins constitute three distinct families, the sequences within each family being similar to each other at a statistically highly significant level. A lower, but still valid similarity has also been revealed between the families. An overall alignment has been generated, which includes several highly conserved sequence stretches. The two most prominent of the latter contain the socalled “A” and “B” sites of the NTP-motif, with four of the five invariant amino acid residues observed within these sequences. These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. In this group the “A” and “B” sites of the NTP-motif are the most conserved sequences and, by inference, should play the principal role in the functioning of the proteins. A hypothesis is proposed that all these proteins posses NTP-binding capacity and possibly NTPase activity, performing some NTP-dependent function in viral RNA replication. The importance of phylogenetic analysis for the assessment of the significance of the occurrence of the NTP-motif (and of sequence motifs of this sort in general) in proteins is emphasized.


Virtual drug testing: redefining sample collection in a global pandemic


title: Occupational Health Science in the Time of COVID-19: Now more than Ever

text: Workers bear a heavy share of the burden of how countries contend with COVID-19; they face numerous serious threats to their occupational health ranging from those associated with direct exposure to the virus to those reflecting the conflicts between work and family demands. Ten experts were invited to comment on occupational health issues unique to their areas of expertise. The topics include work-family issues, occupational health issues faced by emergency medical personnel, the transition to telework, discrimination against Asian-Americans, work stressors, presenteeism, the need for supportive supervision, safety concerns, economic stressors, and reminders of death at work. Their comments describe the nature of the occupational health concerns created by COVID-19 and discuss both unanswered research questions and recommendations to help organizations reduce the impacts of COVID-19 on workers.


Report of the fifth symposium on emerging viral diseases


title: Preventive behaviors, beliefs, and anxieties in relation to the swine flu outbreak among college students aged 18–24 years

text: AIM: The objective of this study was to assess beliefs, misconception, and anxiety in relation to swine flu outbreak and whether perception of the outbreak predicted changes in behavior. SUBJECT AND METHODS: In November 2009, we conducted an Internet-based cross-sectional survey of college students aged 18–24 years in a Midwestern State in the USA. We collected information on swine flu knowledge, perception on immunization safety, perceived efficacy of recommended behavior, changed behavior, and anxiety. RESULTS: Of the 236 respondents, 83.1% had some anxiety about swine flu, 64.8% believed avoiding crowded places was preventive, 33.5% believed the 2009 swine flu vaccine was safe, and 36.9% showed interest in receiving the vaccine. Misconceptions about swine flu contagion via eating cooked pork, water sources, and insect bites were common. Respondents were unaware of transmissions via contaminated objects and droplets. Only 42.6% were satisfied with governmental efforts. Women were more likely to wash hands frequently than men (odds ratio 2.80, p < 0.001). CONCLUSION: There is a gap in swine flu knowledge, minimal risk reduction, increased amount of anxiety, and skepticism about swine flu vaccine safety. These gaps warrant serious attention to inform the public about specific actions regarding swine flu.


title: Time to restart: A comparative compilation of triage recommendations in dentistry during the Covid −19 pandemic

text: BACKGROUND: The novel coronavirus (COVID-19) pandemic has become a enormous challenge for the health care facilitators. It has significantly affected the dental professionals in their clinical practices, hospitals and even dental schools. Due to the risk of cross – infection involved within in the dental setting, the dental professional is even scared to provide emergent treatment for a patient. AIM: The aim of this comparative review is to throw light on the essential knowledge that a clinician must acquire before triaging a patient, understanding the case definition of COVID-19 and preparedness required before planning to re-open the dental practices. METHODOLOGY: The updated database obtained from various governmental and non-governmental official webpages were rapidly analysed up till May 31, 2020. CONCLUSION: This compilation of recommendations and guidance laid by various authorities across the world will function as a foundation for safer dental practice within the future.


The Economic and Public Health Imperatives Around Making Potential Coronavirus Disease–2019 Treatments Available and Affordable


title: First assessment of microbial diversity in faecal microflora of Eurasian otter (Lutra lutra Linnaeus, 1758) in Portugal

text: The Eurasian otter (Lutra lutra Linnaeus, 1758), a predator from the Order Carnivora, Family Mustelidae, evolved the ability to swim and forage in water, being an important element of biodiversity. Otters are widely spread through Portugal, and scats have been extensively used in ecology studies; however, valid information on their microbiota is scarce. This work represents a first approach to characterise the otter faecal microflora in samples collected in river stretches of the Sado river basin (Portugal) during winter 2006. Eight sampling stretches of 8 km were selected, and from each, six to eight sampling sites were visited. A total of 31 scats were analysed. The microflora studied included aerobic bacteria, spore-forming anaerobic bacteria and viruses (coronavirus, parvovirus, adenovirus, parainfluenza virus). Bacterial isolates were identified based on morphology and metabolic pathways, and virus detection was performed by polymerase chain reaction. The results revealed the high degree of bacterial diversity in the faecal microflora of L. lutra. A total of 88 Gram-negative (23 genera) and 44 Gram-positive isolates (ten genera) were identified. The identification of four isolates was inconclusive, and their identification was performed by 16S ribosomal ribonucleic acid sequencing, which confirms the need for biochemical testing optimisation regarding animal isolates. None of the scats was positive for virus detection. Identification of otter faecal microflora and of potential pathogens is an important first step towards understanding and monitoring their importance in otter population health.


title: Comprehensive analysis of the codon usage patterns in the envelope glycoprotein E2 gene of the classical swine fever virus

text: The classical swine fever virus (CSFV), circulating worldwide, is a highly contagious virus. Since the emergence of CSFV, it has caused great economic loss in swine industry. The envelope glycoprotein E2 gene of the CSFV is an immunoprotective antigen that induces the immune system to produce neutralizing antibodies. Therefore, it is essential to study the codon usage of the E2 gene of the CSFV. In this study, 140 coding sequences of the E2 gene were analyzed. The value of effective number of codons (ENC) showed low codon usage bias in the E2 gene. Our study showed that codon usage could be described mainly by mutation pressure ENC plot analysis combined with principal component analysis (PCA) and translational selection-correlation analysis between the general average hydropathicity (Gravy) and aromaticity (Aroma), and nucleotides at the third position of codons (A3s, T3s, G3s, C3s and GC3s). Furthermore, the neutrality analysis, which explained the relationship between GC12s and GC3s, revealed that natural selection had a key role compared with mutational bias during the evolution of the E2 gene. These results lay a foundation for further research on the molecular evolution of CSFV.


title: Antiviral activity of Aloe hijazensis against some haemagglutinating viruses infection and its phytoconstituents

text: Evaluation of the antiviral activities of flowers, flower-peduncles, leaves, and roots of Aloe hijazensis against haemagglutinating viruses of avian paramyxovirus type-1 (APMV-1), avian influenza virus type A (AI-H5N1), Newcastle disease virus (NDV), and egg-drop syndrome virus (EDSV) in specific pathogen free (SPF) chicken embryos were carried out. Extract of the flowers and leaves showed relatively higher activity than the extracts of other plant parts. Thirteen compounds were isolated from both the flowers and flower-peduncles of A. hijazensis. The isolated compounds were classified into: five anthraquinones; ziganein, ziganein-5-methyl ether, aloesaponarin I, chrysophanol, aloe-emodin, one dihydroisocoumarin; feralolide, four flavonoids; homoplantaginin, isoorientin, luteolin 7-glucuronopyranoside, isovitexin, one phenolic acid; p-coumaric acid, the anthrone; barbaloin together with aloenin. Eleven compounds were attributed to the flowers and seven to the flower-peduncles. Homoplantaginin and luteolin 7-glucuronopyranoside are reported here for the first time from Aloe spp. To the best of our knowledge, this is the first report on the chemical composition and biological activity of those plant parts.


title: Functional characteristics of patients with SARS-CoV-2 pneumonia at 30 days post infection

text: More than half of patients with Covid-19 pneumonia exhibit abnormal lung function 30 days after symptoms onset, without clear relationship with pneumonia extent on chest-CT. This pleads for systematic and long-term follow-up of patients with Covid.


title: COVID-19 and forced alcohol abstinence in India: The dilemmas around ethics and rights

text: In response to the COVID-19 pandemic, as with other countries across the world, the Central and State Governments of India initiated several measures to slow down the spread of the virus and to ‘flatten the curve’. One such measure was a ‘total lockdown’ for several weeks across the country. A complex and unexpected outcome of the lockdown which has medical, ethical, economic, and social dimensions is related to alcohol consumption. The lockdown and consequent acute non-availability of alcohol resulted in people with alcohol dependence going into withdrawals, black marketing of alcohol, and in extreme cases suicide resulting from the alleged frustration of not having access to alcohol. The health dilemmas around this situation are biological (e.g. pushing people into risky situations-potentially fatal alcohol withdrawal, consumption of illicit or other non-consumable alcohol) and psychosocial (e.g. isolation increasing the risk of relapses, loss of control over the decision to abstain which can be detrimental to recovery, restriction of access to services for alcohol problems). The legal and rights-related dilemmas are centred around whether States have the right to impinge on individual autonomy on the grounds of public health, the capacity of the health systems to provide appropriate services to cope with those who will struggle with the unavailability of alcohol, the constitutionality of the Central government's impinging on jurisdiction of states under the guise of a health emergency caused by the pandemic, and the ability of the State to make unbiased decisions about this issue when it is highly dependent on the revenue from the sale of alcohol and associated industries. The way forward could be a pragmatic and utilitarian approach involving continued access to alcohol, while observing all physical distancing norms necessary during the pandemic, for those who want to continue drinking; and implementing innovative measures such as tele-counselling for those who wish not to return back to drinking.


title: Individual sequences in large sets of gene sequences may be distinguished efficiently by combinations of shared sub-sequences

text: BACKGROUND: Most current DNA diagnostic tests for identifying organisms use specific oligonucleotide probes that are complementary in sequence to, and hence only hybridise with the DNA of one target species. By contrast, in traditional taxonomy, specimens are usually identified by 'dichotomous keys' that use combinations of characters shared by different members of the target set. Using one specific character for each target is the least efficient strategy for identification. Using combinations of shared bisectionally-distributed characters is much more efficient, and this strategy is most efficient when they separate the targets in a progressively binary way. RESULTS: We have developed a practical method for finding minimal sets of sub-sequences that identify individual sequences, and could be targeted by combinations of probes, so that the efficient strategy of traditional taxonomic identification could be used in DNA diagnosis. The sizes of minimal sub-sequence sets depended mostly on sequence diversity and sub-sequence length and interactions between these parameters. We found that 201 distinct cytochrome oxidase subunit-1 (CO1) genes from moths (Lepidoptera) were distinguished using only 15 sub-sequences 20 nucleotides long, whereas only 8–10 sub-sequences 6–10 nucleotides long were required to distinguish the CO1 genes of 92 species from the 9 largest orders of insects. CONCLUSION: The presence/absence of sub-sequences in a set of gene sequences can be used like the questions in a traditional dichotomous taxonomic key; hybridisation probes complementary to such sub-sequences should provide a very efficient means for identifying individual species, subtypes or genotypes. Sequence diversity and sub-sequence length are the major factors that determine the numbers of distinguishing sub-sequences in any set of sequences.


title: Serological Diagnosis of Flavivirus-Associated Human Infections

text: Arthropod-borne viruses (arboviruses) belonging to the Flavivirus genus of the Flaviviridae family, are a major public health threat in tropical and subtropical regions, and have recently become a medical concern in temperate zones. Most flaviviruses are classified as zoonotic viruses. Human flavivirus infections can be asymptomatic, responsible for unspecific symptoms in the first few days following infection, or responsible for severe complications potentially resulting in death. During the first days following symptom onset, laboratory diagnosis of acute human flavivirus infection is mainly based on molecular detection of the viral genome by RT-PCR methods, followed by the capture of specific antibodies using serological tests after the first week of infection. The detection of antibodies that have virus neutralizing activity can be used to confirm flavivirus infection. However, human flavivirus infections induce the production of cross-reactive antibodies, often making serology inconclusive. Indeed, serological diagnosis of flavivirus infection can be hampered by a patient’s history of flavivirus exposure, particularly in regions where multiple antigenically related flaviviruses co-circulate. We focus our mini review on conventional immunoassays that allow the diagnosis of major flavivirus-associated human infections in basic, routine and high-profile central health centers; and the interpretation of diagnostic serology tests for patients living within different epidemiological situations.


title: Gilles de la Tourette Syndrome: advice in the times of COVID-19

text: The novel coronavirus disease (COVID-19) was identified as the cause of an outbreak of respiratory disease in China at the end of 2019. It then spread with enormous rapidity and by mid-March 2020 was declared a world pandemic. Gilles de la Tourette Syndrome (GTS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 1% of the population. The clinical symptoms include multiple motor and one or more phonic (vocal) tics. Germane to this communication is that 85% of patients with GTS have associated psychiatric co-morbidities, many of which are being exacerbated in the current global health crisis. In addition, several symptoms of GTS may mimic COVID-19, such as a dry cough and sniffing (phonic tics), while other symptoms such as spitting, inappropriate touching of others and “non-obscene socially inappropriate symptoms” can potentially get patients with GTS into trouble with the law. We suggest that a clear explanation of the COVID-19 illness and GTS is important to enable colleagues of various specialities who tend to patients with GTS. It is important to acknowledge at the outset that the information available on the COVID-19 pandemic changes daily, including cases infected, deaths reported, and how various national health systems are planning and or coping or not. It is fair to say that having read the current medical and lay press we conclude that it is not easy to reassure our patients with absolute certainty. However, notwithstanding that, we hope our documentation is of some assistance.


title: Post-SARS tourist arrival recovery patterns: An analysis based on a catastrophe theory

text: In 2003, the Severe Acute Respiratory Syndrome (SARS) ravaged many Asian countries. The outbreak of SARS caused a crisis in the tourism industry in many parts of Asia in that year. The purpose of this study is to examine and to compare the post-SARS recovery patterns of inbound arrivals from Japan, Hong Kong and USA in Taiwan. Taking the cusp catastrophe model as its foundation, this study proposes a well-grounded approach to understanding the nature of the recovery processes and to explaining the difference between the recovery patterns displayed by arrivals from Japan and those from Hong Kong and USA. Implications regarding tourism promotion policies are drawn from the analysis.


title: Genetic characterization of porcine epidemic diarrhea virus in Korea from 1998 to 2013

text: The number of porcine epidemic diarrhea (PED) cases has increased over the past 20 years in Korea, with a major outbreak in 2013. A total of 27 Korean strains from 1998 to 2013 were analyzed (excluding the noncoding regions) and divided into two groups for comparison of the spike (S), ORF3, envelope (E), membrane (M), and nucleocapsid (N) genes with those of reference strains, vaccine strains, and previously identified strains based on phylogenetic analysis. Analysis of the selection patterns of PEDV isolated in Korea indicated positive selection of nine nonsynonymous sites in the S and N proteins and negative selection at 97 sites for all of the proteins. Interestingly, eight nonsynonymous mutations in S showed no significant pattern change over the 15-year period, and one of eight mutation sites was found only in IC05TK, GN05DJ, and KNU0802 in the epidemic years 2005 and 2008. These eight mutations were also present during the epidemic years in China. Furthermore, of the signs of positive selection in the S protein, the conservative substitutions were more frequent than radical substitutions in PEDVs, suggesting that the evolution of Korean strains has been slow. Serological cross-reactivity was detected between three field PEDVs and two vaccine strains, with different serum neutralization titers. In conclusion, although Korean PEDVs have been evolving slowly, their diverse antigenicity and genetics imply that multilateral efforts to prevent future PED outbreaks are required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-015-2353-y) contains supplementary material, which is available to authorized users.


title: Serious Adverse Events Associated With Hydroxychloroquine Amidst COVID-19 Pandemic: Case Series and Literature Review

text: COVID-19 represents a global health crisis. Several studies are evaluating potential therapies including hydroxychloroquine (HCQ) which is given to patients based on limited observational evidence. However, it can cause serious adverse events. Moreover, recent studies showed no benefits due to HCQ. We present two COVID-19 patients treated with HCQ and had adverse events.


title: Characterization of peritoneal cells from cats with experimentally-induced feline infectious peritonitis (FIP) using RNA-seq

text: Laboratory cats were infected with a serotype I cat-passaged field strain of FIP virus (FIPV) and peritoneal cells harvested 2–3 weeks later at onset of lymphopenia, fever and serositis. Comparison peritoneal cells were collected from four healthy laboratory cats by peritoneal lavage and macrophages predominated in both populations. Differential mRNA expression analysis identified 5621 genes as deregulated in peritoneal cells from FIPV infected versus normal cats; 956 genes showed > 2.0 Log(2) Fold Change (Log(2)FC) and 1589 genes showed < −2.0 Log(2)FC. Eighteen significantly upregulated pathways were identified by InnateDB enrichment analysis. These pathways involved apoptosis, cytokine–cytokine receptor interaction, pathogen recognition, Jak-STAT signaling, NK cell mediated cytotoxicity, several chronic infectious diseases, graft versus host disease, allograft rejection and certain autoimmune disorders. Infected peritoneal macrophages were activated M1 type based on pattern of RNA expression. Apoptosis was found to involve large virus-laden peritoneal macrophages more than less mature macrophages, suggesting that macrophage death played a role in virus dissemination. Gene transcripts for MHC I but not II receptors were upregulated, while mRNA for receptors commonly associated with virus attachment and identified in other coronaviruses were either not detected (APN, L-SIGN), not deregulated (DDP-4) or down-regulated (DC-SIGN). However, the mRNA for FcγRIIIA (CD16A/ADCC receptor) was significantly upregulated, supporting entry of virus as an immune complex. Analysis of KEGG associated gene transcripts indicated that Th1 polarization overshadowed Th2 polarization, but the addition of relevant B cell associated genes previously linked to FIP macrophages tended to alter this perception.


title: Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors

text: Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.


title: Current and Emerging Therapeutics for Neuromyelitis Optica Spectrum Disorder: Relevance to the COVID-19 Pandemic

text: Neuromyelitis optica spectrum disorder (NMOSD) can lead to immobility and bulbar weakness. This, in addition to the older age of onset and the higher rate of hospitalization compared to multiple sclerosis, makes this patient group a potential target for complicated COVID-19 infection. Moreover, many of the commonly used preventive therapies for NMOSD are cell-depleting immunouppsressants with increased risk of viral and bacterial infections. The emergence of several new NMOSD therapeutics, including immune-modulating agents, concurrently with the worldwide spread of the COVID-19 global pandemic call for careful therapeutic planning and add to the complexity of NMOSD management. Altering the common therapeutic approach to NMOSD during the pandemic may be necessary to balance both efficacy and safety of treatment. Selection of preventive therapy should take in consideration the viral exposure risk related to the route and frequency of administration and, most importantly, the immunological properties of each therapeutic agent and its potential impact on the risk of SARS-CoV-2 susceptibility and severity of infection. The impact of the therapeutic agent on the immune response against the future SARS-CoV-2 vaccine should also be considered in the clinical decision-making. In this review, we will discuss the immune response against SARS-CoV-2 and evaluate the potential impact of the current and emerging NMOSD therapeutics on infection risk, infection severity, and future SARS-CoV-2 vaccination. We propose a therapeutic approach to NMOSD during the COVID-19 pandemic based on analysis of the mechanism of action, route of administration, and side effect profile of each therapeutic agent.


title: Establishment and Application of a Universal Coronavirus Screening Method Using MALDI-TOF Mass Spectrometry

text: There are four human coronaviruses (HCoVs), distributed worldwide, that are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV shows that HCoVs pose a significant threat to human health. Our work aims to develop a sensitive method (mCoV-MS) which can not only identify known HCoVs accurately, but also have the ability to provide clues for the emerging HCoVs. The method was performed using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. We developed a 17-plex analysis to detect six HCoVs in Panel A and another 17-plex analysis to detect Alphacoronavirus and Betacoronavirus in Panel B. All tested primers and probes for the mCoV-MS method were effective, with no cross-reactivity observed with other common respiratory viruses. To confirm the usefulness of the mCoV-MS method we screened 384 pharyngeal and/or anal swab samples collected from bats/rodents, and 131 nasal and throat swabs from human patients. The results showed good concordance with the results of metagenomic analysis or PCR-sequencing. The validation test showed mCoV-MS method can detect potentially pathogenic CoVs in Alphacoronavirus and Betacoronavirus and provide convincingly phylogenetic evidences about unknown CoVs. The mCoV-MS method is a sensitive assay that is relatively simple to carry out. We propose that this method be used to complement next generation sequencing technology for large-scale screening studies.


title: Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Plant Virus Replication

text: Positive-sense (+) RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+) RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D) imaging technologies, such as electron tomography (ET) and focused ion beam-scanning electron microscopy (FIB-SEM), has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.


title: Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1)

text: BACKGROUND: Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to − 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. METHODS: In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1–4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1–4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). RESULTS: From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. CONCLUSION: This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1–3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12985-018-0925-7) contains supplementary material, which is available to authorized users.


title: Chapter 3 Early Stages of Infection After Pathogen Entry

text: In this chapter, we describe the early stages of the pathogenic cycle involving entry into the host. For example, some bacteria may enter into epithelial cells, proliferate and then spread at the epithelial surface before being transmitted to another host. Some pathogens then migrate past the epithelial layer to deeper tissues causing invasive infections. Examples of some of the major bacterial, viral and fungal pathogens affecting the epithelial surfaces in the body are provided. The body produces a strong inflammatory immune response to pathogens at the epithelial surface. An introduction to the components of the inflammatory response including the phagocytic cells and the lymphatic system is provided. In addition, the nutritional requirements for invading bacteria including the importance of iron is discussed.


title: Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

text: Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.


title: Coronavirus disease (COVID-19) and fertility: viral host entry protein expression in male and female reproductive tissues

text: Abstract Objective To identify cell types in the male and female reproductive systems at risk of SARS-CoV-2 infection due to expression of host genes and proteins used by the virus for cell entry. Design Descriptive analysis of transcriptomic and proteomic data. Setting Academic research department and clinical diagnostic laboratory. Patients/Animals None. Focused on previously generated gene and protein expression data. Intervention(s) None. Main Outcome Measure(s) Identification of cell types co-expressing the key ACE2 and TMPRSS2 genes and proteins, as well as other candidates potentially involved in SARS-CoV-2 cell entry. Results Based on single cell RNA sequencing data, co-expression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. A subpopulation of oocytes in non-human primate ovarian tissue were found to express ACE2 and TMPRSS2, but co-expression was not observed in ovarian somatic cells. RNA expression of TMPRSS2 in 18 samples of human cumulus cells was shown to be low or absent. There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial and placental cells. Conclusion These analyses suggest that SARS-CoV-2 infection is unlikely to have long-term effects on male and female reproductive function. While the results cannot be considered definitive they imply that procedures in which oocytes are collected and fertilized in vitro are associated with very little risk of viral transmission from gametes to embryos and may indeed have the potential to minimize exposure of susceptible reproductive cell types to infection when compared to natural conception.


title: Hepatitis E Virus Replication

text: Hepatitis E virus (HEV) is a small quasi-enveloped, (+)-sense, single-stranded RNA virus belonging to the Hepeviridae family. There are at least 20 million HEV infections annually and 60,000 HEV-related deaths worldwide. HEV can cause up to 30% mortality in pregnant women and progress to liver cirrhosis in immunocompromised individuals and is, therefore, a greatly underestimated public health concern. Although a prophylactic vaccine for HEV has been developed, it is only licensed in China, and there is currently no effective, non-teratogenic treatment. HEV encodes three open reading frames (ORFs). ORF1 is the largest viral gene product, encoding the replicative machinery of the virus including a methyltransferase, RNA helicase, and an RNA-dependent RNA polymerase. ORF1 additionally contains a number of poorly understood domains including a hypervariable region, a putative protease, and the so-called ‘X’ and ‘Y’ domains. ORF2 is the viral capsid essential for formation of infectious particles and ORF3 is a small protein essential for viral release. In this review, we focus on the domains encoded by ORF1, which collectively mediate the virus’ asymmetric genome replication strategy. We summarize what is known, unknown, and hotly debated regarding the coding and non-coding regions of HEV ORF1, and present a model of how HEV replicates its genome.


title: Pathogen seasonality and links with weather in England and Wales: a big data time series analysis

text: BACKGROUND: Many infectious diseases of public health importance display annual seasonal patterns in their incidence. We aimed to systematically document the seasonality of several human infectious disease pathogens in England and Wales, highlighting those organisms that appear weather-sensitive and therefore may be influenced by climate change in the future. METHODS: Data on infections in England and Wales from 1989 to 2014 were extracted from the Public Health England (PHE) SGSS surveillance database. We conducted a weekly, monthly and quarterly time series analysis of 277 pathogen serotypes. Each organism’s time series was forecasted using the TBATS package in R, with seasonality detected using model fit statistics. Meteorological data hosted on the MEDMI Platform were extracted at a monthly resolution for 2001–2011. The organisms were then clustered by K-means into two groups based on cross correlation coefficients with the weather variables. RESULTS: Examination of 12.9 million infection episodes found seasonal components in 91/277 (33%) organism serotypes. Salmonella showed seasonal and non-seasonal serotypes. These results were visualised in an online Rshiny application. Seasonal organisms were then clustered into two groups based on their correlations with weather. Group 1 had positive correlations with temperature (max, mean and min), sunshine and vapour pressure and inverse correlations with mean wind speed, relative humidity, ground frost and air frost. Group 2 had the opposite but also slight positive correlations with rainfall (mm, > 1 mm, > 10 mm). CONCLUSIONS: The detection of seasonality in pathogen time series data and the identification of relevant weather predictors can improve forecasting and public health planning. Big data analytics and online visualisation allow the relationship between pathogen incidence and weather patterns to be clarified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5931-6) contains supplementary material, which is available to authorized users.


title: Modeling monthly flows of global air travel passengers: An open-access data resource

text: Abstract The global flow of air travel passengers varies over time and space, but analyses of these dynamics and their integration into applications in the fields of economics, epidemiology and migration, for example, have been constrained by a lack of data, given that air passenger flow data are often difficult and expensive to obtain. Here, these dynamics are modeled at a monthly scale to provide an open-access spatio-temporally resolved data source for research purposes (www.vbd-air.com/data). By refining an annual-scale model of Huang et al. (2013), we developed a set of Poisson regression models to predict monthly passenger volumes between directly connected airports during 2010. The models not only performed well in the United States with an overall accuracy of 93%, but also showed a reasonable confidence in estimating air passenger volumes in other regions of the world. Using the model outcomes, this research studied the spatio-temporal dynamics in the world airline network (WAN) that previous analyses were unable to capture. Findings on the monthly variation of WAN offer new knowledge for dynamic planning and strategy design to address global issues, such as disease pandemics and climate change.


COVID-19 and vitamin D—Is there a link and an opportunity for intervention?


title: CANCER IN THE TIME OF COVID: Expert opinion on how to adapt current practice

text: The susceptibility of cancer patients to adverse outcome of viral infections is well known from past experiences, e.g. Influenza increasing the risk of hospital admission with respiratory distress four times, and the risk of death ten times, compared to patients without cancer [1].


title: IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner

text: The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures.


title: Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys

text: BACKGROUND: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. METHODS: Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). RESULTS: Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. CONCLUSIONS: Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.


title: Throat and nasal swabs for molecular detection of respiratory viruses in acute pharyngitis

text: BACKGROUND: Detection of specific respiratory viruses is important for surveillance programs, where nasopharyngeal or nasal swabs have traditionally been used. Our objective was to determine whether sampling with a throat swab provides incremental benefit—when used in conjunction with a nasal swab—to detect respiratory viruses among patients with acute pharyngitis in the outpatient setting. FINDINGS: Among 83 university students with acute pharyngitis, we detected respiratory viruses with molecular assays on two samples collected per student: with a flocked nasal mid-turbinate swab and a rayon throat swab. Forty-eight (58 %) patients had virus-positive samples, with 49 virus positives detected by either swab (one patient had a dual viral co-infection). The most common viruses were rhinovirus, coronavirus, and influenza A virus. Specifically, 29 virus positives were detected by both swabs, 14 exclusively by the nasal swab, and six exclusively by the throat swab. The additional six virus positives detected by the throat swab corresponded to an absolute increase in viral detection of 7.1 % (95 % CI: 1.2–12.9 %); the specific viruses detected were four rhinoviruses and two coronaviruses. CONCLUSIONS: The flocked nasal swab samples respiratory viruses well, even among patients whose primary complaint is a sore throat. The rayon throat swab has modest incremental value over and above using the flocked nasal mid-turbinate swab alone, which suggests that while throat swabs alone would not be adequate for respiratory viral surveillance, they may have value as a supplementary test.


COVID‐19 in dimethyl fumarate‐treated patients with multiple sclerosis


title: EVOLUTION AND MEDICINE IN UNDERGRADUATE EDUCATION: A PRESCRIPTION FOR ALL BIOLOGY STUDENTS

text: The interface between evolutionary biology and the biomedical sciences promises to advance understanding of the origins of genetic and infectious diseases in humans, potentially leading to improved medical diagnostics, therapies, and public health practices. The biomedical sciences also provide unparalleled examples for evolutionary biologists to explore. However, gaps persist between evolution and medicine, for historical reasons and because they are often perceived as having disparate goals. Evolutionary biologists have a role in building a bridge between the disciplines by presenting evolutionary biology in the context of human health and medical practice to undergraduates, including premedical and preprofessional students. We suggest that students will find medical examples of evolution engaging. By making the connections between evolution and medicine clear at the undergraduate level, the stage is set for future health providers and biomedical scientists to work productively in this synthetic area. Here, we frame key evolutionary concepts in terms of human health, so that biomedical examples may be more easily incorporated into evolution courses or more specialized courses on evolutionary medicine. Our goal is to aid in building the scientific foundation in evolutionary biology for all students, and to encourage evolutionary biologists to join in the integration of evolution and medicine.


title: Autophagy induced by bovine viral diarrhea virus infection counteracts apoptosis and innate immune activation

text: Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP) and cytopathic (CP). One strategy that has been used to treat or prevent virus-associated diseases is the modulation of autophagy, which is used by the innate immune system to defend against viral infection; however, at present, the interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B) with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient MDBKs (shBCN1-MDBK cells) were constructed. Then MDBK, GFP-LC3-MDBK and shBCN1-MDBK cells were infected with CP or NCP BVDV strains. The LC3-II turnover rate was estimated by western blot, autophagosomes were visualized by confocal microscopy, and ultrastructural analysis was performed using electron microscopy. Autophagy flux was observed using chloroquine as an inhibitor of the autophagic process. The influence of autophagy on BVDV replication and release was investigated using virus titration, and its effect on cell viability was also studied. The effect of BVDV-induced autophagy on the survival of BVDV-infected host cell, cell apoptosis, and interferon (IFN) signalling was studied by flow cytometric analysis and quantitative RT-(q)PCR using shBCN1-MDBK cells. we found that infection with either CP or NCP BVDV strains induced steady-state autophagy in MDBK cells, as evident by the increased number of double- or single-membrane vesicles, the accumulation of GFP- microtubule-associated protein 1 light chain 3 (LC3) dots, and the conversion of LC3-I (cytosolic) to LC3-II (membrane-bound) forms. The complete autophagic process was verified by monitoring the LC3-II turnover ratio, lysosomal delivery, and proteolysis. In addition, we found that CP and NCP BVDV growth was inhibited in MDBK cells treated with high levels of an autophagy inducer or inhibitor, or in autophagy deficient-MDBK cells. Furthermore, our studies also suggested that CP and NCP BVDV infection in autophagy-knockdown MDBK cells increased apoptotic cell death and enhanced the expression of the mRNAs for IFN-α, Mx1, IFN-β, and OAS-1 as compared with control MDBK cells. Our study provides strong evidence that BVDV infection induces autophagy, which facilitates BVDV replication in MDBK cells and impairs the innate immune response. These findings might help to illustrate the pathogenesis of persistent infection caused by BVDV.