title: Malay Version of the Fear of COVID-19 Scale: Validity and Reliability

text: The newly developed Persian Fear of COVID-19 Scale (FCV-19S) is a seven-item uni-dimensional scale that assesses the severity of fear of COVID-19. A translation and validation of the FCV-19S in the Malay language was expedited due to the severe psychological sequelae of COVID-19 in Malaysia. Formal WHO forward and backward translation sequences were employed in translating the English version into Malay. Malaysian university participants were recruited via convenience sampling online using snowball methods. The reliability and validity properties of the Malay FCV-19S were rigorously psychometrically evaluated (utilising both confirmatory factor analysis and Rasch analysis) in relation to socio-demographic variables and response to the depression, anxiety and stress subscales of the Malay validation of the DASS-21. The sample comprised 228 Malaysian participants. The Cronbach α value for the Malay FCV-19S was 0.893 indicating very good internal reliability. The results of the confirmatory factor analysis showed that the uni-dimensional factor structure of the FCV19S fitted well with the data. The FCV-19S-M was significantly correlated with anxiety (r = 0.481, p < 0.001) and stress (r = 0.389, p < 0.001) subscales of DASS-21. The FCV-19S-M’s properties tested using Rasch analysis were also satisfactory. Hence, the Malay FCV-19S is valid and reliable, with robust psychometric properties from classical and modern psychometric methods. It therefore is a highly crucial and timely addition to the psychological toolkit both in operational and research settings in identifying, managing and responding to the psychological distress engendered by COVID-19.


title: Molecular epidemiology of a post‐influenza pandemic outbreak of acute respiratory infections in Korea caused by human adenovirus type 3

text: An outbreak of upper respiratory tract infections associated with human adenovirus (HAdV) occurred on a national scale in Korea from September to December 2010, following a major H1N1 influenza pandemic. Data from the Korea Influenza and Respiratory Surveillance System (KINRESS) showed an unusually high positive rate accounting for up to 20% of all diagnosed cases. To determine the principal cause of the outbreak, direct polymerase chain reaction (PCR) amplification followed by sequence analysis targeting parts of the hexon gene of HAdV was performed. Serotypes of 1,007 PCR‐diagnosed HAdV‐positive samples from patients with an acute upper respiratory tract illness were determined and epidemiological characteristics including major aged group and clinical symptoms were analyzed. The principal symptom of HAdV infections was fever and the vulnerable aged group was 1–5 years old. Based on sequence analysis, HAdV‐3 was the predominant serotype in the outbreak, with an incidence of 74.3%. From the beginning of 2010 until May, the major serotypes were HAdV‐1, 2, and 5 (70–100%) in any given period. However, an outbreak dominated by HAdV‐3 started between July and August and peaked in September. Phylogenetic analysis revealed that there was no genetic variation in HAdV‐3. The results demonstrated that an outbreak of upper respiratory illness followed by H1N1 influenza pandemic in Korea was caused mainly by emerged HAdV‐3. J. Med. Virol. 87: 10–17, 2015. © 2014 Wiley Periodicals, Inc.


title: Prevalence of feline infectious peritonitis in specific cat breeds

text: Although known that purebreed cats are more likely to develop feline infectious peritonitis (FIP), previous studies have not examined the prevalence of disease in individual breeds. All cats diagnosed with FIP at a veterinary teaching hospital over a 16-year period were identified. Breed, sex and reproductive status of affected cats were compared to the general cat population and to mixed breed cats evaluated during the same period. As with previous studies sexually intact cats and purebreed cats were significantly more likely to be diagnosed with FIP; males and young cats also had a higher prevalence of disease. Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of FIP. Although additional factors doubtlessly influence the relative prevalence of FIP, this study provides additional guidance when prioritizing differentials in ill purebreed cats.


title: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response

text: PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.


title: Viral Pneumonia and Acute Respiratory Distress Syndrome

text: Respiratory viruses are a common cause of severe pneumonia and acute respiratory distress syndrome (ARDS) in adults. The advent of new diagnostic technologies, particularly multiplex reverse transcription polymerase chain reaction, have increased the recognition of viral respiratory infections in critically ill adults. Supportive care for adults with ARDS caused by respiratory viruses is similar to the care of patients with ARDS from other causes. Although antiviral therapy is available for some respiratory viral infections, further research is needed to determine which groups of patients would benefit.


title: Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study

text: BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.


A CALL FOR RAPID SUBMISSION OF DATA FOR AGGREGATE REVIEW: Can daily radiotherapy imaging be used as a potential screen for COVID-19?


title: Respiratory Illness and Allergy Related to Work and Home Environment among Commercial Pilots

text: The aim was to study associations between work and home environment and prevalence and incidence of respiratory health and a history of atopy in a 3-y cohort of commercial pilots. A questionnaire was mailed in 1997 to all pilots in a Scandinavian airline company (N = 622); 577 (93%) participated. The same questionnaire was sent to the participants 3 years later, 436 participated (76%). There were questions on asthma, respiratory symptoms and infections, allergies, the cabin environment, psychosocial environment and the home environment. Associations were analyzed by multiple logistic regression, calculating odds ratios (OR) with 95% confidence intervals (95%CI). The incidence of doctors’ diagnosed asthma and atopy were 2.4 and 16.6 per 1000 person years, respectively. Pilots changing type of flight during follow-up got more airway infections (OR = 11.27; 95% CI 2.39–53.14). Those reporting decreased work control (OR = 1.85; 95% CI 1.03–3.31 for 1 unit change) and those with environmental tobacco smoke (ETS) at home (OR = 3.73; 95% CI 1.09–12.83) had a higher incidence of atopy during follow up. Dampness or mould at home was associated with a higher prevalence of asthma symptoms (OR = 3.55; 95% CI 1.43–8.82) and airway infections (OR = 3.12 95% CI 1.27–7.68). Window pane condensation in winter at home, reported at baseline, was associated with increased incidence of asthma symptoms (OR = 4.14; 95% CI 1.32–12.97) and pilots living in newer buildings at baseline had a higher incidence of airway infections (OR = 5.23; 95% CI 1.43–19.10). In conclusion, lack of work control and ETS at home can be a risk factors for development of allergic symptoms in pilots. Window pane condensation at home can be a risk factor for incidence of asthma symptoms. Dampness and mould at home can be a risk factor for prevalence of asthma symptoms and airway infections and living in newer buildings can be a risk factor for incidence of airway infections.


title: Monitoring Transmissibility and Mortality of COVID-19 in Europe

text: Abstract Objectives As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective was to report real-time effective reproduction numbers (R(t)) case fatality rate (CFR). Methods Data were mainly obtained from WHO website, up to 9 March 2020. R(t) was estimated by exponential growth rate (EG) and time dependent (TD) methods. “R0” package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both naïve CFR (nCFR) and adjust CFR (aCFR) were estimated. Results In EG method, R(t) was 3.27 [3.17-3.38] for Italy, 6.32 [5.72-6.99] for France, 6.07 [5.51-6.69] for Germany, 5.08 [4.51-5.74] for Spain. With TD method, the R value for March 9 was 3.10 [2.21-4.11] for Italy, 6.56 [2.04-12.26] for France, 4.43 [1.83-7.92] for Germany, and 3.95 [0-10.19] for Spain. Conclusions This study provides important findings on an early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority


title: Conceptualising COVID-19’s impacts on household food security

text: COVID-19 undermines food security both directly, by disrupting food systems, and indirectly, through the impacts of lockdowns on household incomes and physical access to food. COVID-19 and responses to the pandemic could undermine food production, processing and marketing, but the most concerning impacts are on the demand-side – economic and physical access to food. This paper identifies three complementary frameworks that can contribute to understanding these effects, which are expected to persist into the post-pandemic phase, after lockdowns are lifted. FAO’s ‘four pillars’– availability, access, stability and utilisation – and the ‘food systems’ approach both provide holistic frameworks for analysing food security. Sen’s ‘entitlement’ approach is useful for disaggregating demand-side effects on household production-, labour-, trade- and transfer-based entitlements to food. Drawing on the strengths of each of these frameworks can enhance the understanding of the pandemic’s impacts on food security, while also pinpointing areas for governments and other actors to intervene in the food system, to protect the food security of households left vulnerable by COVID-19 and public responses.


title: Pandemics and the great evolutionary mismatch

text: Dezecache et al. argue that affiliation and contact-seeking are key responses to danger. These natural social tendencies are likely to hinder the observance of physical distancing during the current pandemic. We need internet access at this time, not only to promote freedom of expression, but also to promote public health.


title: Guide to Selection of Fluoroquinolones in Patients with Lower Respiratory Tract Infections

text: Newer fluoroquinolones such as levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin have several attributes that make them excellent choices for the therapy of lower respiratory tract infections. In particular, they have excellent intrinsic activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and the atypical respiratory pathogens. Fluoroquinolones may be used as monotherapy to treat high-risk patients with acute exacerbation of chronic bronchitis, and for patients with community-acquired pneumonia requiring hospitalisation, but not admission to intensive care. Overall, the newer fluoroquinolones often achieve clinical cure rates in ≥90% of these patients. However, rates may be lower in hospital-acquired pneumonia, and this infection should be treated on the basis of anticipated organisms and evaluation of risk factors for specific pathogens such as Pseudomonas aeruginosa. In this setting, an antipseudomonal fluoroquinolone may be used in combination with an antipseu-domonal β-lactam. Concerns are now being raised about the widespread use, and possibly misuse, of fluoroquinolones and the emergence of resistance among S. pneumoniae, Enterobacteriaceae and P. aeruginosa. A number of pharmacokinetic parameters such as the peak concentration of the antibacterial after a dose (C(max)), and the 24-hour area under the concentration-time curve (AUC(24)) and their relationship to pharmacodynamic parameters such as the minimum inhibitory and the mutant prevention concentrations (MIC and MPC, respectively) have been proposed to predict the effect of fluoroquinolones on bacterial killing and the emergence of resistance. Higher C(max)/MIC or AUC(24)/MIC and C(max)/MPC or AUC(24)/MPC ratios, either as a result of dose administration or the susceptibility of the organism, may lead to a better clinical outcome and decrease the emergence of resistance, respectively. Pharmacokinetic profiles that are optimised to target low-level resistant minor subpopulations of bacteria that often exist in infections may help preserve fluoroquinolones as a class. To this end, optimising the AUC24/ MPC or Cmax/MPC ratios is important, particularly against S. pneumoniae, in the setting of lower respiratory tract infections. Agents such as moxifloxacin and gemifloxacin with high ratios against this organism are preferred, and agents such as ciprofloxacin with low ratios should be avoided. For agents such as levofloxacin and gatifloxacin, with intermediate ratios against S. pneumoniae, it may be worthwhile considering alternative dose administration strategies, such as using higher dosages, to eradicate low-level resistant variants. This must, of course, be balanced against the potential of toxicity. Innovative approaches to the use of fluoroquinolones are worth testing in further in vitro experiments as well as in clinical trials.


title: Modelling the Epidemiology of Infectious Diseases for Decision Analysis: A Primer

text: The number of economic evaluations related to infectious disease topics has increased over the last 2 decades. However, many such evaluations rely on models that do not take into account unique features of infectious diseases that can affect the estimated value of interventions against them. These include their transmissibility from infected to susceptible individuals, the possibility of acquiring natural immunity following recovery from infection and the uncertainties that arise as a result of their complex natural history and epidemiology. Modellers conducting economic evaluations of infectious disease interventions need to know the main features of different types of infectious disease models, the situations in which they should be applied and the effects of model choices on the cost effectiveness of interventions.


title: Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction

text: BACKGROUND: Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset. METHODS: Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry. RESULTS: Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls, P < 0.001) and at peak exercise (− 15.8 ± 2.6 vs − 23.4 ± 4.3, P < 0.001). Systolic pulmonary artery pressure (sPAP) and E/E′ ratios increase during effort were higher in OSA than in controls (ΔsPAP 44.3% ± 6.4 vs 32.3% ± 5.5, P < 0.0001, and ΔE/E’ 87.5% ± 3.5 vs 25.4% ± 3.3, P < 0.0001, respectively). The best correlate of E/E′ at peak stress was peak exertion capacity (r = − 0.50, P < 0.001). OB was also increased in OSA patients (P = 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction. CONCLUSIONS: Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.


title: Significance of clinical phenomes of patients with COVID‐19 infection: A learning from 3795 patients in 80 reports

text: A new coronavirus SARS‐CoV‐2 has caused outbreaks in multiple countries and the number of cases is rapidly increasing through human‐to‐human transmission. Clinical phenomes of patients with SARS‐CoV‐2 infection are critical in distinguishing it from other respiratory infections. The extent and characteristics of those phenomes varied depending on the severities of the infection, for example, beginning with fever or a mild cough, progressed with signs of pneumonia, and worsened with severe or even fatal respiratory difficulty in acute respiratory distress syndrome. We summarized clinical phenomes of 3795 patients with COVID‐19 based on 80 published reports from the onset of outbreak to March 2020 to emphasize the importance and specificity of those phenomes in diagnosis and treatment of infection, and evaluate the impact on medical services. The data show that the incidence of male patients was higher than that of females and the level of C‐reaction protein was increased as well as most patients' imaging included ground‐glass opacity. Clinical phenomes of SARS‐CoV‐2 infection were compared with those of SARS‐CoV and MERS‐CoV infections. There is an urgent need to develop an artificial intelligence‐based machine learning capacity to analyze and integrate radiomics‐ or imaging‐based, patient‐based, clinician‐based, and molecular measurements‐based data to fight the outbreak of COVID‐19 and enable more efficient responses to unknown infections in future.


title: Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service

text: BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged ≥ 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587–0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601–0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.


title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway

text: Alternative complement pathway (AP) plays an important role in the development of sepsis, which is life threatening. Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. However, the underlying mechanism of the disease development is largely unknown. There is no report on CFHR1 gene knockout in any animal infection model and its function in vivo is still unclear. Here, a Cfhr1 knockout mouse was generated for investigating AP in sepsis and sepsis-induced acute kidney injury (AKI). We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. This study revealed the function of FHR-E in vivo, which may further provide hints to the pathogenesis of FHR-1 deficiency-related diseases by enhancing LPS-induced AP activation.


title: Tracking virus outbreaks in the 21st century

text: Emerging viruses have the potential to impose substantial mortality, morbidity and economic burdens on human populations. Tracking the spread of infectious diseases to assist in their control has traditionally relied on the analysis of case data gathered as the outbreak proceeds. Here, we describe how many of the key questions in infectious disease epidemiology, from the initial detection and characterization of outbreak viruses, to transmission chain tracking and outbreak mapping, can now be much more accurately addressed using recent advances in virus sequencing and phylogenetics. We highlight the utility of this approach with the hypothetical outbreak of an unknown pathogen, ‘Disease X’, suggested by the World Health Organization to be a potential cause of a future major epidemic. We also outline the requirements and challenges, including the need for flexible platforms that generate sequence data in real-time, and for these data to be shared as widely and openly as possible.


title: COVID-19 and healthcare lessons already learned

text: COVID-19 has exposed deep-rooted flaws in our health system regarding healthcare financing and delivery. This essay uses COVID-19 as a frame to reflect on the growth in our uninsured population, the flaws inherent in healthcare federalism, how “Trumpcare” has made things worse, the magnified importance of Medicaid, and the problems inherent in relying primarily on private actors.


title: “Masking” our emotions: Botulinum toxin, facial expression, and well‐being in the age of COVID‐19

text: BACKGROUND: The globally devastating effects of COVID‐19 breach not only the realm of public health, but of psychosocial interaction and communication as well, particularly with the advent of mask‐wearing. METHODS: A review of the literature and understanding of facial anatomy and expressions as well as the effect of botulinum toxin on emotions and nonverbal communication. RESULTS: Today, the mask has become a semi‐permanent accessory to the face, blocking our ability to express and perceive each other’s facial expressions by dividing it into a visible top half and invisible bottom half. This significantly restricts our ability to accurately interpret emotions based on facial expressions and strengthens our perceptions of negative emotions produced by frowning. The addition of botulinum toxin (BTX)–induced facial muscle paralysis to target the muscles of the top (visible) half of the face, especially the corrugator and procerus muscles, may act as a therapeutic solution by its suppression of glabellar lines and our ability to frown. The treatment of the glabella complex not only has been shown to inhibit the negative emotions of the treated individual but also can reduce the negative emotions in those who come in contact with the treated individual. CONCLUSIONS: Mask‐wearing in the wake of COVID‐19 brings new challenges to our ability to communicate and perceive emotion through full facial expression, our most effective and universally shared form of communication, and BTX may offer a positive solution to decrease negative emotions and promote well‐being for both the mask‐wearer and all who come in contact with that individual.


title: Activation of toll-like receptor signaling pathway for protection against influenza virus infection

text: This study aims to evaluate the antiviral role of nucleic acid-based agonists for the activation of toll-like receptor (TLR) signaling pathways, and its protective role in respiratory influenza A virus infections. TLR-3 is expressed on myeloid dendritic cells, respiratory epithelium, and macrophages, and appears to play a central role in mediating both the antiviral and inflammatory responses of the innate immunity in combating viral infections. Influenza viruses can effectively inhibit the host's ability to produce interferons, and thereby suppress the immune system's antiviral defence mechanisms. Poly ICLC is a synthetic double stranded RNA comprising of polyriboinosinic-poly ribocytidylic acid (Poly IC) stabilized with l-lysine (L) and carboxymethylcellulose (C). Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) are TLR-3 agonists and are potent inducer of interferons and natural killer cells. Intranasal pre-treatment of mice with Poly ICLC and LE Poly ICLC provided high level of protection against lethal challenge with a highly lethal avian H5N1 influenza (HPAI) strain (A/H5N1/chicken/Henan clade 2), and against lethal seasonal influenza A/PR/8/34 [H1N1] and A/Aichi/2 [H3N2] virus strains. The duration of protective antiviral immunity to multiple lethal doses of influenza virus A/PR/8/34 virus had been previously found to persist for up to 3 weeks in mice for LE Poly ICLC and 2 weeks for Poly ICLC. Similarly, pre-treatment of mice with CpG oligonucleotides (TLR-9 agonist) was also found to provide complete protection against influenza A/PR/8/34 infection in mice. RT-PCR analysis of lung tissues of mice treated with Poly ICLC and LE Poly ICLC revealed upregulation of TLR-3 mRNAs gene expression. Taken together, these results do support the potential role of TLR-3 and TLR-9 agonists such as Poly ICLC and LE Poly ICLC in protection against lethal seasonal and HPAI virus infection.


title: Peptide nucleic acids: Advanced tools for biomedical applications

text: Abstract Peptide Nucleic Acids (PNAs) are the DNA/RNA analogues in which sugar-phosphate backbone is replaced by N-2-aminoethylglycine repeating units. PNA contains neutral backbone hence due to the absence of electrostatic repulsion, its hybridization shows remarkable stability towards complementary oligonucleotides. PNAs are highly resistant to cleavage by chemicals and enzymes due to the substrate specific nature of enzymes and therefore not degraded inside the cells. PNAs are emerging as new tools in the market due to their applications in antisense and antigene therapies by inhibiting translation and transcription respectively. Hence, several methods based on PNAs have been developed for designing various anticancer and antigene drugs, detection of mutations or modulation of PCR reactions. The duplex homopurine sequence of DNA may also be recognized by PNA, forming firm PNA/DNA/PNA triplex through strand invasion with a looped-out DNA strand. PNAs have also been found to replace DNA probes in varied investigative purposes. There are several disadvantages regarding cellular uptake of PNA, so modifications in PNA backbone or covalent coupling with cell penetrating peptides is necessary to improve its delivery inside the cells. In this review, hybridization properties along with potential applications of PNA in the field of diagnostics and pharmaceuticals are elaborated.


title: Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19

text: Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.


title: Lessons from the COVID-19 pandemic – will virtual patient management reshape uro-oncology in Germany?

text: Abstract The Coronavirus disease (COVID-19) pandemic is challenging for physicians treating patients with genitourinary cancers as those are considered at high risk for severe events. The uro-oncology outpatient clinic at our academic institution was affected early by the outbreak due to the widespread infection of health care personnel. Subsequently, we developed a strategy to ensure patient’s safety by efforts focused on strict quarantine observation, reduction of clinic visits and implementation of virtual patient management into the workflow. Further, we analyze susceptibility to COVID-19 and its effects on uro-oncological patients treated with anti-tumoral agents. The goal is to warrant high quality cancer care, despite being an academic center on the front-line of Germany’s response to COVID-19.


title: Hypothesis for the management and treatment of the COVID-19-induced acute respiratory distress syndrome and lung injury using mesenchymal stem cell-derived exosomes

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronaviridae that causes respiratory disorders. After infection, large amounts of inflammatory cytokines are secreted, known as the cytokine storm. These cytokines can cause pulmonary damage induced by inflammation resulting in acute respiratory distress syndrome (ARDS), and even death. One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. But our suggestion is using MSCs-derived exosomes. Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don’t have problems associated to cell maintenance and injections. For investigation the hypothesis, MSCs should be isolated from tissues and characterized. Then, the exosomes should be isolated from the supernatants and characterized. These exosomes should be injected into a transgenic animal for COVID-19. In the final section, lung function assessment, histological examination, micro-CT, differential leukocyte, viral load analysis, cytokine assay, and CRP level analysis can be investigated. COVID-19 treatment is currently focused on supportive therapies and no vaccine has not been developed for it, so, numerous research studies are needed to find potential. Since the pathogenesis of this disease was identified in previous studies and can cause lung injury with ARDS, so, investigation of the therapeutic approaches that can suppress inflammation, cytokine storm and ARDS can be helpful in finding a novel therapeutic approach for this disease.


Coronavirus and Obesity: Could Insulin Resistance Mediate the Severity of Covid-19 Infection?


title: Observations about sexual and other routes of SARS‐CoV‐2 (COVID‐19) transmission and its prevention

text: Sexual contact has been proposed as a route of transmission for the SARS-CoV-2 virus, which raises the question of alternate routes of transmission.


title: Establishment of a Virulent Full-Length cDNA Clone for Type I Feline Coronavirus Strain C3663

text: Feline infectious peritonitis (FIP) is one of the most important infectious diseases in cats and is caused by feline coronavirus (FCoV). Tissue culture-adapted type I FCoV shows reduced FIP induction in experimental infections, which complicates the understanding of FIP pathogenesis caused by type I FCoV. We previously found that the type I FCoV strain C3663 efficiently induces FIP in specific-pathogen-free cats through the naturally infectious route. In this study, we employed a bacterial artificial chromosome-based reverse genetics system to gain more insights into FIP caused by the C3633 strain. We successfully generated recombinant virus (rC3663) from Fcwf-4 cells transfected with infectious cDNA that showed growth kinetics similar to those shown by the parental virus. Next, we constructed a reporter C3663 virus carrying the nanoluciferase (Nluc) gene to measure viral replication with high sensitivity. The inhibitory effects of different compounds against rC3663-Nluc could be measured within 24 h postinfection. Furthermore, we found that A72 cells derived from canine fibroblasts permitted FCoV replication without apparent cytopathic effects. Thus, our reporter virus is useful for uncovering the infectivity of type I FCoV in different cell lines, including canine-derived cells. Surprisingly, we uncovered aberrant viral RNA transcription of rC3663 in A72 cells. Overall, we succeeded in obtaining infectious cDNA clones derived from type I FCoV that retained its virulence. Our recombinant FCoVs are powerful tools for increasing our understanding of the viral life cycle and pathogenesis of FIP-inducing type I FCoV. IMPORTANCE Feline coronavirus (FCoV) is one of the most significant coronaviruses, because this virus induces feline infectious peritonitis (FIP), which is a lethal disease in cats. Tissue culture-adapted type I FCoV often loses pathogenicity, which complicates research on type I FCoV-induced feline infectious peritonitis (FIP). Since we previously found that type I FCoV strain C3663 efficiently induces FIP in specific-pathogen-free cats, we established a reverse genetics system for the C3663 strain to obtain recombinant viruses in the present study. By using a reporter C3663 virus, we were able to examine the inhibitory effect of 68 compounds on C3663 replication in Fcwf-4 cells and infectivity in a canine-derived cell line. Interestingly, one canine cell line, A72, permitted FCoV replication but with low efficiency and aberrant viral gene expression.


title: Influenza virus A(H1N1)pdm09 hemagglutinin polymorphism and associated disease in southern Germany during the 2010/11 influenza season

text: A novel influenza A virus emerged in early 2009 to cause the first influenza pandemic of the 21(st) century. Understanding the evolution of influenza virus is crucial to determine pathogenesis, vaccine efficacy, and resistance to antiviral drugs. In this study, we investigated the molecular evolution of influenza virus A(H1N1)pdm09 in the 2010/11 influenza season in southern Germany by sequence analysis of the influenza virus hemagglutinin gene from 25 patients with mild, moderate, and severe disease. Phylogenetic analysis revealed co-circulation of different genetic groups. The D222G mutation, which had previously been observed in severe cases, was not detected. Immunocompromised patients were not affected more severely than non-immunocompromised patients (p>0.05), although longer shedding was observed in some of them. Interestingly, additional mutations and potential glycosylation sites were detected in samples from the lower respiratory tract in two patients, but not in the corresponding upper respiratory tract specimens. The H275Y mutation in the influenza virus neuraminidase gene, known to confer resistance to the neuraminidase inhibitor oseltamivir, was detected in one patient.


title: Characterization of the Complete Genome of Chikungunya in Zhejiang, China, Using a Modified Virus Discovery Method Based on cDNA-AFLP

text: BACKGROUND: Chikungunya (CHIK) virus is a mosquito-borne emerging pathogen presenting great health challenges worldwide, particularly in tropical zones. Here we report a newly detected strain of CHIK, Zhejiang/chik-sy/2012, in China, a nonindigenous region for CHIK, using a modified approach based on the classic cDNA-AFLP. We then performed etiological and phylogenetic analyses to better understand its molecular characterization and phylogenetic pattern, and also to aid in further evaluating its persistence in Southeast Asia. METHODS: By using this modified procedure, we determined for the first time the complete genome sequence of the chikungunya virus strain, Zhejiang/chik-sy/2012, isolated in 2012 from a patient in Zhejiang, China. Sequence analyses revealed that this positive single strand of RNA is 12,017 bp long. We found no single amino acid mutation in A226V, D284E and A316V. Phylogenetic analysis showed that our strain shared the greatest homology with a strain isolated in Taiwan, which was derived from a strain from Indonesia. Chik-sy/2012 is in a different clade from other CHIK viruses found in China previously. CONCLUSIONS: A modified cDNA-AFLP in virus discovery was used to isolate the first CHIK and the first complete genome sequence of virus strain chik-sy/2012 in 2012 from a patient with CHIK fever in Zhejiang, China. The infection displayed great phylogenetic distance from viruses detected in Guangdong, China, in 2008 and 2010, since they were derived from another evolutionary lineage. Additional molecular epidemiology data are needed to further understand, monitor and evaluate CHIK in China.


title: 89 Severe Acute Respiratory Syndrome (SARS)

text: Abstract Severe acute respiratory syndrome (SARS) first appeared in November 2002 and ultimately resulted in 8096 probable human infections and 774 deaths worldwide. By July 2003, the global outbreak was declared over. A new coronavirus, SARS-associated coronavirus (SARS-CoV), was identified as the causative agent; this virus appeared to have a zoonotic origin, as genetically similar coronaviruses have been identified in several animal species. The global response to the outbreak was extensive. Within a short period, the pathogen had been identified, new diagnostic tests were developed, surveillance systems were created, infection control and prevention measures were instituted, and transmission among humans stopped. It is unclear if and when person-to-person SARS-CoV transmission will reappear. However, procedures have been established by public health organizations, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), to help guide diagnosis, reporting, surveillance, and prevention.


title: Automated collection of pathogen-specific diagnostic data for real-time syndromic epidemiological studies

text: Health-care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are pathogen-specific. We describe a system, FilmArray® Trend, for rapid disease reporting that is syndrome-based but pathogen-specific. Results from a multiplex molecular diagnostic test are sent directly to a cloud database. www.syndromictrends.com presents these data in near real-time. Trend preserves patient privacy by removing or obfuscating patient identifiers. We summarize the respiratory pathogen results, for 20 organisms from 344,000 patient samples acquired as standard of care testing over the last four years from 20 clinical laboratories in the United States. The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks and adenovirus and bacterial pathogens show constant detection over the year. Interestingly, the rate of pathogen co-detections, on average 7.7%, matches predictions based on the relative abundance of organisms present.


title: Infection Control Precautions and Care Delivery in Hemodialysis Unit during Coronavirus Disease 2019 Outbreak: A Case Series

text: BACKGROUND: With an estimated basic reproductive number of 3.77, the Coronavirus Disease 2019 (COVID-19) continues to spread. It is urgent to exert adequate efforts for the management of dialysis patients, caregivers, and healthcare personnel (HCP). This study aimed at reporting practical workflow, identification of high-risk or suspected cases of COVID-19, and subsequent response measures. METHODS: At the time of the COVID-19 outbreak, precautions and practice protocols were applied in our dialysis units (DUs). This single-center study retrospectively reviewed all high-risk/suspected cases from January 23, 2020, to February 10, 2020. Epidemiological, clinical feature, and detailed data on all cases were recorded. RESULTS: Practical workflow for the clinical management of dialysis patients, caregivers, and HCP was initiated. A total of 6 high-risk/suspected cases were identified. Female gender, older age, presence of cardiovascular disease, diabetes, anuresis, immunocompromised status, hypoalbuminemia, and underweight were noticeable features in these cases. Direct evidence of infection or epidemiological risk was detected in five cases. Close monitoring for temperature and oxygen saturation during hemodialysis sessions may be reasonable. No confirmed COVID-19 cases were reported in our DU, but certain cases showed rapid deterioration due to other critically severe condition needing hospitalization. Portable dialysis machines are of great need to ensure dialysis care provision. CONCLUSIONS: Our study described a practical workflow for patient-centered management during COVID-19 outbreak. Potential risk factors and underlying clinical patterns were reported. Further studies regarding the efficacy of infection control precautions and practice protocols tailored for dialysis settings are warranted.


title: Group-specific structural features of the 5′-proximal sequences of coronavirus genomic RNAs

text: Abstract Global predictions of the secondary structure of coronavirus (CoV) 5′ untranslated regions and adjacent coding sequences revealed the presence of conserved structural elements. Stem loops (SL) 1, 2, 4, and 5 were predicted in all CoVs, while the core leader transcription-regulating sequence (L-TRS) forms SL3 in only some CoVs. SL5 in group I and II CoVs, with the exception of group IIa CoVs, is characterized by the presence of a large sequence insertion capable of forming hairpins with the conserved 5′-UUYCGU-3′ loop sequence. Structure probing confirmed the existence of these hairpins in the group I Human coronavirus-229E and the group II Severe acute respiratory syndrome coronavirus (SARS-CoV). In general, the pattern of the 5′ cis-acting elements is highly related to the lineage of CoVs, including features of the conserved hairpins in SL5. The function of these conserved hairpins as a putative packaging signal is discussed.


title: Are identity badges and lanyards in pediatrics potentially contaminated with viral pathogens?

text: Identity (ID) badges and lanyards worn by pediatric health care workers (HCWs) have been shown to be potential vectors of nosocomial bacterial infections. This cross-sectional study determined the contamination of ID badges and lanyards worn by pediatric HCWs with common respiratory and gastrointestinal viruses. The results showed that ID badges and lanyards are not significantly contaminated with common respiratory or gastrointestinal viruses and are unlikely to be a significant vector for nosocomial infection.


Human factors issues of working in personal protective equipment during the COVID‐19 pandemic


title: Human metapneumovirus: review of an important respiratory pathogen

text: Summary Human metapneumovirus (hMPV), discovered in 2001, most commonly causes upper and lower respiratory tract infections in young children, but is also a concern for elderly subjects and immune-compromised patients. hMPV is the major etiological agent responsible for about 5% to 10% of hospitalizations of children suffering from acute respiratory tract infections. hMPV infection can cause severe bronchiolitis and pneumonia in children, and its symptoms are indistinguishable from those caused by human respiratory syncytial virus. Initial infection with hMPV usually occurs during early childhood, but re-infections are common throughout life. Due to the slow growth of the virus in cell culture, molecular methods (such as reverse transcriptase PCR (RT-PCR)) are the preferred diagnostic modality for detecting hMPV. A few vaccine candidates have been shown to be effective in preventing clinical disease, but none are yet commercially available. Our understanding of hMPV has undergone major changes in recent years and in this article we will review the currently available information on the molecular biology and epidemiology of hMPV. We will also review the current therapeutic interventions and strategies being used to control hMPV infection, with an emphasis on possible approaches that could be used to develop an effective vaccine against hMPV.


title: Covid-19: Mann+Hummel supplies HEPA filters for Ford's respirators

text: Mann+Hummel is supporting Ford Motor Co, one of its key automotive customers, on the rapid development and production of powered air purifier respirators.


title: Interleukin‐10 is a critical regulator of white matter lesion containment following viral induced demyelination

text: Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti‐inflammatory cytokine IL‐10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL‐10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL‐10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL‐10 sufficient mice correlated with IL‐10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL‐10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106–2120


title: Effects of COVID‐19 Lockdown on Lifestyle Behaviors in Children with Obesity Living in Verona, Italy: A Longitudinal Study

text: OBJECTIVE: To test the hypothesis that youths with obesity, when removed from structured school activities and confined to their homes during the COVID‐19 pandemic, will display unfavorable trends in lifestyle behaviors. METHODS: The sample included 41 children and adolescents with obesity participating in a longitudinal observational study located in Verona, Italy. Lifestyle information including diet, activity, and sleep behaviors were collected at baseline and three weeks into the national lockdown during which home confinement was mandatory. Changes in outcomes over the two study time points were evaluated for significance using paired t‐tests. RESULTS: There were no changes in reported vegetable intake; fruit intake increased (p=0.055) during the lockdown. By contrast, potato chip, red meat, and sugary drink intakes increased significantly during the lockdown (p‐value range, 0.005 to <0.001). Time spent in sports activities decreased (X±SD) by 2.30±4.60 hours/week (p=0.003) and sleep time increased by 0.65±1.29 hours/day (p=0.003). Screen time increased by 4.85±2.40 hours/day (p<0.001). CONCLUSIONS: Recognizing these adverse collateral effects of the COVID‐19 pandemic lockdown is critical in avoiding depreciation of weight control efforts among youths afflicted with excess adiposity. Depending on duration, these untoward lockdown effects may have a lasting impact on a child’s or adolescent’s adult adiposity level.


title: Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis.

text: Background The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.


Successful Use of Limited Transthoracic Echocardiography to Guide VV ECMO Placement in a COVID-19 Patient


title: Infectious pneumonia in the immunocompetent host: What the radiologist should know

text: Lung infections are an important cause of morbidity and mortality, particularly because of the rising antimicrobial resistance. According to the clinical setting, they can be categorized as community-acquired pneumonia and hospital-acquired pneumonia. Radiological patterns of lung infections are lobar consolidation, bronchopneumonia, interstitial pattern, and nodular pattern. In addition, typical imaging features of several infections serve as “red flag signs” in reaching a diagnosis or altering the management. It would be prudent for the radiologist to be well informed regarding these aspects of lung infections to be able to make a valuable contribution to the management.


title: Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey

text: BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.


title: Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis

text: BACKGROUND: Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission. METHODS: Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured. RESULTS: Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73–0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room. CONCLUSIONS: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.


title: Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV

text: In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibody-based therapeutics by combining two or more functional antigen-recognizing elements into a single construct. However, to the best of our knowledge there has been no reported cases of effective antiviral antibody-peptide bispecific fusion proteins. We previously developed potent fully human monoclonal antibodies and inhibitory peptides against Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a novel coronavirus that causes severe acute respiratory illness with high mortality. Here, we describe the generation of antibody-peptide bispecific fusion proteins, each of which contains an anti-MERS-CoV single-chain antibody m336 (or normal human IgG1 CH3 domain as a control) linked with, or without, a MERS-CoV fusion inhibitory peptide HR2P. We found that one of these fusion proteins, designated as m336 diabody-pep, exhibited more potent inhibitory activity than the antibody or the peptide alone against pseudotyped MERS-CoV infection and MERS-CoV S protein-mediated cell-cell fusion, suggesting its potential to be developed as an effective bispecific immunotherapeutic for clinical use.


The first Sino-German symposium on cancer research, Shanghai May 2007


title: Comparison of FTD® respiratory pathogens 33 and a singleplex CDC assay for the detection of respiratory viruses: A study from Cameroon

text: Abstract Introduction: This study compares the detection of 14 common respiratory viruses by two different real-time reverse transcription polymerase chain reaction (rRT-PCR) methods: in house singleplex tests developed by the Centers for Disease Control and Prevention and the commercially available Fast Track Diagnostic (FTD®) Respiratory Pathogens 33 multiplex test. Methods: A total of 217 nasopharyngeal swabs were analyzed using CDC singleplex rRT-PCR and FTD® Respiratory Pathogens 33 multiplex assays, for the detection of 14 respiratory viruses. Results: The results showed that 179/217 (82.5%) samples were positive with the singleplex method and 183/217 (84.3%) with the FTD® Respiratory Pathogens 33 multiplex test. Excellent or satisfactory agreement was obtained for all viruses (k > 0.6) except Parainfluenzavirus 4 (k = 0.24) and influenza B (k = 0.51). Conclusion: Although the multiplex FTD kits were more expensive than the singleplex assay, the FTD kits yielded rapid results in a shorter timeframe, increasing efficiency of diagnosis.


title: Coronavirus: Short‐term pain but strong rebound likely

text: ▪ Attention has understandably focused on limiting the damage from the short‐term effects of the coronavirus outbreak. But it's likely that, once disruption and uncertainty fade, the rebound in activity will be strong. It's important for firms to position themselves for such a recovery. ▪ Historical evidence supports this view. In the past 200 years, short recessions have typically been followed by robust recovery. Long‐term impacts from natural disasters have generally only been evident for specific hazards. Except for AIDS, longer‐term pandemic effects also appear to have been contained. ▪ Surveys during the 2003 SARS and 2009 influenza outbreaks highlight one explanation for time‐limited impacts. Public fears increased alongside rising infection rates, but they dissipated promptly as outbreaks came under control. ▪ Our modelling is consistent with these stylised facts. In our coronavirus pandemic scenario, global growth grinds to a halt in Q2 2020 but then rebounds to a rapid pace within a year. With much of the initial output loss recovered in a relatively short period of time, long‐term impacts are limited. ▪ But there are risks to this view. The period of disruption could be longer than anticipated, depending on the potential spread and seasonality of COVID‐19 and policy actions to mitigate the fallout. Opinion polls also highlight the potential risk of larger, more persistent effects for some countries. ▪ Moreover, coronavirus‐related weakness and associated financial distress could expose other key vulnerabilities ‐ for example related to deteriorating corporate sector balance sheets and fragile trade relations. These would be expected to have persistent effects on global activity over the coming years.


title: Growth of an RNA Virus in Single Cells Reveals a Broad Fitness Distribution

text: Genetic and environmental factors will influence the growth of an RNA virus, but their relative contributions are challenging to resolve because standard culture methods mask how virus particles interact with individual host cells. Here, single particles of vesicular stomatitis virus, a prototype RNA virus, were used to infect individual BHK cells. Infected cells produced 50 to 8000 progeny virus particles, but these differences were lost upon subsequent culture, suggesting the diversity of yields reflected cell-to-cell differences rather than viral genetic variation. Cells infected at different phases of their cell cycle produced from 1400(early S) to 8700(G(2)M) infectious virus particles, coinciding with the middle-to-upper range of the observed distribution. Fluctuations in virus and cell compositions and noisy gene expression may also contribute to the broad distribution of virus yields. These findings take a step toward quantifying how environmental variation can impact the fitness distribution of a RNA virus.


title: An Ecological Framework for Modeling the Geography of Disease Transmission

text: Ecological niche modeling (ENM) is widely employed in ecology to predict species’ potential geographic distributions in relation to their environmental constraints and is rapidly becoming the gold-standard method for disease risk mapping. However, given the biological complexity of disease systems, the traditional ENM framework requires reevaluation. We provide an overview of the application of ENM to disease systems and propose a theoretical framework based on the biological properties of both hosts and parasites to produce reliable outputs resembling disease system distributions. Additionally, we discuss the differences between biological considerations when implementing ENM for distributional ecology and epidemiology. This new framework will help the field of disease ecology and applications of biogeography in the epidemiology of infectious diseases.


title: Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated

text: Abstract The human coronavirus HCoV-OC43 causes a significant fraction of upper respiratory tract infections. Most coronaviruses show a strong species specificity, although the SARS-Coronavirus crossed species from palm civet cats to infect humans. Similarly, HCoV-OC43, likely a member of the same coronavirus group as SARS-CoV, readily crossed the species barrier as evidenced by its rapid adaptation to the murine brain [McIntosh, K., Becker, W.B., Chanock, R.M., 1967. Growth in suckling-mouse brain of “IBV-like” viruses from patients with upper respiratory tract disease. Proc Natl Acad Sci U.S.A. 58, 2268–73]. Herein, we investigated two consequences of this plasticity in species tropism. First, we showed that HCoV-OC43 was able to infect cells from a large number of mammalian species. Second, we showed that virus that was passed exclusively in suckling mouse brains was highly virulent and caused a uniformly fatal encephalitis in adult mice. The surface glycoprotein is a major virulence factor in most coronavirus infections. We identified three changes in the HCoV-OC43 surface glycoprotein that correlated with enhanced neurovirulence in mice; these were located in the domain of the protein responsible for binding to host cells. These data suggest that some coronaviruses, including HCoV-OC43 and SARS-CoV, readily adapt to growth in cells from heterologous species. This adaptability has facilitated the isolation of HCoV-OC43 viral variants with markedly differing abilities to infect animals and tissue culture cells.


title: Medication adherence to first-line antihypertensive drug class in a large Chinese population

text: Abstract Purpose Suboptimal adherence to antihypertensive agents leads to adverse clinical outcomes. This study aims to evaluate the association between first-line antihypertensive drug class and medication adherence in a large Chinese population. Methods All patients prescribed ≥ one antihypertensive drug in 2001–2003 and 2005 who have paid at least two consecutive clinic visits in the public healthcare system of Hong Kong were included. We excluded patients who have followed-up in the clinics for ≤30days. Interval-based Proportion of Days Covered (PDC) was used to assess medication adherence. All patients were followed-up for up to 5years. Binary logistic regression analysis was used to evaluate the factors associated with optimal adherence, defined as PDC ≥80%. Results From 147,914 eligible patients, 69.2% were adherent to the antihypertensive prescriptions. When compared with angiotensin converting enzyme inhibitors (ACEIs), patients initially prescribed α-blockers (adjusted odds ratio [AOR]=0.234, 95% C.I. 0.215–0.256), β-blockers (AOR=0.447, 95% C.I. 0.420, 0.477), thiazide diuretics (AOR=0.431 95% C.I. 0.399, 0.466) and calcium channel blockers (AOR=0.451, 95% C.I. 0.423, 0.481) were significantly less likely to be drug adherers. Angiotensin receptor blockers (ARBs) and fixed-dose combination therapies were similarly likely to be medication adherent. Older age, male gender, visits in general out-patient clinics, residence in urbanized regions, and the presence of comorbidity were positively associated with optimal drug adherence. Conclusion Patients receiving initial prescriptions of ACEIs, ARB and combination therapy had more favorable adherence profiles than the other major antihypertensive classes in real-life clinical practice.


title: Virtual melanoma checks during a pandemic

text: Healthcare services internationally are experiencing unprecedented strain due to the COVID‐19 pandemic. Governments mandate strict social distancing to reduce the spread of SARS‐CoV‐2 infection, and as a result, people are avoiding health services for less urgent issues. In this crisis, it is important that patients continue to receive preventive and surveillance care without compromising their safety or that of healthcare workers.


title: Hospital-acquired human bocavirus in infants

text: Summary Human bocavirus (HBoV) is a respiratory pathogen that affects young children. We screened 511 nasopharyngeal aspirates for hospital-acquired HBoV from infants hospitalised with respiratory infection from January to December 2008. Among 55 children with HBoV infection, 10 cases were hospital-acquired. Compared with the community-acquired cases, coinfection with other respiratory viruses in these patients was uncommon. HBoV should be considered for inclusion in screening protocols for nosocomial childhood respiratory infections, especially in intensive care units.


Mental Wellbeing of Nursing Staff during the COVID-19 Outbreak: A Cultural Perspective


title: Coronavirus 2019-nCoV: A brief perspective from the front line

text: Abstract A novel coronavirus, designated as 2019-nCoV, hit the central Chinese city of Wuhan in late December 2019, and subsequently spread rapidly to all provinces of China and multiple countries. As of 0:00 am February 9, 2020, a total of 37,287 cases have been confirmed infection of 2019-nCoV in China mainland, and 302 cases have also been cumulatively reported from 24 countries. According to the latest data, a total of 813 deaths occurred in China mainland, with the mortality reaching approximately 2.2%. At present, there is no vaccine or specific drugs for the human coronavirus. Therefore, it is critical to understand the nature of the virus and its clinical characteristics, in order to respond to the 2019-nCoV outbreak. Thus, the present study briefly but comprehensively summarizes the not much but timely reports on the 2019-nCoV.


title: Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity

text: Abstract A relationship between the infecting dose and the risk of disease severity has not been demonstrated for SARS-CoV-2 infection. Here, we report three clusters of individuals that were exposed to diverse inoculi in Madrid and overall developed divrgent clinical forms of COVID-19. Our data support that a greater SARS-CoV-2 inoculi at the time of exposure might determine a higher risk of severe COVID-19.


title: Coronavirus Reverse Genetics by Targeted RNA Recombination

text: Targeted RNA recombination was the first reverse genetics system devised for coronaviruses at a time when it was not clear whether the construction of full-length infectious cDNA clones would become possible. In its current state targeted RNA recombination offers a versatile and powerful method for the site-directed mutagenesis of the downstream third of the coronavirus genome, which encodes all the viral structural proteins. The development of this system is described, with an emphasis on recent improvements, and multiple applications of this technique to the study of coronavirus molecular biology and pathogenesis are reviewed. Additionally, the relative strengths and limitations of targeted RNA recombination and infectious cDNA systems are contrasted.


title: High‐Stakes Remote‐Access Open‐Book Examinations

text: The COVID‐19 pandemic has led to unprecedented challenges in medical school assessments. Final year high‐stakes assessments have classically used closed book examinations (CBEs). Alternative methods of assessment such as open book examinations (OBEs) are emerging but are not routinely used in final year medical school exams. OBEs encourage the use of problem‐solving skills more akin to those used in real‐life. There is currently limited data comparing OBEs with CBEs. A systematic review showed there was insufficient evidence to support the exclusive use of either CBEs or OBEs in assessment, however the studies conducted to date have rarely looked at high‐stakes assessments due to concerns about the validity of OBEs(1).


title: Severe acute respiratory syndrome outbreak promotes a strong sense of professional identity among nursing students

text: This is a phenomenological study that examined nursing students’ perception of nursing professional identity during severe acute respiratory syndrome (SARS) outbreak in Hong Kong in 2003. The aim of the study was to find out how the impact of the SARS event might have affected nursing students in identification with the nursing profession. A total of 10 nursing students were interviewed. This study showed that the SARS crisis enhanced a reconstruction of worldview and affirmed the professional identity of nursing students. Central themes derived from the interview were (1) appreciation and sharing of nursing identity; (2) a sense of moral duty; (3) a change of worldview and feeling of self-growth. This study provided insights to nursing education that acquisition of professional identity could be enhanced through reflective appreciation of critical events such as SARS.


title: TLR9 agonists induced cell death in Burkitt's lymphoma cells is variable and influenced by TLR9 polymorphism

text: Toll-like receptor 9 (TLR9) triggering is a promising novel strategy to combat cancer as it induces innate and adaptive immunity responses. B-cell lymphoma is unique in this context as tumor cells express TLR9 and may harbor latent Epstein-Barr virus (EBV), a gamma-herpesvirus with remarkable oncogenic potential when latent. Latent EBV may be promoted by TLR9 triggering via suppression of lytic EBV. Here, we elaborated an initial assessment of the impact of TLR9 triggering on EBV-positive and EBV-negative B-cell lymphoma using Burkitt's lymphoma (BL) cell lines as an in vitro model. We show that, independent of the presence of EBV, the TLR9 ligand oligodeoxynucleotide (ODN) CpG-2006 may or may not induce caspase-dependent cell death in BL cells. Moreover, ODN CpG-2006-induced cell death responses of BL cells were associated with TLR9 single-nucleotide polymorphisms (SNPs) rs5743836 or rs352140, which we detected in primary BL tumors and in peripheral blood from healthy individuals at similar frequencies. Thus, our findings suggest that the effect of TLR9 agonists on BL cells should be tested in vitro before installment of therapy and TLR9 SNPs in BL patients should be determined as potential biological markers for the therapeutic response to treatment targeting innate immunity.


title: Characterization of a continuous feline mammary epithelial cell line susceptible to feline epitheliotropic viruses

text: Abstract Mucosal epithelial cells are the primary targets for many common viral pathogens of cats. Viral infection of epithelia can damage or disrupt the epithelial barrier that protects underlying tissues. In vitro cell culture systems are an effective means to study how viruses infect and disrupt epithelial barriers, however no true continuous or immortalized feline epithelial cell culture lines are available. A continuous cell culture of feline mammary epithelial cells (FMEC UCD-04-2) that forms tight junctions with high transepithelial electrical resistance (>2000Ωcm−1) 3–4 days after reaching confluence was characterized. In addition, it was shown that FMECs are susceptible to infection with feline calicivirus (FCV), feline herpesvirus (FHV-1), feline coronavirus (FeCoV), and feline panleukopenia virus (FPV). These cells will be useful for studies of feline viral disease and for in vitro studies of feline epithelia.


title: Three-color flow cytometry detection of virus-specific CD4+ and CD8+ T cells in the cat

text: Abstract We describe a three-color flow cytometry assay for the detection of virus-specific CD4+ and CD8+ T cells in the cat. The assay is based upon detection of intracellular TNFα using the cross-reactive mAb 6401.1111, raised against the human cytokine. Allophycocyanin-conjugated mAb 6401.1111 specifically stained feline TNFα-producing murine cells and also Staphylococcus aureus Enterotoxin B-stimulated feline T cells, thus providing formal evidence for cross-reactivity. By using the anti-TNFα mAb in combination with PE- and FITC-conjugated mAbs against feline CD4 and CD8, respectively, antiviral CD4+ and CD8+ T cells could be identified in the peripheral blood and in the spleens of feline infectious peritonitis virus-infected cats. Moreover, feline calicivirus (FCV)-specific CD4+ T cells were detected in the spleens of FCV-vaccinated cats. As antigen-presenting cells (APCs), we used immortalized autologous fibroblast cell lines, PBMC or splenocytes. A straightforward protocol, in which splenocyte preparations served both as APCs and effector cells, consistently yielded best results. The assay will permit further studies of the cellular immune responses in cats during natural and experimental viral infections. It will contribute to vaccine development against feline viruses by facilitating the identification of T cell antigens and epitopes, and by allowing the quantitative detection of virus-specific T cells after vaccination. Furthermore, the assay will add to the value of those systems in which viral infections of the cat serve as models for human disease.


title: Relational lockdown and relational trauma* in the time of Coronavirus: a reflection from a UK family therapist

text: Like a meteor hitting the earth’s surface, 41,698* unexpected deaths have shaken, disturbed and saddened the core of our Nation. This reflection considers the consequences of the Coronavirus crisis on the UK with particular reference to the impact on families and on the practice of family therapists. The perspective presented can only be partial because of the fast changing situation and the limited access to alternative perspectives that is available during this period of relational lockdown. The author provides a systemic understanding of what has happened and what is happening.


title: Validation of the safety of MDCK cells as a substrate for the production of a cell-derived influenza vaccine

text: Abstract Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu®); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 1034. Residual MDCK-DNA is ≤10ng per dose and the ß-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production.


title: Polymerase chain reaction–based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion

text: Abstract Objectives: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. Methods: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining ~105 median cell culture infectious doses of HRV with pooled MEE at 37°C and assaying serial samples for 12 weeks. Results: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. Conclusions: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection. (J Pediatr 1998;133:390-4)


title: Serological Detection of Causative Agents of Infectious and Invasive Diseases in the Beluga Whale Delphinapterus leucas (Pallas, 1776) (Cetacea: Monodontidae) from Sakhalinsky Bay

text: Serological detection of some pathogens in the beluga whale Delphinapterus leucas population from Sakhalinsky Bay of the Sea of Okhotsk (Sakhalin–Amur beluga whale stock) was performed in 2013–2014 after the largest recorded flood of the Amur River (among observations since 1896). The percent of this population that is immune to the causative agents of clonorchosis was 25.6%; toxoplasmosis, 11.5%; brucellosis, 38.5%; tuberculosis, 30.8%; cetacean morbillivirus infection, 16.7%; and to alpha and gamma herpes viruses each, 21.8%.


title: LA PSIQUIATRÍA EN LAS SECUELAS DE COVID-19

text: Resumen La pandemia por Covid-19 ha obligado a modificar sustancialmente la forma de trabajar de los profesionales de la salud mental y puede tener un impacto diferido sobre los pacientes. La Psiquiatría post-Covid-19 pondrá en valor la especialidad como parte de la medicina, los aspectos psicológicos de la práctica médica, la psiquiatría de enlace e interconsulta hospitalaria, la atención domiciliaria, y la atención ambulatoria virtual o telemática. Las consecuencias del confinamiento poblacional, el duelo por las muertes solitarias, y el impacto de la crisis sanitaria sobre los profesionales de la salud mental, desde los dispositivos hospitalarios hasta los comunitarios, de rehabilitación, y la atención primaria, centrarán nuestros esfuerzos durante el desescalado y el medio plazo. Es previsible un aumento de la demanda de atención psiquiátrica a medio y largo plazo y un impacto en la docencia e investigación en salud mental. Abstract The COVID-19 pandemic has forced mental health professionals to substantially change the way they work and may have a delayed impact on patients. The aftermath of COVID-19 will shine a light on certain aspects of psychiatry addressed in this article: psychiatry as a medical specialty, the psychological aspects of medical practice, liaison and consultative psychiatry, home hospitalization, and virtual or telemedicine outpatient care. The consequences of population lockdown, complicated grief over solitary deaths, and the impact of the health crisis on mental health professionals – from hospitals to community services, rehabilitation facilities, and primary care – will be the focus of our efforts during the period of lockdown easing and in the medium term. There will be a foreseeable increase in demand for psychiatric care in the medium and long term along with an impact on mental health education and research.


title: Translating IL-6 biology into effective treatments

text: In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases.


title: Intensive care during the 2019-coronavirus epidemic

text: Abstract On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new coronavirus of 2019 (SARS-CoV-2). SARS-CoV-2 has presented rapid person-to-person transmission and is currently a global pandemic. In the largest number of cases described to date of hospitalized patients with SARS-CoV-2 disease (2019-nCoViD), 26% required care in an intensive care unit (ICU). This pandemic is causing an unprecedented mobilization of the scientific community, which has been associated with an exponentially growing number of publications in relation to it. This narrative literature review aims to gather the main contributions in the area of intensive care to date in relation to the epidemiology, clinic, diagnosis and management of 2019-nCoViD.


title: Diversity of respiratory viruses detected among hospitalized children with acute lower respiratory tract infections at Hospital Serdang, Malaysia

text: Abstract Background The role of respiratory viruses as the major cause of acute lower respiratory tract infections (ALRTIs) in children is becoming increasingly evident due to the use of sensitive molecular detection methods. The aim of this study was to use conventional and molecular detection methods to assess the epidemiology of respiratory viral infections in children less than five years of age that were hospitalized with ALRTIs. Methods The cross-sectional study was designed to investigate the occurrence of respiratory viruses including respiratory syncytisl virus (RSV), human metapneumovirus (HMPV), influenza virus A and B (IFV-A and B), parainfluenzavirus 1, 2, 3 and 4 (PIV 1, 2, 3 and 4), human rhinoviruses (HRV), human enterovirus (HEV), human coronaviruses (HCoV) 229E and OC43, human bocavirus (HBoV) and human adenovirus (HAdV) in hospitalized children with ALRTIs, at Hospital Serdang, Malaysia, from June 16 to December 21, 2009. The study was also designed in part to assess the performance of the conventional methods against molecular methods. Results Viral pathogens were detected in 158 (95.8%) of the patients. Single virus infections were detected in 114 (67.9%) patients; 46 (27.9%) were co-infected with different viruses including double-virus infections in 37 (22.4%) and triple-virus infections in 9 (5.5%) cases. Approximately 70% of samples were found to be positive using conventional methods compared with 96% using molecular methods. A wide range of respiratory viruses were detected in the study. There was a high prevalence of RSV (50.3%) infections, particularly group B viruses. Other etiological agents including HAdV, HMPV, IFV-A, PIV 1–3, HBoV, HCoV-OC43 and HEV were detected in 14.5, 9.6, 9.1, 4.8, 3.6, 2.4 and 1.8 percent of the samples, respectively. Conclusion Our results demonstrated the increased sensitivity of molecular detection methods compared with conventional methods for the diagnosis of ARTIs in hospitalized children. This is the first report of HMPV infections in Malaysia.


Using Serology with Models to clarify the trajectory of the SARS-CoV-2 emerging outbreak


title: Dose tapering for ciclosporin in cats with nonflea‐induced hypersensitivity dermatitis

text: BACKGROUND: Little information is available on the ciclosporin dose‐tapering regimen and clinical response in the treatment of feline hypersensitivity dermatitis. HYPOTHESIS/OBJECTIVES: To test a dose‐tapering regimen and assess efficacy and clinical safety for up to 18 weeks. ANIMALS: Eighty‐eight client‐owned cats with feline hypersensitivity dermatitis. METHODS: Cats that received either a placebo or ciclosporin at 2.5 mg/kg or 7 mg/kg daily for 6 weeks were given 7 mg/kg ciclosporin daily for 4 weeks. Depending on the clinical response, the dose was tapered from daily to every other day over the next 4 weeks and further to twice a week for an additional 4 weeks. RESULTS: After all cats received 7 mg/kg for 4 weeks, the dose could be tapered to every other day for the next 4 weeks in 70% of cats remaining in the study. During the next 4 weeks, 57, 15 and 22% of cats remaining in the study could be treated at twice a week, every other day or daily, respectively. After the first 4 weeks, the mean lesion score and owner‐assessed pruritus improved over baseline by 69 and 61%, respectively, and remained stable during the following 8 weeks. Approximately 65% of the cats in the study were reported to have an adverse event (AE), very often mild and resolving spontaneously. The most frequent AEs were gastrointestinal and included primarily vomiting and diarrhoea. Eighty per cent of AEs occurred when cats were on daily treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that the induction dose of 7 mg/kg ciclosporin can be tapered as soon as 4 weeks without deterioration of the clinical response. Establishment of the lowest effective dosing regimen of ciclosporin reduced the frequency of AEs.


Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study


title: Pneumonies virales acquises sous ventilation mécanique

text: Viral infections (especially respiratory infections) are not rare in critically ill non-immunocompromised patients. Efficient and rapid virologic diagnosis tests such as polymerase chain reaction (PCR) are now widely available. Herpesviridae (herpes simplex virus and cytomegalovirus) are the most frequent viruses detected among non-immunocompromised patients admitted to the intensive care unit (ICU). However, causal relationships between detected viruses and outcomes are still debated, with a variable level of demonstration among the different viruses. The aim of this review was to assess the role of viruses in causing mechanical ventilation-acquired pneumonias in non-immunocompromised ICU adult patients. We also discuss the possible physiopathology of these viral infections, as well as the opportunity for therapeutic interventions.


title: Removal and retention of viral aerosols by a novel alumina nanofiber filter

text: Nanomaterial, due to its unique physical, chemical and biological properties compared to its bulk counterparts, has the potential to provide a product superior to its bulk predecessor. In this study, a novel alumina nanofiber filter was assessed for its removal and retention capability for MS2 aerosol. Its physical removal efficiency in the 10–400nm range was 94.35%, while its viable removal efficiency was 98.87%, which was slightly lower than three conventional HEPA filters tested. However, its pressure drop was much lower than HEPA filters, yielding a higher filter quality than HEPA filters. The average extracted fraction from the nanofiber filter was 8.64×10−2±7.00×10−2, which is three orders lower than other HEPA filters, demonstrating that the viruses were effectively retained in the nanofiber filter. Furthermore, the performance of the nanofiber filter showed no dependence on relative humidity. In conclusion, this novel alumina nanofiber filter presents advantageous potential for removal and retention of viral aerosol agents.


title: Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection

text: In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children’s stool for more than 4 weeks.


title: The viral storm: the dawn of a new pandemic age Nathan Wolfe

text: Unknown


title: Prednisolone reduces recurrent wheezing after first rhinovirus wheeze: a 7‐year follow‐up

text: BACKGROUND: To better understand the role of human rhinovirus‐associated wheeze as a risk factor for childhood recurrent wheezing, a cohort of young children experiencing their first wheezing episode was followed until school age. METHODS: All 111 hospitalized wheezing children (median age, 12 months) were initially participated in a randomized, double‐blind, placebo‐controlled, parallel trial on the efficacy of oral prednisolone. In this 7‐yr follow‐up, risk factors for recurrent wheezing were analysed, and then, the efficacy of prednisolone was evaluated overall and in pre‐specified subgroups post‐hoc. The main outcome was time to recurrent wheezing. RESULTS: The strongest independent risk factor for recurrent wheezing was rhinovirus detection (hazard ratio 3.54; 95% confidence interval 1.51–8.30) followed by sensitization (3.47; 1.55–8.30, respectively) age <1 yr (2.45; 1.29–4.65) and eczema (2.33; 1.11–4.90). Overall, prednisolone did not prevent recurrent wheezing. In subgroup analysis, prednisolone was associated with less recurrent wheezing in children affected by rhinovirus (0.32; 0.12–0.90, adjusted to sensitization, young age, viral aetiology and parental asthma) and/or with eczema (0.27; 0.08–0.87, adjusted respectively). CONCLUSIONS: Our data strengthen the role of rhinovirus‐associated wheeze as an important risk factor for recurrent wheezing and asthma in young first‐time wheezing children. Prospective randomized trials on the efficacy of corticosteroids in rhinovirus‐associated early wheezing are warranted. (ClinicalTrials.gov number, NCT 00494624)


title: Novel Coronavirus Disease (COVID-19) Mitigation Steps Provide a Blueprint for Malaria Control and Elimination

text: Most countries around the world have responded promptly to the novel coronavirus disease (COVID-19) challenge by adopting considered and scientifically guided strategies for its containment. However, the situation is more complex for nations where malaria is endemic, as they now have the additional burden of COVID-19. In such nations, the healthcare systems are either in the preparatory or containment phase of the current pandemic. This enforced, sudden, and sharp public health refocus is likely to result in the disruption of annual malaria control activities such as distribution of insecticide-impregnated bed nets, indoor residual spraying of insecticide, maintenance of malaria surveillance, and mass provision of antimalarial drugs. Nonetheless, we feel that the best facets of COVID-19 public health management can become new guiding principles in malaria-endemic countries to improve malaria control and hasten malaria elimination. Redirection against malaria of the best public health initiatives used in COVID-19 containment could fast-track the global goal of a malaria-free world. Such public health advancement could be one positive outcome from the scourge of COVID-19.


New virus diseases: visible evolution: “…descent with modification”… Charles Darwin