title: Health care facility and community strategies for patient care surge capacity()()

text: Recent terrorist and epidemic events have underscored the potential for disasters to generate large numbers of casualties. Few surplus resources to accommodate these casualties exist in our current health care system. Plans for “surge capacity” must thus be made to accommodate a large number of patients. Surge planning should allow activation of multiple levels of capacity from the health care facility level to the federal level. Plans should be scalable and flexible to cope with the many types and varied timelines of disasters. Incident management systems and cooperative planning processes will facilitate maximal use of available resources. However, resource limitations may require implementation of triage strategies. Facility-based or “surge in place” solutions maximize health care facility capacity for patients during a disaster. When these resources are exceeded, community-based solutions, including the establishment of off-site hospital facilities, may be implemented. Selection criteria, logistics, and staffing of off-site care facilities is complex, and sample solutions from the United States, including use of local convention centers, prepackaged trailers, and state mental health and detention facilities, are reviewed. Proper pre-event planning and mechanisms for resource coordination are critical to the success of a response.


title: Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity

text: Abstract Actinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis - cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulated caspase-1 and its two activators: IFI16 and NLRP1, however, caspase-1 activation was not detected. A549 cells may have been primed for pyroptosis, with the absence of a crucial trigger. The investigation of additional innate immunity elements revealed that A + N (or camptothecin) stimulated the expression of NLRX1, STING (stimulator of interferon genes) and two antiviral proteins, IFIT1 and IFIT3. IFI16 and caspase-1 are coded by p53-regulated genes which led us to investigate regulation of NLRP1, NLRX1, STING, IFIT1 and IFIT3 in p53-dependent mode. The upregulation of NLRP1, NLRX1 and STING was attenuated in p53 knockdown cells. The upsurge of the examined genes, and activation of p53, was inhibited by C16, an inhibitor of PKR kinase. PKR was tested due to its ability to phosphorylate p53 on Ser392. Surprisingly, C16 was active even in PKR knockdown cells. The ability of C16 to prevent activation of p53 and expression of innate immunity genes may be the source of its strong anti-inflammatory action. Moreover, cells exposed to A + N can influence neighboring cells in paracrine fashion, for instance, they shed ectodomain of COL17A1 protein and induce, in p53-dependent mode, the expression of gene for interleukin-7. Further, the activation of p53 also spurred the expression of SOCS1, an inhibitor of interferon triggered STAT1-dependent signaling. We conclude that, stimulation of p53 primes cells for the production of interferons (through upregulation of STING), and may activate negative-feedback within this signaling system by enhancing the production of SOCS1.


title: Prolonged fecal shedding of SARS-CoV-2 in pediatric patients. A quantitative evidence synthesis

text: OBJECTIVE: To investigate differences in viral shedding in respiratory and fecal samples from children with COVID-19. METHODS: We searched PubMed, SCOPUS, Embase and Web of Science databases to identify pediatric studies comparing the pattern of fecal and respiratory shedding of SARS-CoV-2 RNA. Summary estimates were calculated using random-effects models. RESULTS: Four studies reporting data from 36 children were included. A higher proportion of children had viral shedding in stools after 14 days of symptoms onset compared to respiratory samples (RR= 3.2, 95%CI 1.2 to 8.9, I2 = 51%). Viral RNA shedding was longer in fecal samples with a mean difference of approximately 9 days (Mean Difference = 8.6, 95%CI 1.7 to 15.4, I2 = 77%) compared with respiratory samples. CONCLUSION: SARS-CoV-2 shedding seems to be present in feces for a longer time than in the respiratory tract of children. Although fecal SARS-CoV-2 presence in feces do not confirm its transmissibility, the high and fast spread of the COVID-19 disease worldwide indicate other transmission routes are also plausible.


title: Effects of aging on T cell function

text: Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current views on how aging influences the factors that impact T cell function and how this can affect the immune response to infections, vaccinations, and tumors.


title: Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

text: Human enterovirus 71 (EV71) infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE) on rhabdomyosarcoma (RD) cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.


title: Exploring disaster resilience within the hotel sector: A systematic review of literature

text: Abstract Within the tourism industry, the hotel sector's vulnerabilities are multi-faceted. This literature discussion scrutinizes how disaster and resilience is framed for the tourism sector, and, more specifically, how the concepts can be applied to the hotel sector. A synthesis of the literature points to the importance of prioritizing disaster resilience building for the hotel sector. The body of literature regarding disasters, tourism, and more specifically hotels, has increased over the last 20 years, still improvements in the hotel sector's disaster preparedness and do not appear to be on the same trajectory. Illustrating the predicament of the contemporary hotel industry serves to open a discussion about the value of building resiliency to disaster for hotels. As the numbers of people affected by disasters grows, the importance of providing actionable information to limit the severity of these events on communities also escalates in pace.


title: Modelling Emerging Viral Epidemics for Public Health Protection

text: Mathematical models when applied to infectious disease data can provide extremely useful insights into the possible future impacts of potential emerging epidemics and how they might be best controlled or mitigated. Modelling, which is like any other hypothesis-driven approach, aims to develop a better understanding of biological phenomena. However, diseases processes generally, and particularly those related to transmission, will in many cases be imperfectly understood or too complex to systematically describe, so models will necessarily be simplifications of the overall system. It is essential, therefore, that models are designed carefully and used appropriately. Key to this is identifying what specific questions a model might be expected to answer and what data is available to inform the model. A particular type of model might be fine for one particular situation but highly inappropriate for another. It is also important to appreciate and communicate what simplifications and assumptions have had to be made and how this might affect the robustness of the modelling results. It is also particularly important to understand that models frequently make what can be hidden assumptions about underlying processes because of the way they have been constructed and these assumptions also need to be carefully considered and made explicit, particularly for non-expert audiences. This chapter, therefore, provides a brief introduction to some of these aspects of epidemic modelling for those that might be less familiar with them.


title: Immunizations in the United States: A Rite of Passage

text: Today, vaccination is a cornerstone of pediatric preventive health care and a rite of passage for nearly all of the approximately 11,000 infants born daily in the United States. This article reviews the US immunization program with an emphasis on its role in ensuring that vaccines are effective, safe, and available and highlights several new vaccines and recommendations that will affect the health of children and adolescents and the practice of pediatric medicine in future decades.


title: Disease reservoirs: from conceptual frameworks to applicable criteria

text: Central to the One Health approach and any disease eradication program is the question of whether a pathogen has a non-human reservoir. Despite well-established conceptual frameworks that define a reservoir of infection, empirical characterization of reservoirs often remains controversial, challenging and sometimes misleading. What is essentially missing are applicable requirements that standardize the use of the term ‘reservoir of infection’ across multiple disciplines. We propose an empirical framework, considering maintenance and feasible transmission of a pathogen, to standardize the acceptance of a disease reservoir across multiple disciplines. We demonstrate the intended use of these requirements by applying them to different diseases that are known to infect both humans and animals.


title: COVID-19: clinical challenges in Dutch Geriatric Psychiatry

text: The COVID-19 pandemic has changed everyday life tremendously in a short period of time. After a brief timeline of the Dutch situation and our management strategy to adapt geriatric mental health care, we present a case-series to illustrate the specific challenges for geriatric psychiatrists.


title: Methods of Measuring Compliance with Transmission-Based Isolation Precautions: Comparison of Paper-Based and Electronic Data Collection

text: BACKGROUND: Decreasing transmission of resistant organisms in hospitals is a key goal of infection prevention plans. Studies have shown that health care worker (HCW) compliance with isolation precautions is inadequate. Direct observation of HCW behavior for measuring adherence is considered the “gold standard” but is labor intensive, requiring the collection and analysis of a large volume of observations. METHODS: Two methods of data collection were evaluated to asses HCW compliance: a manual method using a paper form (PF) with subsequent data entry into a database, and an electronic method using a web-based form (WBF) with real-time data recording. Observations were conducted at four hospitals (2,065 beds) to assess availability of gloves, gowns and masks, isolation sign postings, and HCW isolation practices. RESULTS: A total of 13,878 isolation rooms were observed in 2009. The median number of rooms observed/day for PF and WBF were 61 and 60 and the mean observation times/room were 149sec and 60sec, respectively. The WBF provided a time savings of 89 sec/room. CONCLUSIONS: Simple electronic forms can significantly decrease resources needed to monitor HCW adherence to hospital policies. The WBF decreased observation time by 60%, allowing for an increase in frequency and expansion of surveillance activities.


title: Disability through COVID‐19 pandemic: Neurorehabilitation cannot wait

text: Coronavirus disease 2019 (CoViD‐19) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time‐dependent diseases,(1) including CoViD‐19 complications.(2,3) Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection,(4) has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey,(5) possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger.


title: Abnormal liver function tests predict transfer to intensive care unit and death in COVID‐19

text: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID‐19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non‐critically ill patients with COVID‐19. METHODS: In this multicenter, retrospective study, we collected data about 565 inpatients with COVID‐19. Data on LFTs were collected at admission and every 7±2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20vs8%; p<0.001), acute kidney injury (22vs13%, p=0.009), need for mechanical ventilation (14vs6%; p=0.005), and mortality (21vs11%; p=0.004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR=3.53; p<0.001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID‐19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.


title: U.S. county level analysis to determine If social distancing slowed the spread of COVID-19

text: OBJECTIVE. To analyze the effectiveness of social distancing in the United States (U.S.). METHODS. A novel cell-phone ping data was used to quantify the measures of social distancing by all U.S. counties. RESULTS. Using a difference-in-difference approach results show that social distancing has been effective in slowing the spread of COVID-19. CONCLUSIONS. As policymakers face the very difficult question of the necessity and effectiveness of social distancing across the U.S., counties where the policies have been imposed have effectively increased social distancing and have seen slowing the spread of COVID-19. These results might help policymakers to make the public understand the risks and benefits of the lockdown.


title: Aminopeptidase activity in human nasal mucosa

text: Abstract Background: Aminopeptidases activate bradykinin and degrade many inflammatory peptides. Objective: The objective of this study was to identify the types of aminopeptidase activities in human nasal mucosa. Methods: Human nasal mucosa was homogenized (n = 12), and cytoplasmic (S2) and membrane-rich (P2) fractions were obtained. Several aminopeptidase (Ap) activities were defined by (1) substrate specificity with leucine-enkephalin (leu-Ap) and alanine-nitroanilide (ala-Ap), (2) inhibitor studies with puromycin and bestatin, (3) enzyme activity histochemistry (zymography), (4) immunohistochemistry, and (5) gel electrophoresis. Human volunteers had methacholine, histamine, and allergen nasal provocations to determine the mechanisms controlling nasal aminopeptidase secretion in vivo. Results: P2 was the largest reservoir of puromycin-resistant aminopeptidase activity (630 pmol leu-enk/min/mg protein). S2 contained 32 pmol leu-enk/min/mg activity, with 80% representing puromycin-resistant activity and 20% puromycin-sensitive aminopeptidase (PS-Ap). Ala-Ap was detected in both P2 and S2 fractions and was localized by zymography to epithelial and gland cells. Anti–rat brain–soluble PS-Ap IgG detected immunoreactive material in epithelium, glands, and endothelium. In nasal provocation studies, leu-AP correlated with glandular exocytosis but not vascular leak. Conclusions: The predominant aminopeptidase in human nasal epithelial and submucosal gland cells was membrane-bound puromycin-resistant aminopeptidase. A novel soluble puromycin-resistant aminopeptidase and lower amounts of soluble PS-Ap were also detected. (J Allergy Clin Immunol 1998;102:741-50.)


Coronavirus (COVID-19), First Indication of Efficacy of Gene-Eden-VIR/Novirin in SARS-CoV-2 Infections


docid: fffjcnak

title: Respiratory infections in the Asia‐Pacific region: Problems and cautious optimism


title: Phylogenetic and epidemic modeling of rapidly evolving infectious diseases

text: Abstract Epidemic modeling of infectious diseases has a long history in both theoretical and empirical research. However the recent explosion of genetic data has revealed the rapid rate of evolution that many populations of infectious agents undergo and has underscored the need to consider both evolutionary and ecological processes on the same time scale. Mathematical epidemiology has applied dynamical models to study infectious epidemics, but these models have tended not to exploit – or take into account – evolutionary changes and their effect on the ecological processes and population dynamics of the infectious agent. On the other hand, statistical phylogenetics has increasingly been applied to the study of infectious agents. This approach is based on phylogenetics, molecular clocks, genealogy-based population genetics and phylogeography. Bayesian Markov chain Monte Carlo and related computational tools have been the primary source of advances in these statistical phylogenetic approaches. Recently the first tentative steps have been taken to reconcile these two theoretical approaches. We survey the Bayesian phylogenetic approach to epidemic modeling of infection diseases and describe the contrasts it provides to mathematical epidemiology as well as emphasize the significance of the future unification of these two fields.


title: How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion

text: • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable.


title: The plasticity of inflammatory monocyte responses to the inflamed central nervous system

text: Abstract Over the last three decades it has become increasingly clear that monocytes, originally thought to have fixed, stereotypic responses to foreign stimuli, mediate exquisitely balanced protective and pathogenic roles in disease and immunity. This balance is crucial in core functional organs, such as the central nervous system (CNS), where minor changes in neuronal microenvironments and the production of immune factors can result in significant disease with fatal consequences or permanent neurological sequelae. Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. While antigen-specific lymphocyte populations are central to the adaptive immune response in both cases, in viral encephalitis a prominent macrophage infiltration may mediate immunopathological damage, seizure induction, and death. However, the autoimmune response to non-replicating, non-infectious, but abundant, self antigen has a different disease progression, associated with differentiation of significant numbers of infiltrating monocytes into dendritic cells in the CNS. Whilst a predominant presence of macrophages or dendritic cells in the inflamed CNS in viral encephalitis or multiple sclerosis is well described, the way in which the inflamed CNS mobilizes monocytes in the bone marrow to migrate to the CNS and the key drivers that lead to these specific differentiation pathways in vivo are not well understood. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes.


title: Structural analysis of the conformational domains involved in neutralization of bovine coronavirus using deletion mutants of the spike glycoprotein S1 subunit expressed by recombinant baculoviruses

text: Abstract Two conformation-dependent neutralizing epitopes, A and B, have been mapped to the S1 subunit of the S spike glycoprotein of bovine coronavirus (BCV). In order to characterize the structure of these antigenic sites, we constructed a series of cDNA clones encoding deleted or truncated S1 derivatives and expressed the modified genes in insect cells using recombinant baculoviruses. Monoclonal antibodies directed against epitopes A and B recognized only the mutant S1 polypeptides containing amino acids 324–720, as demonstrated by immunoprecipitation and Western blot analysis in the absence of β-mercaptoethanol. In addition, two domains within this region were identified and only mutants containing both domains were immunoreactive, indicating that both were critical in the formation of the antigenic determinants. One domain was localized between residues 324 and 403 and the other at residues 517–720. Deletion of either domain inhibited extracellular secretion of the mutant proteins whereas mutants containing both or none of the domains were secreted efficiently. This observation suggests a vital function of the native conformation of the S1 protein in both antigenic structure and intracellular transport. Antigenic determinants A and B were not distinguished, but these determinants appeared to require both domains for epitope formation. Our results suggest that the antigenic determinants formed by two domains are likely associated with the probable polymorphic region of the BCV S1 subunit.


title: Engineering passive immunity in transgenic mice secreting virus-neutralizing antibodies in milk

text: Protection against enteric infections can be provided by the oral administration of pathogen-neutralizing antibodies. To provide passive immunity, 18 lines of transgenic mice secreting a recombinant monoclonal antibody (Mab) neutralizing transmissible gastroenteritis coronavirus (TGEV) into the milk were generated. The genes encoding a chimeric Mab with the variable modules of the murine TGEV-specific Mab 6A.C3 and the constant modules of a human IgG(1), isotype Mab were expressed under the control of regulatory sequences derived from the whey acidic protein, which is an abundant milk protein. The Mab 6A.C3 binds to a highly conserved epitope present in coronaviruses of several species, which does not allow the selection of neutralization escape mutants. Antibody expression titers of 10(6) were obtained in the milk of transgenic mice that reduced TGEV infectivity 10(6)-fold. The antibody was synthesized at high levels throughout lactation. Integration of matrix attachment region sequences with the antibody genes led to a 20- to 10,000-fold increase in the antibody titer in 50% of the transgenic animals. Antibody expression levels were transgene copy number independent and related to the site of integration. The generation of transgenic animals producing virus neutralizing antibodies in milk could provide an approach to protection against neonatal infections of the enteric tract.


title: Forecasting the timeframe of coronavirus and human cells interaction with reverse engineering

text: Abstract In December 2019, an atypical pneumonia invaded the city of Wuhan, China, and the causative agent of this disease turned out to be a new coronavirus. In January 2020, the World Health Organization named the new coronavirus 2019-nCoV and subsequently it is referred to as SARS-CoV2 and the related disease as CoViD-19 [9]. Very quickly, the epidemic led to a pandemic and it is now a worldwide emergency requiring the creation of new antiviral therapies and a related vaccine. The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the “entry receptor” for the infection process involving membrane fusion [10]. A reverse engineering process uses the formalism of the Hill function to represent the functions related to the dynamics of the biochemical interactions of the viral infection process. Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the “time delay” given by the interaction between cell and virus, the expected duration of the incubation period is predicted. The conclusion is that the density of the virus varies from the “exposure time” to the “interaction time” (virus-cells). This model can be used both to evaluate the infectious condition and to analyze the incubation period. Background The ongoing threat of the new coronavirus SARS-CoV2 pandemic is alarming and strategies for combating infection are highly desired. This RNA virus belongs to the β-coronavirus genus and is similar in some features to SARS-CoV. Currently, no vaccine or approved medical treatment is available. The complex dynamics of the rapid spread of this virus can be demonstrated with the aid of a computational framework. Methods A mathematical model based on the principles of cell-virus interaction is developed in this manuscript. The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function. The mathematical model with delay is solved with the aid of numerical solvers and the parametric values are obtained with the help of MCMC algorithm. Results A delay differential equation model is developed to demonstrate the dynamics of target cells, infected cells and the SARS-CoV2. The important parameters and coefficients are demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be useful tools for future experimental studies and control strategies. Conclusions From the analysis, I is concluded that control strategy via delay is a promising technique and the role of Hill function formalism in control strategies can be better interpreted in an inexpensive manner with the aid of a theoretical framework.


Narrative medicine: thinking with stories during The Plague


COVID-19 spread: the Italian case


title: Super-spreaders in infectious diseases

text: Summary Early studies that explored host–pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.


title: Colon capsule endoscopy: an innovative method for detecting colorectal pathology during the COVID‐19 pandemic?

text: AIM: The coronavirus pandemic has led to significant challenges for healthcare delivery across the globe. Non‐emergency endoscopic activity in the UK has been postponed, raising concerns of increased delays in the diagnosis of colorectal cancer and a surge in demand once services resume. Measures to mitigate this risk must be considered. METHOD: This paper reviews various investigative modalities for colorectal disease which could be deployed during cessation of colonoscopy services. We focus on colon capsule endoscopy (CCE) due to its relevance during the COVID‐19 pandemic and its ability to triage patients effectively to further endoscopic investigations. RESULTS: CT of the abdomen and pelvis has been suggested as a triage tool while access to colonoscopy is limited. However, CT may lead to the spread of COVID‐19 as patients attend the hospital, and it exposes them to the risks of radiation. Faecal immunochemistry tests have been demonstrated as a good predictor of colonic pathology and could be safely used to risk stratify patients when prioritizing colonoscopy. CCE is a safe and innovative technology for investigating the colon. Procedures can be carried out in the community and can be conducted safely during the coronavirus pandemic. It has been shown to be an accurate detector of colonic neoplasia and can reduce demand for colonoscopy. CONCLUSION: As colonoscopy services resume, they will probably experience high demand leading to further delays for patients. CCE could be used to reduce the number of patients requiring colonoscopy and triage those requiring further endoscopic investigations appropriately.


title: Assessment of temporally-related acute respiratory illness following influenza vaccination

text: Abstract Background A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods. Methods We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons. Results Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]). Conclusion Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.


title: Optical sensor for berberine utilizing its intrinsic fluorescence enhanced by the formation of inclusion complex with butylated-β-cyclodextrin

text: Abstract An optical sensor for berberine, the basic ingredient of the widely used traditional Chinese medicine Coptis Chinensis, based on its intrinsic fluorescence enhanced by butylated-β-cyclodextrin (HDB-β-CD) immobilized in plasticized poly(vinyl chloride) (PVC) membrane has been developed. The drastic enhancement of fluorescence intensity of berberine was attributed to the formation of an inclusion complex between HDB-β-CD and berberine, which has been utilized as the basis of the fabrication of a berberine-sensitive fluorescence sensor. The proposed sensor was quite distinct from those fluorescent sensors for berberine reported so far which relied upon quenching the fluorescence of the sensing reagent immobilized on membrane by berberine. The response mechanism of optode membrane was discussed in detail from the view of molecular dynamics and the optimum steric configuration of the inclusion complex was presented by molecular dynamics simulation. The analytical performance characteristics of the proposed berberine-sensitive sensor were investigated. The sensor can be applied to the quantification of berberine with a linear range covering from 4.0×10−7 to 2.0×10−5 moll−1 with a detection limit of 8.0×10−8 moll−1. The sensor exhibits excellent reproducibility, reversibility and selectivity. The recommended method was successfully used for the determination of berberine in pharmaceutical preparations.


title: A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

text: Group A rotaviruses (RVAs) are a major cause of serious intestinal disease in piglets. In this study, a novel pig strain was identified in a stool sample from China. The strain was designated RVA/Pig/China/LNCY/2016/G3P[13] and had a G3‐P[13]‐I5‐R1‐C1‐M1‐A8‐N1‐T1‐E1‐H1 genome. The viral protein 7 (VP7) and non‐structural protein 4 (NSP4) genes of RVA/Pig/China/LNCY/2016/G3P[13] were closely related to cogent genes of human RVAs, suggesting that a reassortment between pig and human strains had occurred. Recombination analysis showed that RVA/Pig/China/LNCY/2016/G3P[13] is a natural recombinant strain between the P[23] and P[7] RVA strains, and crossover points for recombination were found at nucleotides (nt) 456 and 804 of the VP4 gene. Elucidating the biological characteristics of porcine rotavirus (PoRV) will be helpful for further analyses of the epidemic characteristics of this virus. The results of this study provide valuable information for RVA recombination and evolution and will facilitate future investigations into the molecular pathogenesis of RVAs.


title: Ebola Virus Disease Clinical Challenges, Recognition, and Management

text: The 2014 to 2016 Ebola outbreak response resulted in many lessons learned about biocontainment patient care, leading to enhanced domestic capabilities for highly infectious and hazardous communicable diseases. However, additional opportunities for improvement remain. The article identifies and describes key considerations and challenges for laboratory analysis, clinical management, transportation, and personnel management during the care of patients infected with Ebola or other special pathogens. Dedication to maintaining preparedness enables biocontainment patient care teams to perform at the highest levels of safety and confidence.


title: A feasibility study of conducting surveillance for swine pathogens in slurry from North Carolina swine farms

text: Despite close contact between humans and animals on large scale farms, little to no infectious disease research is conducted at this interface. Our goal in this preliminary study was to explore if we could detect swine pathogens using a non-invasive, indirect approach through the study of swine slurry. From April to November 2018, 105 swine slurry samples were collected by farm personnel from waste pits at two sites on a swine farm in North Carolina. These samples were tested for DNA and RNA viruses using a real-time PCR and RT-PCR. Statistical analyses were performed to measure association between virus positive outcomes and potential predictors such as date of sample collection, weight of pigs, number of pigs in barn, temperature, and weather conditions. Overall, 86% of the samples had evidence of at least one of the targeted viruses. Ultimately, this study demonstrated the utility of conducting noninvasive surveillance for swine pathogens through the study of swine slurry. Such swine slurry surveillance may supplant the need to handle, restrain, and collect specimens directly from pigs thus providing an approach to emerging pathogen detection that appeals to the swine industry.


title: Epidemiological characteristics of human-infective RNA viruses

text: RNA viruses are a major threat to human health. Here, based on extensive literature searches carried out over a period of 18 years, we provide a catalogue of all 214 known human-infective RNA virus species. We link these viruses to metadata for a number of traits that influence their epidemiology, including the date of the first report of human infection, transmissibility in human populations, transmission route(s) and host range. This database can be used in comparative studies of human-infective RNA viruses to identify the characteristics of viruses most likely to pose the greatest public health threat, both now and in the future.


title: Genetic Characteristics of Coronaviruses from Korean Bats in 2016

text: Bats have increasingly been recognized as the natural reservoir of severe acute respiratory syndrome (SARS), coronavirus, and other coronaviruses found in mammals. However, little research has been conducted on bat coronaviruses in South Korea. In this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in South Korea. RT-PCR and sequencing were performed for specific coronavirus genes to identify the bat coronaviruses in different bat samples. Coronaviruses were detected in 2.7% (18/672) of the samples: 13 oral swabs from one species of the family Rhinolophidae, and four fecal samples and one carcass (intestine) from three species of the family Vespertiliodae. To determine the genetic relationships of the 18 sequences obtained in this study and previously known coronaviruses, the nucleotide sequences of a 392-nt region of the RNA-dependent RNA polymerase (RdRp) gene were analyzed phylogenetically. Thirteen sequences belonging to SARS-like betacoronaviruses showed the highest nucleotide identity (97.1–99.7%) with Bat-CoV-JTMC15 reported in China. The other five sequences were most similar to MERS-like betacoronaviruses. Four nucleotide sequences displayed the highest identity (94.1–95.1%) with Bat-CoV-HKU5 from Hong Kong. The one sequence from a carcass showed the highest nucleotide identity (99%) with Bat-CoV-SC2013 from China. These results suggest that careful surveillance of coronaviruses from bats should be continued, because animal and human infections may result from the genetic variants present in bat coronavirus reservoirs.


The Income-Based Mortality Gradient Among US Health Care Workers: Cohort Study


How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramakrishnan N. Critical Care Epidemiology and Research in the Face of a Pandemic: An Opportunity in a Crisis. Indian J Crit Care Med 2020;24(4):242–244.


Evaluation of the Slit Lamp Shield to reduce droplet exposure


title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster

text: Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.


title: Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9)

text: Abstract We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations.


A Google Trends study on the interest in self-medication during the 2019 novel Coronavirus (COVID-19) disease pandemic


title: A Heuristic Indication and Warning Staging Model for Detection and Assessment of Biological Events

text: OBJECTIVE: This paper presents a model designed to enable rapid detection and assessment of biological threats that may require swift intervention by the international public health community. DESIGN: We utilized Strauss’ grounded theory to develop an expanded model of social disruption due to biological events based on retrospective and prospective case studies. We then applied this model to the temporal domain and propose a heuristic staging model, the Wilson–Collmann Scale for assessing biological event evolution. MEASUREMENTS: We retrospectively and manually examined hard copy archival local media reports in the native vernacular for three biological events associated with substantial social disruption. The model was then tested prospectively through media harvesting based on keywords corresponding to the model parameters. RESULTS: Our heuristic staging model provides valuable information about the features of a biological event that can be used to determine the level of concern warranted, such as whether the pathogen in question is responding to established public health disease control measures, including the use of antimicrobials or vaccines; whether the public health and medical infrastructure of the country involved is adequate to mount the necessary response; whether the country’s officials are providing an appropriate level of information to international public health authorities; and whether the event poses a international threat. The approach is applicable for monitoring open-source (public-domain) media for indications and warnings of such events, and specifically for markers of the social disruption that commonly occur as these events unfold. These indications and warnings can then be used as the basis for staging the biological threat in the same manner that the United States National Weather Service currently uses storm warning models (such as the Saffir-Simpson Hurricane Scale) to detect and assess threatening weather conditions. CONCLUSION: Used as a complement to current epidemiological surveillance methods, our approach could aid global public health officials and national political leaders in responding to biological threats of international public health significance.


title: Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates

text: Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the recently recognized Arteriviridae family within the genus Arterivirus, order Nidovirales, which also includes equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV). Mature viral particles are composed of an envelope 50–72 nm in diameter, with an isometric core about 20–30 nm enclosing a linear positive-stranded RNA genome of approximately 15 kb. The virions are assembled by the budding of preformed nucleocapsids into the lumen of the smooth endoplasmic reticulum and/or Golgi apparatus. The mature virions are then released by exocytosis. The viral genome contains eight open reading frames (ORFs) which are transcribed in cells as a nested set of subgenomic mRNAs. The ORF1a and ORF1b situated at the 5′end of the genome represent nearly 75% of the viral genome and code for proteins with apparent replicase and polymerase activities. The major structural proteins consist of a 25 kDa envelope glycoprotein (GP(5)), an 18–19 kDa unglycosylated membrane protein (M), and a 15 kDa nucleocapsid (N) protein, encoded by ORFs 5, 6 and 7, respectively. The N protein is the more abundant protein of the virion and is highly antigenic, which therefore makes it a suitable candidate for the detection of virus-specific antibodies and diagnosis of the disease. Four to five domains of antigenic importance have been identified for the N protein, a common conformational antigenic site for European and North American strains being localized in the central region of the protein. In cells and virions, both M and GP(5) occur in heterodimeric complexes linked by disulfide bonds. The expression products of ORFs 2 and 4 are also incorporated into virus particles as additional minor membrane-associated glycoproteins designated as GP(2) and GP(4), with M(r) of 29 and 31 kDa, respectively. The structural nature of the ORF3 product, a highly glycosylated protein with an apparent M(r) of 42 kDa, is still being debated, in view of the apparently conflicting data on its presence in virus particles. Nonetheless, the GP(3) of North American and European strains has been shown to be antigenic, providing protection for piglets against PRRSV infection in the absence of a noticeable neutralizing humoral response. Pigs exposed to the native form of GP(5) by means of DNA immunization develop specific neutralizing and protecting antibodies. The GP(5) is involved in antigenic variability, apoptosis, and possibly antibody-dependent enhancement phenomena. The GP(4) also possesses antigenic determinants that trigger the immune system to produce neutralizing antibodies. Each of the PRRSV structural proteins carries common and type-specific antigenic determinants that permit the ability to differentiate between European and North American strains. The potential use of the PRRSV structural proteins in subunit recombinant-type vaccines is also discussed.


title: Research agenda for mass gatherings: a call to action

text: Summary Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.


“Thinking outside the box in COVID‐19 era”‐Application of Modified Aerosol Box in Dermatology


title: Outcomes of Hematopoietic Stem Cell Transplant Recipients with Rhinovirus Infection: A Matched, Case-Control Study

text: The impact of rhinovirus in hematopoietic stem cell transplant (HSCT) recipients is not well defined. A retrospective, matched, case-control study of HSCT recipients with rhinovirus was conducted between 2009 and 2011. Controls were matched for timing relative to transplant, malignancy, and stem cell source. There were 47 cases and 94 controls. Cases and controls did not differ with respect to age, gender, ethnicity, donor source, malignancy, conditioning regimen, immunosuppression, antimicrobial prophylaxis, or significant comorbidities. There were no differences in need for ICU care, 100 day mortality, hospice discharge, relapse of disease, GVHD or development of disease or infection due to CMV or EBV. Other infectious complications after rhinovirus diagnosis were also equal. However, there was an increased number of recurrent hospitalizations from any cause among cases (46.8% vs. 24.5%, P=0.007). Recurrent hospitalizations due to any infection were also more common in cases (34% vs. 14.9%, P=0.015). For patients who were diagnosed with rhinovirus pre-transplant (n=13), there was no difference in outcomes compared to matched controls. HSCT recipients with rhinovirus have an increased risk of hospital readmission. However, there was no difference in outcomes compared to matched controls. Transplantation in patients with active rhinovirus infection appears to be safe.


title: Influence of wind and relative humidity on the social distancing effectiveness to prevent COVID-19 airborne transmission: A numerical study

text: It has been confirmed that the coronavirus disease 2019 (COVID-19) can transmit through droplets created when an infected human coughs or sneezes. Accordingly, 1.83-m (6-feet) social distancing is advised to reduce the spread of the disease among humans. This is based on the assumption that no air circulation exists around people. However, it is not well investigated whether the ambient wind and relative humidity (RH) will cause SARS-CoV-2 laden droplets to transport farther in the air, making the current social distancing policy insufficient. To provide evidence and insight into the “social distancing” guidelines, a validated computational fluid-particle dynamics (CFPD) model was employed to simulate the transient transport, condensation/evaporation, and deposition of SARS-CoV-2 laden droplets emitted by coughs, with different environmental wind velocities and RHs. Initial droplet diameters range from 2 to 2000 μm, and the wind velocities range from 0 to 16 km/h, representing different wind forces from calm air to moderate breeze. The comparison between a steady-state wind and a gust with a constant frequency has also been performed. Ambient RHs are 40% and 99.5%. The distances between the two virtual humans are 1.83 m and 3.05 m (6 feet and 10 feet). The facial covering effect on reducing the airborne transmission of the cough droplets has also been evaluated. Numerical results indicate that the ambient wind will enhance the complexity of the secondary flows with recirculation between the two virtual humans. Microdroplets follow the airflow streamlines well and deposit on both human bodies and head regions, even with the 3.05-m (10-feet) separation distance. The rest of the microdroplets can transport in the air farther than 3.05 m (10 feet) due to wind convection, causing a potential health risk to nearby people. High RH will increase the droplet sizes due to the hygroscopic growth effect, which increases the deposition fractions on both humans and the ground. With the complex environmental wind and RH conditions, the 6-feet social distancing policy may not be sufficient to protect the inter-person aerosol transmission, since the suspending micro-droplets were influenced by convection effects and can be transported from the human coughs/sneezes to the other human in less than 5 s. Thus, due to the complex real-world environmental ventilation conditions, a social distance longer than 6 feet needs to be considered. Wearing masks should also be recommended for both infected and healthy humans to reduce the airborne cough droplet numbers.


title: Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks

text: Abstract The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.


title: Recombinant M protein-based ELISA test for detection of antibodies to canine coronavirus

text: Abstract The membrane (M) protein of canine coronavirus (CCoV) was cloned and expressed in E. coli. The purified recombinant protein was then evaluated for its antigenicity and reliability in an enzyme-linked immunosorbent assay (ELISA) for detection of CCoV antibodies in dog sera. Fifty serum samples, screened previously by whole virus ELISA and Western blotting, were tested. When the performance of the new test was compared with those of whole virus ELISA and Western blotting, an excellent correlation was found with the latter two assays. The ELISA based on recombinant M protein represents an alternative and valid test for detection of antibodies to CCoV in dog sera.


title: COVID-19 and the 5G Conspiracy Theory: Social Network Analysis of Twitter Data

text: BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph’s vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.


title: Diseases associated with spontaneous feline leukemia virus (FeLV) infection in cats

text: Abstract More than 2000 cats sent for necropsy in order to provide a diagnosis were investigated immunohistologically using paraffin sections for the presence of a persistent infection with feline leukemia virus (FeLV). The spectrum of neoplastic and non-neoplastic diseases associated significantly with FeLV infection was determined statistically. Three-quarters of the cats with persistent FeLV infections died of non-neoplastic diseases and about 23% died of tumors, nearly exclusively those of the leukemia/lymphoma disease complex. A strong association with liver degeneration, icterus and a FeLV-associated enteritis was found in addition to the known association with non-neoplastic diseases and conditions such as anemia, bacterial secondary infections and respiratory tract inflammations due to the immunosuppressive effect of FeLV, hemorrhages and feline infectious peritonitis. Surprisingly, diseases and conditions like feline infectious panleukopenia, enteritis (of other types than FeLV-associated enteritis and feline infectious panleukopenia), glomerulonephritis, uremia and hemorrhagic cystitis were not associated with persistent FeLV infection. Another unexpected finding was that most pathogenic infectious agents demonstrated in the cats were not FeLV-associated either. Thus, immunosuppression due to FeLV infection seems to make the animals susceptible to certain pathogenic infectious agents, but not to the majority.


docid: wiwpozji

title: Human Rhinovirus Proteinase 2A Induces Th1 and Th2 Immunity in COPD

text: BACKGROUND: Tobacco related lung diseases including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory viral infections and may result in respiratory failure in those with advanced lung disease. OBJECTIVE: We sought to determine the mechanism underlying COPD exacerbation, and host response to pathogen-derived factors. METHODS: Over a 24 months period, we assessed the viral causes for upper and lower respiratory infections in COPD (n=155) and control (n=103) subjects. We collected nasal and bronchoalveolar lavage (BAL) fluid and peripheral blood under baseline and exacerbated condition. We determined the effect of human rhinovirus (HRV) proteinases on T cell activation in humans, and in mice. RESULTS: HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. BAL fluid, and CD4 T cells from COPD patients exhibited a type 1 T helper (Th1), and Th2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro, and induced strong Th1, and Th2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells. CONCLUSION: Our findings suggest that patients with severe COPD show Th1 and Th2 bias responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a Th1 and Th2-biasing adjuvant factor during upper and lower respiratory infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases may contribute to worsening of dyspnea and respiratory failure in COPD.


SARS, lay epidemiology, and fear


title: QSAR Models for Predicting Cathepsin B Inhibition by Small Molecules: Continuous and Binary QSAR Models to Classify Cathepsin B Inhibition Activities of Small Molecules

text: Cathepsin B is a potential target for the development of drugs to treat several important human diseases. A number of inhibitors targeting this protein have been developed in the past several years. Recently, a group of small molecules were identified to have inhibitory activity against cathepsin B through high throughput screening (HTS) tests. In this study, traditional continuous and binary QSAR models were built to classify the biological activities of previously identified compounds and to distinguish active compounds from inactive compounds for drug development based on the calculated molecular and physicochemical properties. Strong correlations were obtained for the continuous QSAR models with regression correlation coefficients (r(2)) and cross-validated correlation coefficients (q(2)) of 0.77 and 0.61 for all compounds, and 0.82 and 0.68 for the compound set excluding 3 outliers, respectively. The models were further validated through the leave-one-out (LOO) method and the training-test set method. The binary models demonstrated a strong level of predictability in distinguishing the active compounds from inactive compounds with accuracies of 0.89 and 0.94 for active and inactive compounds, respectively, in non-cross-validated models. Similar results were obtained for the cross-validated models. Collectively, these results demonstrate the models’ ability to discriminate between active and inactive compounds, suggesting that the models may be used to pre-screen compounds to facilitate compound optimization and to design novel inhibitors for drug development.


title: Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles

text: The folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective production of nanoparticle (NP) vaccines in a timely and reproducible manner. Despite significant advances in in silico design and structure-based assembly, most engineered NPs are refractory to soluble expression and fail to assemble as designed, presenting major challenges in the manufacturing process. The failure is due to a lack of understanding of the kinetic pathways and enabling technical platforms to ensure successful folding of the monomer antigens into regular assemblages. Capitalizing on a novel function of RNA as a molecular chaperone (chaperna: chaperone + RNA), we provide a robust protein-folding vehicle that may be implemented to NP assembly in bacterial hosts. The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a soluble form. Site-specific proteolytic removal of the RID prompted the assemblage of monomers into NPs, which was confirmed by electron microscopy and dynamic light scattering. The mutations that affected the RNA binding to RBD significantly increased the soluble aggregation into amorphous structures, reducing the overall yield of NPs of a defined size. This underscored the RNA-antigen interactions during NP assembly. The sera after mouse immunization effectively interfered with the binding of MERS-CoV RBD to the cellular receptor hDPP4. The results suggest that RNA-binding controls the overall kinetic network of the antigen folding pathway in favor of enhanced assemblage of NPs into highly regular and immunologically relevant conformations. The concentration of the ion Fe(2+), salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic “pace-keeping” role of chaperna in the super molecular assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serological detection of viral infections.


title: Immunohistochemistry analysis of pulmonary infiltrates in necropsy samples of children with non-pandemic lethal respiratory infections (RSV; ADV; PIV1; PIV2; PIV3; FLU A; FLU B)

text: Abstract Background Acute viral respiratory infections represent a globally important cause of morbidity and mortality in childhood. An individual's cellular response appears to play a critical role in recovery from infections, given that individuals with impaired cellular immunity, congenital or acquired, have more severe diseases and secrete the virus for longer periods. Objectives The aim of this study was to immunohistochemically evaluate the expression of the cell surface antigens CD4, CD8, CD25, CD14 and CD74, in pneumonic infiltrates in the alveolar septa using paraffin-embedded lung samples from autopsies of immunocompetent children who died of lethal, non-pandemic, severe acute respiratory infections. Study design From 794 cases of pediatric autopsies of patients with severe respiratory disease (between 1960 and 2004), 193 cases were selected for this study. To identify subpopulations of inflammatory cells in the alveolar septa, cell surface antigen expression was assessed by immunohistochemistry using the following primary antibodies: anti-CD4, anti-CD8, anti-CD14, anti-CD25 and anti-CD74. Results The TCD8+ lymphocyte count was higher in the virus-positive group (p =0.04) and was also much higher among cases that were positive for more than three viral types (p =0.016). There were fewer CD14+ cells in cases of AdV (adenovirus) infection (p =0.002), and there was a predominance of CD74+ cells in the histopathological pattern defined as interstitial pneumonitis (p =0.037). Conclusions The results of this study demonstrate that TCD8+ lymphocytes present in the alveolar septa participate to a greater extent in the response toward viral pneumonia, while CD14+ cell numbers are often reduced in cases of AdV.


title: Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

text: Coronaviruses, including SARS-CoV-2 the etiological agent of COVID-19 disease, have caused multiple epidemic and pandemic outbreaks in the past 20 years(1–3). With no vaccines, and only recently developed antiviral therapeutics, we are ill equipped to handle coronavirus outbreaks(4). A better understanding of the molecular mechanisms that regulate coronavirus replication and pathogenesis is needed to guide the development of new antiviral therapeutics and vaccines. RNA secondary structures play critical roles in multiple aspects of coronavirus replication, but the extent and conservation of RNA secondary structure across coronavirus genomes is unknown(5). Here, we define highly structured RNA regions throughout the MERS-CoV, SARS-CoV, and SARS-CoV-2 genomes. We find that highly stable RNA structures are pervasive throughout coronavirus genomes, and are conserved between the SARS-like CoV. Our data suggests that selective pressure helps preserve RNA secondary structure in coronavirus genomes, suggesting that these structures may play important roles in virus replication and pathogenesis. Thus, disruption of conserved RNA secondary structures could be a novel strategy for the generation of attenuated SARS-CoV-2 vaccines for use against the current COVID-19 pandemic.


docid: rujylmib

title: Comparison of reverse transcription loop-mediated isothermal amplification, conventional PCR and real-time PCR assays for Japanese encephalitis virus

text: We developed and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting Japanese encephalitis virus (JEV). The sensitivity of the JEV RT-LAMP assay was in concordance with that of real-time RT-PCR and 10-fold more sensitive than that of conventional RT-PCR, which the detection limit was 24 copies/μl. The JEV RT-LAMP was highly specific, which no cross-reactivity was found with dengue-2 virus, rabies virus, norovirus, astrovirus and human enterovirus 71. The JEV RT-LAMP assay was more simple and less time-consuming compared to the conventional RT-PCR and real-time RT-PCR, which the amplification could be completed in a single tube within 1 h under isothermal conditions at temperature of 63°C. The results suggest that the RT-LAMP assay can be applied as a practical molecular diagnostic tool for JEV infection and surveillance.


title: Cellular DNA quantification in respiratory samples for the normalization of viral load: a real need?

text: Abstract Background Respiratory tract infections have an enormous social economic impact, with high incidence of hospitalization and high costs. Adequate specimen collection is the first crucial step for the correct diagnosis of viral respiratory infections. Objectives The present retrospective study aimed: i) to verify the cell yield obtained from sampling the nasal respiratory tract using mid-turbinate flocked swabs; ii) to evaluate the normalization of viral load, based on cell number; and iii) to compare the kinetics of viral infection obtained with normalized vs non-normalized viral load. Study design The number of cells were quantified by real-time PCR in residual extract of nasal swabs tested for respiratory viruses detection and stored at −80 °C in a universal transport medium (UTM™). Results A total of 513 virus-positive and 226 virus-negative samples were analyzed. Overall, a median of 4.42 log10 β2-microgolubin DNA copy number/ml of UTM™ (range 1.17–7.26) was detected. A significantly higher number of cells was observed in virus-positive as compared to virus-negative samples (4.75 vs 3.76; p < 0.001). Viral loads expressed as log10 RNA copies/ml of UTM™ and log10 RNA copies/median number of cells were compared in virus-positive samples and a strict correlation (r = 0.89, p < 0.001) and agreement (R2 = 0.82) were observed. In addition, infection kinetics were compared using the two methods with a follow-up series of eight episodes of viral infection and the mean difference was -0.57 log10 (range −1.99 to 0.40). Conclusions The normalization of viral load using cellular load compliments the validation of real-time PCR results in the diagnosis of respiratory viruses but is not strictly needed.


title: Development of a triplex real-time RT-PCR assay for detection and differentiation of three US genotypes of porcine hemagglutinating encephalomyelitis virus

text: Abstract Porcine hemagglutinating encephalomyelitis virus (PHEV) is a single-stranded, positive-sense RNA virus. PHEV mainly causes two types of clinical manifestations representing vomiting and wasting and encephalomyelitis in piglets. However, our recent findings provide strong evidence that PHEV can also cause respiratory disease in older pigs. Genomic analysis of new PHEV strains identified in our former study further classifies PHEV into three genotypes. Detection and differentiation of these new mutants are critical in monitoring PHEV evolution in the field. In the present study, we report the development of a triplex real-time RT-PCR assay for detection and differentiation of three PHEV genotypes, 1, 2, and 3. Three sets of primers and probes were designed; one set of primers and probe targeting the conserved regions of the 3′ end nucleocapsid for detection of all three genotypes and another two sets of primers and probes targeting the regions of NS2 with different patterns of deletions for detection of both genotypes 1 and 3, or genotype 3 only. Genotype 1 was positive when two probe dyes showed signals, genotype 2 was positive when only one probe dye showed a signal, and genotype 3 was positive when all three probes showed signals. The detection limit of the developed triplex real-time RT-PCR was as low as 8 or 9 DNA copies for three sets of primers and probes. The specificity test showed no cross reaction with other porcine viruses. Positive field-samples were correctly typed by this new assay, which was further confirmed by DNA sequencing. The triplex real-time RT-PCR provides a rapid and sensitive method to detect and differentiate all three US genotypes of PHEV from clinical samples.


title: Coronavirus SARS‐CoV‐2: filtering fact from fiction in the infodemic: Q&A with virologist Professor Urs Greber

text: As the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) continues to spread across the world, and the associated lung disease COVID-19 remains difficult to treat, information from media and private communication flows at high speed, often through unfiltered channels. Much of this information is speculative, as it derives from preliminary and inconclusive studies, and creates confusion as well as anxiety. This phenomenon was recently labelled as "infodemic" by the World Health Organization.


title: Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

text: Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.


docid: uyuazdhk

title: Validation and Psychometric Evaluation of the Italian Version of the Fear of COVID-19 Scale

text: BACKGROUND: The advent of COVID-19 worldwide has led to consequences for people’s health, both physical and psychological, such as fear and anxiety. This is the case in Italy, one of the countries most affected by the pandemic. Given the heightened fear concerning COVID-19 in Italy., the present study analyzed the psychometric properties of the Italian version of the Fear of COVID-19 Scale (FCV-19S). METHODS: The sample comprised 250 Italian participants who were administered Italian versions of the FCV-19S, the Hospital Anxiety and Depression Scale (HADS), and the Severity Measure for Specific Phobia–Adult (SMSP-A). Several psychometric tests were performed to investigate the validity and reliability of the test including confirmatory factor analysis. RESULTS: Analysis of the data showed satisfactory psychometric characteristics and confirmed the scale’s unidimensional properties. The seven FCV-19S items had acceptable correlations with the test total (from .443 to .784). Furthermore, the loadings on the factor were significant and strong (from .684 to .897). The internal consistency was very good (α = .871). Construct validity for the FCV-19S was supported by significant and positive correlations with the HADS (r=.649) and SMSP-A (r=.703). CONCLUSIONS: The Italian version of the Fear of COVID-19 Scale is valid and reliable in assessing fear of COVID-19 among the general Italian population.


title: A Systematic Review of Cases of Acute Respiratory Distress Syndrome in the Coronavirus Disease 2019 Pandemic

text: The outbreak of coronavirus disease 2019 (COVID-19) was declared a global pandemic after it spread to 213 countries and has the highest total number of cases worldwide. About 80% of COVID-19 infections are mild or asymptomatic and never require hospitalization but about 5% of patients become critically ill and develop acute respiratory distress syndrome (ARDS). The widely used management for ARDS in COVID-19 has been in line with the standard approach, but the need to adjust the treatment protocols has been questioned based on the reports of higher mortality risk among those requiring mechanical ventilation. Treatment options for this widespread disease are limited and there are no definitive therapies or vaccines until now. Although some antimalarial and antiviral drugs may prove effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their safety and efficacy are still under clinical trials. We conducted a systematic review of case reports on ARDS in SARS-CoV-2 infection to summarize the clinical presentation, laboratory and chest imaging findings, management protocols, and outcome of ARDS in COVID-19-positive patients. We need more data and established studies for the effective management of the novel SARS-CoV-2 and to reduce mortality in high-risk patients.


docid: gopgjsir

title: A real-time reporting system of causes of death or reasons for euthanasia: A model for monitoring mortality in domesticated cats in Taiwan

text: Abstract A novel, real-time mortality recording system was designed to collect mortality data in companion animals from veterinary hospitals in Taiwan. This retrospective study aims to introduce the system, and to utilize the data collected for further investigation of the lifespan and mortality of the domesticated cat population stratified by demographic variables. Our data revealed that 1325 domesticated cats were acquired between 2012 and 2014. The median age of the study population was 8.0 years (IQR 3.0–13.0; range 0.0–22.7). Neutered and purebred cats lived longer. The most common causes of death were renal and urologic disorders, followed by neoplasia, infection, cardiovascular disorders, and trauma. Independent factors for common causes were surveyed. Advanced age and neutering was found to be associated with death due to renal and urologic disorders as well as with neoplasia. In contrast, younger age was found to be associated with death due to trauma and infection; being unneutered and living in the capital city were found to be associated with death due to trauma. Being male or purebred was found to be associated with death due to cardiovascular disorders.


title: Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA

text: BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.


title: Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine

text: Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes and those induced by environmental and endogenous factors. The former enable accurate activation of developmental programs; the latter drive epigenetic responses to factors that directly or indirectly affect epigenetic biochemistry leading to alterations in genome regulation and mediating organism response to environmental transformations. Adverse environmental exposure can induce aberrant DNA methylation changes conducive to genetic dysfunction and, eventually, various pathologies. In recent years, evidence was derived that apart from 5-methylcytosine, the DNA methylation/demethylation cycle includes three other oxidative derivatives of cytosine—5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. 5hmC is a predominantly stable form and serves as both an intermediate product of active DNA demethylation and an essential hallmark of epigenetic gene regulation. This makes 5hmC a potential contributor to epigenetically mediated responses to environmental factors. In this state-of-the-art review, we consolidate the latest findings on environmentally induced adverse effects on 5hmC patterns in mammalian genomes. Types of environmental exposure under consideration include hypnotic drugs and medicines (i.e., phenobarbital, diethylstilbestrol, cocaine, methamphetamine, ethanol, dimethyl sulfoxide), as well as anthropogenic pollutants (i.e., heavy metals, particulate air pollution, bisphenol A, hydroquinone, and pentachlorophenol metabolites). We put a special focus on the discussion of molecular mechanisms underlying environmentally induced alterations in DNA hydroxymethylation patterns and their impact on genetic dysfunction. We conclude that DNA hydroxymethylation is a sensitive biosensor for many harmful environmental factors each of which specifically targets 5hmC in different organs, cell types, and DNA sequences and induces its changes through a specific metabolic pathway. The associated transcriptional changes suggest that environmentally induced 5hmC alterations play a role in epigenetically mediated genome flexibility. We believe that knowledge accumulated in this review together with further studies will provide a solid basis for new approaches to epigenetic therapy and chemoprevention of environmentally induced epigenetic toxicity involving 5hmC patterns.


title: The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future

text: The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.


title: Diffuse Alveolar Damage (DAD) from Coronavirus Disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

text: AIMS: Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID‐19)‐related deaths, but recent reports also describe additional atypical findings, including vascular changes. Here, we assess lung autopsy findings in COVID‐19 inpatients and untreated, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive individuals who died in the community to understand the relative impact of medical intervention on lung histology. Additionally, we investigate if COVID‐19 represents a unique histologic variant of DAD by comparing the pathologic findings to uninfected control patients. METHODS AND RESULTS: Lung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included 4 COVID‐19 inpatients, 4 cases with post‐mortem SARS‐CoV‐2 diagnoses who died in the community, and 8 SARS‐CoV‐2‐negative control cases. DAD was present in all but one SARS‐CoV‐2‐positive patient who was asymptomatic and died in the community. Although SARS‐CoV‐2‐positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organization, and “acute fibrinous and organizing pneumonia”‐like intraalveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, hemorrhage, and capillaritis were not features of COVID‐19‐related DAD. CONCLUSIONS: DAD is the primary histologic manifestation of severe lung disease in COVID‐19 patients who die both in the hospital and in the community, suggesting no contribution of hyperoxemic mechanical ventilation to the histologic changes. There are no distinctive morphologic features to confidently differentiate COVID‐19‐related DAD from DAD due to other causes.


An Example of Employing the Principles of Bioethics to Medical Decision Making in the COVID‐19 Era


title: Sustainability appraisal in infrastructure projects (SUSAIP) Part 1. Development of indicators and computational methods

text: Abstract The process of translating strategic sustainability objectives into concrete action at project-specific levels is a difficult task. The multi-dimensional perspectives of sustainability such as economy, society, environment, combined with a lack of structured methodology and information at various hierarchical levels, further exacerbate the problem. This paper (Part 1 of a two-part series) proposes an analytical decision model and a structured methodology for sustainability appraisal in infrastructure projects. The paper uses the ‘weighted sum model’ technique in multi-criteria decision analysis (MCDA) and the ‘additive utility model’ in analytical hierarchical process (AHP) for multi-criteria decision making, to develop the model from first principles. It discusses the development of key performance indicators encapsulated within the analytical model. It concludes by discussing other potential applications of the proposed model and methodology for process automation as part of integrated sustainability appraisal in infrastructure design and construction. Part 2 uses a case study to demonstrate the model application in infrastructure sustainability appraisal at design stages. The paper also discusses the challenges for sustainability research, and gives recommendations.


title: Big city, small world: density, contact rates, and transmission of dengue across Pakistan

text: Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e. each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of ‘mixing parameters’ when disaggregating data across an urban–rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions. We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof.


title: A distance learning enzyme assay and kinetics laboratory in the time of COVID‐19

text: This article describes a straightforward approach to deliver an enzyme assay and kinetics laboratory via online delivery methods in the time of COVID‐19.


title: The role of IL-29 in immunity and cancer

text: Abstract Interleukin-29 (IL-29) is a new member of the recently discovered interferon λ (IFNλ) family. It is produced predominantly by maturing dendritic cells and macrophages. It has been implicated in numerous immunological responses and has shown antiviral activity similar to the Type I interferons, although its target cell population is more limited than the Type I interferons. In recent years, the role of IL-29 in the pathogenesis of various cancers has also been extensively studied. In this review, we will discuss the recent advances of IL-29 in immunological processes and the pathogenesis of various cancer.


Does a cell protein explain covid-19 severity?


Feline models of viral pathogenesis: Opportunity knocks


title: Influenza epidemiology among hospitalized children in Stockholm, Sweden 1998–2014

text: BACKGROUND: Influenza remains a common reason for the hospitalization of children. There is a need for long term studies that are also population based. We describe the epidemiology of severe influenza in a defined population 1998–2014. METHOD: Retrospective study of annually collected data of virologically confirmed influenza in hospitalized children 0–17 years living in the catchment area (230,000 children). We gathered information about comorbidity and complications from case records, and compared Influenza A, B and A(H1N1)pdm09 with respect to these factors. RESULTS: A total of 922 children with influenza were hospitalized. The mean rate remained unchanged at 22.5–24.2 per 100,000 children per year. There were two major outbreaks: influenza A(H3N2) in 2003–2004 and the A(H1N1) pandemic in 2009–2010. The proportion of children with influenza B increased from 8% during the first half of the study period to 28% during the second half. The highest admission rate was found in children <3 months of age, 169 per 100,000. Children with influenza B were older than those with influenza A. Comorbidity was found in 34%, complications in 41%, and 11% needed intensive care management. The mortality rate was 0.17/100,000 children. CONCLUSION: Influenza remains an important reason for the hospitalization of children, especially during the first years of life. The increasing proportion of influenza B may have to be considered when recommending influenza vaccines.


title: Kinetics of the in vitro antibody response to transmissible gastroenteritis (TGE) virus from pig mesenteric lymph node cells, using the ELISASPOT and ELISA tests

text: Abstract A method is described for in vitro studies of viral humoral immune responses in the pig. After oral immunization with transmissible gastroenteritis (TGE) coronavirus, antibody production from primed mesenteric lymph node cells was revealed by an in vitro boost with viral antigen. For the latter the leukocytes were co-cultured with UV-inactivated virus using a variety of different methods of antigenic stimulation. Enumeration of specific antibody-secreting cells (ASC) and titration of secreted anti-virus antibodies were performed with ELISASPOT (using 3-amino 9-ethyl carbazole as the peroxidase chromogen) and ELISA tests respectively, according to the Ig isotype. The results showed a close relationship between ASC numbers and secreted antibody titres. The best in vitro antibody synthesis was observed when the sensitized cells were maintained in contact with virus during the whole culture period. Antibody responses were defined by a kinetic profile characterized by a narrow peak, with a maximum occuring after 4 and 6 days of culture and with the IgA response appearing earlier than the IgG. This methodology, which analyses specific antibody responses at the cellular level, may permit studies on the mechanisms of Ig isotype regulation. Extended to leukocytes from other organs of the immune system, it may also constitute an in vitro model to study antibody responses expressed in different lymphoid tissues of the pig.


Letter to the Editor in Response to article: “Clinical considerations for patients with diabetes in times of COVID-19 epidemic (Gupta et al.)


title: Using Problem-based Learning for Pandemic Preparedness

text: To test the hypothesis that PBL is an effective method for preparing multidisciplinary learner groups at community health centers (CHCs) for pandemics, quantitative and qualitative methods were utilized to evaluate the conduct of a PBL case of a hypothetical outbreak of severe acute respiratory syndrome (SARS) at two CHCs in Hawaii, with multidisciplinary health professional and student participants. It was found that: (1) there was an overall increase in knowledge of bioevent preparedness; (2) participants gave high ratings for the effectiveness of the PBL process; (3) participants found value in the multidisciplinary group process; and (4) participants strongly agreed that they preferred the PBL process to the traditional lecture format for learning about bioevent preparedness. The PBL approach is useful in educating community-based health professionals from different disciplines about issues related to pandemic preparedness.


title: Detection of antibodies against SARS‐CoV‐2 in patients with COVID‐19

text: Detection of IgM and IgG against SARS-CoV-2 is a fast and simple screening method. As an effective supplement to RNA testing, antibody detection is of epidemiological significance and an important means to understand the occurrence, development, prognosis, and outcome of COVID-19. However, more medical research is needed on the expression level of antibodies against SARS-CoV-2 and the prognosis of COVID-19. This article is protected by copyright. All rights reserved.