title: Neumonías bacterianas no neumocócicas (II). Infecciones respiratorias por Mycoplasma y Chlamydia. Neumonías víricas

text: Resumen Las neumonías no neumocócicas y víricas se incluyen en el grupo denominado neumonías atípicas. Son causadas por un amplio grupo de bacterias y virus, no obteniéndose en la mayoría de los casos el diagnóstico etiológico. Con frecuencia su presentación suele ser leve, aunque se han descrito casos fatales, principalmente en pacientes inmunocomprometidos. En ocasiones asocian clínica extrapulmonar dificultando su diagnóstico. Las pruebas microbiológicas no están indicadas en su diagnóstico, salvo en los casos de fracaso terapéutico o ante la necesidad de hospitalización del paciente. El tratamiento antibiótico empírico precoz debe iniciarse lo antes posible, puesto que esta medida ha demostrado disminuir la morbimortalidad. Las modificaciones en el mismo o la indicación de tratamiento antivírico asociado solo se realizan según la evolución clínica o la gravedad de la presentación. Otros tratamientos como la corticoterapia continúan siendo controvertidos. Abstract Non-pneumococcal and viral pneumonias are included in the group termed atypical pneumonias. They are caused by a wide range of bacteria and viruses; in most cases an aetiological diagnosis is not reached. Their clinical presentation is usually mild, although fatal cases have been described, principally in immunocompromised patients. Occasionally, extrapulmonary symptoms are associated, which makes diagnosis difficult. Microbiological tests are not indicated for diagnosis, except in the event of therapeutic failure or if the patient needs to be hospitalised. Early, empirical antibiotic treatment should be started as promptly as possible, since this has proven to reduce morbidity and mortality. Modifications to the treatment or associated viral treatment are only indicated according to the clinical progression or severity of the disease. Other treatments, such as corticotherapy, remain controversial.


title: Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences

text: Predicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.


title: Global Critical Care: Moving Forward in Resource-Limited Settings

text: Caring for critically ill patients is challenging in resource-limited settings, where the burden of disease and mortality from potentially treatable illnesses is higher than in resource-rich areas. Barriers to delivering quality critical care in these settings include lack of epidemiologic data and context-specific evidence for medical decision-making, deficiencies in health systems organization and resources, and institutional obstacles to implementation of life-saving interventions. Potential solutions include the development of common definitions for intensive care unit (ICU), intensivist, and intensive care to create a universal ICU organization framework; development of educational programs for capacity building of health care professionals working in resource-limited settings; global prioritization of epidemiologic and clinical research in resource-limited settings to conduct timely and ethical studies in response to emerging threats; adaptation of international guidelines to promote implementation of evidence-based care; and strengthening of health systems that integrates these interventions. This manuscript reviews the field of global critical care, barriers to safe high-quality care, and potential solutions to existing challenges. We also suggest a roadmap for improving the treatment of critically ill patients in resource-limited settings.


title: Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity

text: Abstract Effective global control of tuberculosis (TB) is increasingly threatened by the convergence of multidrug-resistant TB and the human immunodeficiency virus (HIV) infection. TB/HIV coinfections exert a tremendous burden on the host's immune system, and this has prompted the clinical use of immunomodulators to enhance host defences as an alternative therapeutic strategy. In this study, we modified the clinically used synthetic immunomodulatory pentapeptide, thymopentin (TP-5, RKDVY), with six arginine residues (RR-6, RRRRRR) at the N- and C-termini to obtain the cationic peptides, RR-11 (RKDVYRRRRRR-NH2) and RY-11 (RRRRRRRKDVY-NH2), respectively. The arginine residues conferred anti-mycobacterial activity to TP-5 in the peptides as shown by effective minimum inhibitory concentrations of 125 mg/L and killing efficiencies of >99.99% against both rifampicin-susceptible and -resistant Mycobacterium smegmatis. The immunomodulatory action of the peptides remained unaffected as shown by their ability to stimulate TNF-α production in RAW 264.7 mouse macrophage cells. A distinct change in surface morphology after peptide treatment was observed in scanning electron micrographs, while confocal microscopy and dye leakage studies suggested bacterial membrane disruption by the modified peptides. The modified peptides were non-toxic and did not cause hemolysis of rat red blood cells up to a concentration of 2000 mg/L. Moreover, RY-11 showed synergism with rifampicin and reduced the effective concentration of rifampicin, while preventing the induction of rifampicin resistance. The synthetic peptides may have a potential application in both immunocompetent and immunocompromised TB patients.


title: Identification of one peptide which inhibited infectivity of avian infectious bronchitis virus in vitro

text: Purified avian infectious bronchitis virus (IBV) was used to screen a random phage display peptide library. After the fourth panning, 10 positive phages were sequenced and characterized. The phages specifically inhibited IBV infectivity in HeLa cells and blocked IBV haemagglutination. One linear peptide “GSH HRH VHS PFV” from the positive phages with the highest neutralization titer was synthesized and this peptide inhibited IBV infection in HeLa as well. The results may contribute to development of antiviral therapeutics for IBV and studying the determinants for viral and cell interaction.


title: Innovations in HIV-1 Vaccine Design

text: Abstract Purpose The field of HIV-1 vaccinology has evolved during the last 30 years from the first viral vector HIV gene insert constructs to vaccination regimens using a myriad of strategies. These strategies now include germline-targeting, lineage-based, and structure-guided immunogen design. This narrative review outlines the historical context of HIV vaccinology and subsequently highlights the scientific discoveries during the last 6 years that promise to propel the field forward. Methods We conducted a search of 2 electronic databases, PubMed and EMBASE, for experimental studies that involved new HIV immunogen designs between 2013 and 2019. During the title and abstract reviews, publications were excluded if they were written in language other than English and/or were a letter to the editor, a commentary, or a conference-only presentation. We then used ClinicalTrials.gov to identify completed and ongoing clinical trials using these strategies. Findings The HIV vaccinology field has undergone periods of significant growth during the last 3 decades. Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system. As a result, several new rationally designed vaccine strategies have been developed and explored in the last 6 years, including native-like envelope trimers, nanoparticle, and mRNA vaccine design strategies among others. Several of these strategies have shown enough promise in animal models to progress toward first-in-human Phase I clinical trials. Implications Rapid developments in preclinical and early-phase clinical studies suggest that a tolerable and effective HIV vaccine may be on the horizon.


title: Seasonal and Pandemic A (H1N1) 2009 influenza vaccination coverage and attitudes among health-care workers in a Spanish University Hospital

text: Influenza vaccination coverage among health-care workers (HCWs) remains the lowest compared with other priority groups for immunization. Little is known about the acceptability and compliance with the pandemic (H1N1) 2009 influenza vaccine among HCWs during the current campaign. Between 23 December 2009 and 13 January 2010, once the workplace vaccination program was over, we conducted a cross-sectional, questionnaire-based survey at the University Hospital 12 de Octubre (Madrid, Spain). Five hundred twenty-seven HCWs were asked about their influenza immunization history during the 2009–2010 season, as well as the reasons for accepting or declining either the seasonal or pandemic vaccines. Multiple logistic-regression analysis was preformed to identify variables associated with immunization acceptance. A total of 262 HCWs (49.7%) reported having received the seasonal vaccine, while only 87 (16.5%) affirmed having received the pandemic influenza (H1N1) 2009 vaccine. “Self-protection” and “protection of the patient” were the most frequently adduced reasons for acceptance of the pandemic vaccination, whereas the existence of “doubts about vaccine efficacy” and “fear of adverse reactions” were the main arguments for refusal. Simultaneous receipt of the seasonal vaccine (odds ratio [OR]: 0.27; 95% confidence interval [95% CI]: 0.14–0.52) and being a staff (OR: 0.08; 95% CI: 0.04–0.19) or a resident physician (OR: 0.16; 95% CI: 0.05–0.50) emerged as independent predictors for pandemic vaccine acceptance, whereas self-reported membership of a priority group was associated with refusal (OR: 5.98; 95% CI: 1.35–26.5). The pandemic (H1N1) 2009 influenza vaccination coverage among the HCWs in our institution was very low (16.5%), suggesting the role of specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario.


title: The pathogenesis of nephritis in chickens induced by infectious bronchitis virus

text: Abstract Nephritis in chickens caused by infectious bronchitis virus (IBV) was studied by virological, histological and electron microscopical methods. The T strain of the virus caused only mild respiratory signs in both Rhode Island Red (RIR) and White Leghorn (WL) breeds; the 50 per cent mortality induced was due to acute nephritis. All the infected birds developed high titres of antibody to IBV for up to 30 weeks. In spite of the persistence of antibody, about 35 per cent of the RIR developed chronic progressive nephritis. The histology showed varying degrees of pathological changes in the tubules, with relatively unaffected glomeruli. Foci of mononuclear cell infiltration were prominent in the cortex and medulla, particularly in chronic nephritis. Cytoplasmic IBV immunofluorescence was found in all segments of the tubules, but not in the glomeruli. There was no evidence of virus replication in the caecal tonsil and bursa of Fabricius. Evidence of extensive coronavirus replication was found in the cells of the tubules. A large number of viral inclusion bodies as seen containing dark smooth particles 120 nm in diameter within a single membrane. Virus was readily recovered from the kidneys as well as faeces of birds with acute and chronic nephritis. It is concluded that direct virus-induced cell lysis is the primary cause of IBV nephritis. In addition, about 50 per cent of the chronically infected birds also developed brush-border auto-antibody.


title: Collateral Damage of the COVID‐19 Pandemic on Nutritional Quality and Physical Activity: Perspective from South Korea

text: A novel coronavirus (SARS‐CoV‐2), that emerged in the city of Wuhan, China in December 2019, has now spread worldwide.


title: COVID‐19: Herd Immunity and Convalescent Plasma Transfer Therapy

text: Coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has spread worldwide triggering a pandemic. Its first case was reported in Wuhan, the capital of China's Hubei province, and since then it has spread across world becoming one of the worst pandemics in the history of mankind(1). Its basic reproductive number (R(0)) has been determined to be 2‐3(2). This article is protected by copyright. All rights reserved.


title: The impact of COVID-19 as a necessary evil on air pollution in India during the lockdown()

text: The study objective is to contemplate the effectiveness of COVID-19 on the air pollution of Indian territory from January 2020 to April 2020. We have executed data from European Space Agency (ESA) and CPCB online portal for air quality data dissemination. The Sentinel – 5 P satellite images elucidate that the Air quality of Indian territory has been improved significantly during COVID-19. Mumbai and Delhi are one of the most populated cities. These two cities have observed a substantial decrease in Nitrogen Dioxide (40–50%) compared to the same period last year. It suggests that the emergence of COVID-19 has been proved to a necessary evil as being advantageous for mitigating air pollution on Indian territory during the lock-down. The study found a significant decline in Nitrogen Dioxide in reputed states of India, i.e., Delhi and Mumbai. Moreover, a faded track of Nitrogen Dioxide can be seen at the Maritime route in the Indian Ocean. An upsurge in the environmental quality of India will also be beneficial for its neighbor countries, i.e., China, Pakistan, Iran, and Afghanistan.


title: Temporal rise in the proportion of both younger adults and older adolescents among COVID-19 cases in Germany: evidence of lesser adherence to social distancing practices?

text: BACKGROUND: There is uncertainty about the role of different age groups in propagating the SARS-CoV-2 epidemics in different countries, particularly under current social distancing practices. METHODS: We used the Robert Koch Institute data on weekly COVID-19 cases in different age groups in Germany. To minimize the effect of changes in healthcare seeking behavior (e.g. for older adults) and testing practices, we included the following eight 5-year age groups in the analyses: 10–14y through 45–49y. For each age group g, we considered the proportion PL(g) of individuals in age group g among all detected cases aged 10–49y during weeks 13–14, 2020 (later period), as well as corresponding proportion PE(g) for weeks 10–11, 2020 (early period), and defined the relative risk RR(g) for the age group g to be the ratio RR(g) = PL(g)/PE(g). For each pair of age groups g1, g2, a higher value of RR(g1) compared to RR(g2), or, alternatively, a value above 1 for the odds ratio OR(g1, g2) = RR(g1)/RR(g2) for a COVID-19 case to be in group g1 vs. g2 for the later vs. early periods is interpreted as the relative increase in the population incidence of SARS-Cov-2 in the age group g1 compared to g2 for the later vs. early period. RESULTS: The relative risk RR(g) was highest for individuals aged 20–24y (RR=1.4(95% CI (1.27,1.55))), followed by individuals aged 15–19y (RR=1.14(0.99,1.32)), aged 30–34y (RR=1.07(0.99,1.16)), aged 25–29y (RR= 1.06(0.98,1.15)), aged 35–39y (RR=0.95(0.87,1.03)), aged 40–44y (RR=0.9(0.83,0.98)), aged 45–49y (RR=0.83(0.77,0.89)) and aged 10–14y (RR=0.78(0.64,0.95)). For the age group 20–24y, the odds ratio relative to any other age group for a case to be during the later vs. early period was significantly above 1. For the age group 15–19y, the odds ratio relative to any other age group either above 35y or 10–14y for a case to be during the later vs. early period was significantly above 1. CONCLUSIONS: The observed relative increase with time in the prevalence of individuals aged 15–34y (particularly those aged 20–24y) among detected COVID-19 cases in Germany is unlikely to be explained by increases in the likelihood of seeking medical care or the likelihood of being tested for individuals in those age groups compared to individuals aged 35–49y or 10–14y, and should be indicative of the actual increase in the prevalence of individuals aged 15–34y among SARS-CoV-2 infections in the German population. That increase likely reflects elevated mixing among individuals aged 15–34y (particularly those aged 20–24y) compared to other age groups, possibly due to lesser adherence to social distancing practices.


title: Design for Implementation of a System-Level ICU Pandemic Surge Staffing Plan

text: BACKGROUND: The current coronavirus disease 2019 pandemic is causing significant strain on ICUs worldwide. Initial and subsequent regional surges are expected to persist for months and potentially beyond. As a result of this, as well as the fact that ICU provider staffing throughout the United States currently operate at or near capacity, the risk for severe and augmented disruption in delivery of care is very real. Thus, there is a pressing need for proactive planning for ICU staffing augmentation, which can be implemented in response to a local surge in ICU volumes. METHODS: We provide a description of the design, dissemination, and implementation of an ICU surge provider staffing algorithm, focusing on physicians, advanced practice providers, and certified registered nurse anesthetists at a system-wide level. RESULTS: The protocol was designed and implemented by the University of Pittsburgh Medical Center’s Integrated ICU Service Center and was rolled out to the entire health system, a 40-hospital system spanning Pennsylvania, New York, and Maryland. Surge staffing models were developed using this framework to assure that local needs were balanced with system resource supply, with rapid enhancement and expansion of tele-ICU capabilities. CONCLUSIONS: The ICU pandemic surge staffing algorithm, using a tiered-provider strategy, was able to be used by hospitals ranging from rural community to tertiary/quaternary academic medical centers and adapted to meet specific needs rapidly. The concepts and general steps described herein may serve as a framework for hospital and other hospital systems to maintain staffing preparedness in the face of any form of acute patient volume surge.


title: Poxvirus Exploitation of the Ubiquitin-Proteasome System

text: Ubiquitination plays a critical role in many cellular processes. A growing number of viruses have evolved strategies to exploit the ubiquitin-proteasome system, including members of the Poxviridae family. Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Multiple members of the poxvirus family also encode ubiquitin ligases with intrinsic activity. This review describes the numerous mechanisms that poxviruses employ to manipulate the ubiquitin-proteasome system.


title: Bat tolerance to viral infections

text: Inflammatory molecules evolved partly to protect hosts from viruses, but increasing evidence suggests that they cause disease pathology and chronic conditions, and play a role in aging. By mitigating these effects, bats are able to both tolerate viral infections and live well beyond expectations.


title: Enveloped Virus but not Bacteria Block IL‐13 Responses in Human Cord Blood T Cells In Vitro

text: Infections that occur early in life may have a beneficial effect on the immune system and thereby reduce the risk of allergen sensitization and/or allergic disease. It is not yet clear to what extent specific virus and/or bacteria can mediate this effect. The purpose of this study was to assess the role of virus and bacteria in CD4(+) T cell‐derived cytokine production in newborns. We compared the effects of five bacteria (Staphlococcus aureus, Escherichia coli, Clostridium difficile, Lactobacillus rhamnosus and Bifidobacterium bifidus) and seven virus (adenovirus, coronavirus, cytomegalovirus, herpes simplex virus, influenza virus, morbillivirus and poliovirus) on the Th1/Th2 cytokine production in mixed lymphocyte reactions using CD4(+) T cells from cord blood cocultured with allogenic myeloid or plasmacytoid dendritic cells. When comparing the baseline cytokine production prior to microbial stimulation, we observed that cord plasmacytoid DC were stronger inducers of Th2 cytokines (IL‐5 and IL‐13) compared with cord myeloid DC and to adult DC. When adding microbes to these cultures, bacteria and virus differed in two major respects; Firstly, all enveloped viruses, but none of the bacteria, blocked Th2 (IL‐13) production by cord CD4(+) cells. Secondly, all Gram‐positive bacteria, but none of the virus, induced IL‐12p40 responses, but the IL‐12p40 responses did not affect Th1 cytokine production (IFN‐γ). Instead, Th1 responses were correlated with the capacity to induce IFN‐α secretion, which in cord cells were induced by S. aureus and influenza virus alone. These data imply that enveloped virus can deviate Th2 responses in human cord T cells.


title: Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

text: Abstract Infectious disease control and prevention relies on a thorough understanding of the factors determining transmission. This article summarizes the fundamental principles of infectious disease transmission while highlighting many of the agent, host, and environmental determinants of these diseases that are of particular import to public health professionals. Basic principles of infectious disease diagnosis, control, and prevention are also reviewed.


title: Rapid detection of the common avian leukosis virus subgroups by real-time loop-mediated isothermal amplification

text: BACKGROUND: Subgroups A, B, E and J are the major subgroups of avian leukosis virus (ALV) infecting chickens. ALV infection has become endemic in China and has a significant negative effect on the poultry industry. Consequently, there is an urgent need for a specific, sensitive and rapid method for diagnosis and eradication of ALV. Therefore, we developed a simple and rapid real-time loop-mediated isothermal amplification (LAMP) reaction for the timely detection of the common ALV subgroups, whereby the amplification can be obtained in 35 min under isothermal conditions at 63 °C, ability to specific, sensitive and rapid detect all the common ALV subgroups. METHODS: A set of four specific primers was designed to target the sequences of the pol gene of ALV, and the loop-mediated isothermal amplification (LAMP) assay were developed and compared with PCR and virus isolation methods. RESULTS: The results from specificity of the LAMP assay showed that only target ALVs DNA was amplified. The LAMP assay demonstrated a sensitivity of 20 copies/reaction of ALV DNA, which was 10 times higher than the conventional PCR measurement. To further evaluate the reliability of the method, the assay was evaluated with ALV DNA from a panel of 81 clinical samples suspected of ALV infection. The results verify that the LAMP method was more sensitive than the conventional PCR and virus isolation method. CONCLUSION: In conclusion, the developed LAMP assay was a simple, inexpensive, sensitive method for the rapid detection of the most common subgroups of ALV, and it provided a useful and practical tool in the eradication program for ALV in the poultry industry.


title: Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia

text: Background. The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear. Methods. We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs). Results. We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5–0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77). Conclusions. The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.


title: Association Between Hypoxemia and Mortality in Patients With COVID-19

text: Abstract Objective To identify markers associated with in-hospital death in patients with Coronavirus Disease 2019 (COVID-19) associated pneumonia. Patients and Methods Retrospective, cohort study of 140 patients with moderate-to-critical COVID-19 associated pneumonia requiring oxygen supplementation admitted from January 28th, 2020 to February 28th, 2020, and followed up through March, 13th 2020 in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis. Results Of 140 patients with COVID-19 associated pneumonia, 51.4% were men, with a median age of 60 years. Patients with SpO2 ≤90% were older, more likely to be men, to have hypertension and to present with dyspnea than those with SpO2 >90%. Overall, 36 (25.7%) patients died during hospitalization after a median 14-day follow-up. Higher post-oxygen supplementation SpO2 levels were associated with reduced mortality independently of age and sex (hazard ratio per 1-unit SpO2 0.93, 95% confidence interval, 0.91-0.95, P < .001). SpO2 cutoff of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio 2.60; 95% confidence interval 1.24-5.43, P = .01). Conclusions In this cohort of COVID-19 patients, hypoxemia was independently associated with in-hospital mortality. These results may help guide clinical management of severe COVID-19 patients, particularly in settings requiring strategic allocation of limited critical care resources.


title: Recombinant expression of nanobodies and nanobody-derived immunoreagents

text: Abstract Antibody fragments for which the sequence is available are suitable for straightforward engineering and expression in both eukaryotic and prokaryotic systems. When produced as fusions with convenient tags, they become reagents which pair their selective binding capacity to an orthogonal function. Several kinds of immunoreagents composed by nanobodies and either large proteins or short sequences have been designed for providing inexpensive ready-to-use biological tools. The possibility to choose among alternative expression strategies is critical because the fusion moieties might require specific conditions for correct folding or post-translational modifications. In the case of nanobody production, the trend is towards simpler but reliable (bacterial) methods that can substitute for more cumbersome processes requiring the use of eukaryotic systems. The use of these will not disappear, but will be restricted to those cases in which the final immunoconstructs must have features that cannot be obtained in prokaryotic cells. At the same time, bacterial expression has evolved from the conventional procedure which considered exclusively the nanobody and nanobody-fusion accumulation in the periplasm. Several reports show the advantage of cytoplasmic expression, surface-display and secretion for at least some applications. Finally, there is an increasing interest to use as a model the short nanobody sequence for the development of in silico methodologies aimed at optimizing the yields, stability and affinity of recombinant antibodies.


The health and socioeconomic impact on menopausal women of working from home


title: Surface display of proteins by Gram-negative bacterial autotransporters

text: Expressing proteins of interest as fusions to proteins of the bacterial envelope is a powerful technique with many biotechnological and medical applications. Autotransporters have recently emerged as a good tool for bacterial surface display. These proteins are composed of an N-terminal signal peptide, followed by a passenger domain and a translocator domain that mediates the outer membrane translocation of the passenger. The natural passenger domain of autotransporters can be replaced by heterologous proteins that become displayed at the bacterial surface by the translocator domain. The simplicity and versatility of this system has made it very attractive and it has been used to display functional enzymes, vaccine antigens as well as polypeptides libraries. The recent advances in the study of the translocation mechanism of autotransporters have raised several controversial issues with implications for their use as display systems. These issues include the requirement for the displayed polypeptides to remain in a translocation-competent state in the periplasm, the requirement for specific signal sequences and "autochaperone" domains, and the influence of the genetic background of the expression host strain. It is therefore important to better understand the mechanism of translocation of autotransporters in order to employ them to their full potential. This review will focus on the recent advances in the study of the translocation mechanism of autotransporters and describe practical considerations regarding their use for bacterial surface display.


title: Molecular Epidemiology of Canine Parvovirus, Europe

text: Canine parvovirus (CPV), which causes hemorrhagic enteritis in dogs, has 3 antigenic variants: types 2a, 2b, and 2c. Molecular method assessment of the distribution of the CPV variants in Europe showed that the new variant CPV-2c is widespread in Europe and that the viruses are distributed in different countries.


title: Epidemiology and microbiological investigations of community-acquired pneumonia in children admitted at the emergency department of a university hospital

text: Abstract Background The management of children with community-acquired pneumonia (CAP) is largely influenced by the development of new molecular diagnostic tests that allow the simultaneous detection of a wide range of pathogens. Objectives Evaluation of a diagnostic approach including multiplex PCR assays for revisiting the epidemiology and etiology of CAP in children at hospital. Study design Children of all ages consulting at the Emergency Department of the University hospital of Saint-Etienne, France, during the 2012–2013 winter period were included. In addition to bacterial cultures, the following pathogens were detected using biplex commercially-available rt-PCR tests: adenovirus, respiratory syncytial virus, human metapneumovirus, bocavirus, rhinovirus/enterovirus, coronavirus, influenza viruses A and B, parainfluenza viruses, Mycoplasma pneumoniae and Chlamydophila pneumonia. Results From 85 patients with CAP, at least one pathogen was identified in 81 cases (95.3%), including 4 bacterial exclusive infections (4.7%), 53 viral exclusive infections (62.4%) and 24 mixed infections (28.2%). Coinfection by at least two viruses was observed in 37 cases (43.5%). Mean age was higher in the case of documented bacterial infection (P <0.05). In the subgroup of viral exclusive infection, the mean age of severe cases was 2.0 years vs 3.8 years in mild and moderate cases (P <0.05). Conclusions These findings highlight the huge proportion of CAP of viral origin, the high number of co-infection by multiple viruses and the low number of bacterial CAP, notably in children under 5 years, and address the need to re-evaluate the indications of empiric antimicrobial treatment in this age group.


title: Viral load in patients infected with pandemic H1N1 2009 influenza A virus

text: Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre‐treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty‐two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 × 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 × 10(8) copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT‐PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1–7, 2010. © 2009 Wiley‐Liss, Inc.


Need for Innovative and Timely Synthesis of Evidence during Covid-19 outbreak


title: A Markov chain model for predicting transient particle transport in enclosed environments

text: Abstract Obtaining information about particle dispersion in a room is crucial in reducing the risk of infectious disease transmission among occupants. This study developed a Markov chain model for quickly obtaining the information on the basis of a steady-state flow field calculated by computational fluid dynamics. When solving the particle transport equations, the Markov chain model does not require iterations in each time step, and thus it can significantly reduce the computing cost. This study used two sets of experimental data for transient particle transport to validate the model. In general, the trends in the particle concentration distributions predicted by the Markov chain model agreed reasonably well with the experimental data. This investigation also applied the model to the calculation of person-to-person particle transport in a ventilated room. The Markov chain model produced similar results to those of the Lagrangian and Eulerian models, while the speed of calculation increased by 8.0 and 6.3 times, respectively, in comparison to the latter two models.


title: Clinical and immunologic studies in identical twins discordant for systemic lupus erythematosus

text: Abstract Middle-aged female identical twins, one of whom had systemic lupus erythematosus (SLE), were evaluated for immunologic reactivity to previous antigenic challenges, including primary immunization with a foreign antigen, keyhole limpet hemocyanin (KLH). These two women had lived together for all of their 58 years and neither was receiving anti-inflammatory or immunosuppressive drugs at the time of these studies. Both twins demonstrated comparable 7S and 198 humoral antibody response to KLH, as well as similar viral antibody titers. However, the twin with SLE was anergic to common antigens, streptokinase-streptodornase, Trichophyton and Candida; furthermore delayed hypersensitivity to KLH did not develop after immunization. This observed discrepancy between humoral and cellular immunity in genetically similar subjects may be significant in the pathogenesis of SLE.


title: Laboratory biosafety for handling emerging viruses

text: Abstract Emerging viruses are viruses whose occurrence has risen within the past twenty years, or whose presence is likely to increase in the near future. Diseases caused by emerging viruses are a major threat to global public health. In spite of greater awareness of safety and containment procedures, the handling of pathogenic viruses remains a likely source of infection, and mortality, among laboratory workers. There is a steady increase in both the number of laboratories and scientist handling emerging viruses for diagnostics and research. The potential for harm associated to work with these infectious agents can be minimized through the application of sound biosafety concepts and practices. The main factors to the prevention of laboratory-acquired infection are well-trained personnel who are knowledgable and biohazard aware, who are perceptive of the various ways of transmission, and who are professional in safe laboratory practice management. In addition, we should emphasize that appropriate facilities, practices and procedures are to be used by the laboratory workers for the handling of emerging viruses in a safe and secure manner. This review is aimed at providing researchers and laboratory personnel with basic biosafety principles to protect themselves from exposure to emerging viruses while working in the laboratory. This paper focuses on what emerging viruses are, why emerging viruses can cause laboratory-acquired infection, how to assess the risk of working with emerging viruses, and how laboratory-acquired infection can be prevented. Control measures used in the laboratory designed as such that they protect workers from emerging viruses and safeguard the public through the safe disposal of infectious wastes are also addressed.


title: Israel Ad Hoc COVID‐19 Committee: Guidelines for Care of Older Persons During a Pandemic

text: Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID‐19). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long‐term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a “soft utilitarian” approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, “biological age” would enter into the triage considerations, but only in the case of distinguishing between people with equal non–age‐related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD‐19 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation.


title: Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China

text: Abstract Purpose To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. Results The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13% [41/46]) and air bronchogram (69.57% [32/46]) were found. Other ﬁndings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calciﬁcation or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45%). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients(28.57%). Conclusion The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible ﬁbrosis.


title: Amplification of viral RNA from drinking water using TransPlex™ whole‐transcriptome amplification

text: Aims: Viral pathogens in environmental media are generally highly diffuse, yet small quantities of pathogens may pose a health risk. This study evaluates the ability of TransPlex™ whole transcriptome amplification (WTA) to amplify small quantities of RNA viruses from complex environmental matrices containing background nucleic acids. Methods and Results: DNA extracts from mock drinking water samples containing mixed microbial populations were spiked with small quantities of echovirus type 13 (EV) RNA. Samples were amplified using a Transplex™ WTA kit, and EV‐specific quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to quantify target pathogens before and after application of WTA. Samples amplified by WTA demonstrated a decreased limit of detection. The log‐linear relationship between serial dilutions was maintained following amplification by WTA. Conclusions: WTA is able to increase the quantity of target organism RNA in mixed populations, while maintaining log linearity of amplification across different target concentrations. Significance and Impact of the Study: WTA may serve as an effective preamplification step to increase the levels of RNA prior to detection by other molecular methods such as PCR, microarrays and sequencing.


title: Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus

text: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (CoV), SARS-CoV. In previous studies, we showed that a SARS-CoV spike (S) glycoprotein-based modified vaccinia Ankara (MVA-S) vaccine could induce strong neutralizing antibody (Nab) response which might have played a critical role in protecting Chinese rhesus monkeys from the pathogenic viral challenge. To date, however, it remains unknown what the minimal level of Nab is required to achieve sterile immunity in humans. It is therefore important to explore techniques to maximize the level of Nab response in vivo. Here, we evaluate various vaccination regimens using combinations of DNA-S, MVA-S, and adenovirus type 5 (Ad5-S) vaccines. We show that in vaccinated mice and rabbits, a heterologous MVA-S prime with Ad5-S boost regimen induces the highest and most persistent level of Nab response when compared with other combinations. Interestingly, the initial level of Nab after prime does not necessarily predict the magnitude of the secondary response after the boost. Thus, our data provides a promising optimal regimen for vaccine development in humans against SARS-CoV infection.


title: Nonhomologous RNA Recombination in a Cell-Free System: Evidence for a Transesterification Mechanism Guided by Secondary Structure

text: Abstract Extensive nonhomologous recombinations occur between the 5′ and 3′ fragments of a replicable RNA in a cell-free system composed of pure Qβ phage replicase and ribonucleoside triphosphates, providing direct evidence for the ability of RNAs to recombine without DNA intermediates and in the absence of host cell proteins. The recombination events are revealed by the molecular colony technique that allows single RNA molecules to be cloned in vitro. The observed nonhomologous recombinations are entirely dependent on the 3′ hydroxyl group of the 5′ fragment, and are due to a splicing-like reaction in which RNA secondary structure guides the attack of this 3′ hydroxyl on phosphoester bonds within the 3′ fragment.


Covid-19 diffusion in a neurosurgical “clean” department: the asymptomatic Trojan horse


title: Proteome Analysis in a Mammalian Cell Line Reveals that PLK2 Is Involved in Avian Metapneumovirus Type C (aMPV/C)-Induced Apoptosis

text: Avian metapneumovirus subtype C (aMPV/C) causes an acute respiratory disease that has caused serious economic losses in the Chinese poultry industry. In the present study, we first explored the protein profile in aMPV/C-infected Vero cells using iTRAQ quantitative proteomics. A total of 921 of 7034 proteins were identified as significantly altered by aMPV/C infection. Three selected proteins were confirmed by Western blot analysis. Bioinformatics GO analysis revealed multiple signaling pathways involving cell cycle, endocytosis, and PI3K-Akt, mTOR, MAPK and p53 signaling pathways, which might participate in viral infection. In this analysis, we found that PLK2 expression was upregulated by aMPV/C infection and investigated whether it contributed to aMPV/C-mediated cellular dysfunction. Suppressing PLK2 attenuated aMPV/C-induced reactive oxygen species (ROS) production and p53-dependent apoptosis and reduced virus release. These results in a mammalian cell line suggest that high PLK2 expression correlates with aMPV/C-induced apoptosis and viral replication, providing new insight into the potential avian host cellular response to aMPV/C infection and antiviral targets.


title: How to Surge to Face the SARS-CoV-2 Outbreak: Lessons Learned From Lombardy, Italy

text: Italy is fighting against one of the worst medical emergency since the 1918 Spanish Flu. Pressure on the hospitals is tremendous. As for official data on March 14th: 8372 admitted in hospitals, 1518 in intensive care units, 1441 deaths (175 more than the day before). Unfortunately, hospitals are not prepared: even where a plan for massive influx of patients is present, it usually focuses on sudden onset disaster trauma victims (the most probable case scenario), and it has not been tested, validated, or propagated to the staff. Despite this, the All Hazards Approach for management of major incidents and disasters is still valid and the “4S” theory (staff, stuff, structure, systems) for surge capacity can be guidance to respond to this disaster.


title: The Microbiota of the Extremely Preterm Infant

text: Colonization of the extremely preterm infant’s gastrointestinal tract and skin begins in utero and is influenced by a variety of factors, the most important including gestational age and environmental exposures. The composition of the intestinal and skin microbiota influences the developing innate and adaptive immune responses with short-term and long-term consequences including altered risks for developing necrotizing enterocolitis, sepsis, and a wide variety of microbe-related diseases of children and adults. Alteration of the composition of the microbiota to decrease disease risk is particularly appealing for this ultra–high-risk cohort that is brand new from an evolutionary standpoint.


title: Risk-based surveillance for avian influenza control along poultry market chains in South China: The value of social network analysis

text: Abstract Over the past two decades, the poultry sector in China went through a phase of tremendous growth as well as rapid intensification and concentration. Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 was first detected in 1996 in Guangdong province, South China and started spreading throughout Asia in early 2004. Since then, control of the disease in China has relied heavily on wide-scale preventive vaccination combined with movement control, quarantine and stamping out. This strategy has been successful in drastically reducing the number of outbreaks during the past 5years. However, HPAIV H5N1 is still circulating and is regularly isolated in traditional live bird markets (LBMs) where viral infection can persist, which represent a public health hazard for people visiting them. The use of social network analysis in combination with epidemiological surveillance in South China has identified areas where the success of current strategies for HPAI control in the poultry production sector may benefit from better knowledge of poultry trading patterns and the LBM network configuration as well as their capacity for maintaining HPAIV H5N1 infection. We produced a set of LBM network maps and estimated the associated risk of HPAIV H5N1 within LBMs and along poultry market chains, providing new insights into how live poultry trade and infection are intertwined. More specifically, our study provides evidence that several biosecurity factors such as daily cage cleaning, daily cage disinfection or manure processing contribute to a reduction in HPAIV H5N1 presence in LBMs. Of significant importance is that the results of our study also show the association between social network indicators and the presence of HPAIV H5N1 in specific network configurations such as the one represented by the counties of origin of the birds traded in LBMs. This new information could be used to develop more targeted and effective control interventions.


title: Comparison of Serologic Assays for Middle East Respiratory Syndrome Coronavirus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in humans in 2012. Since then, sporadic outbreaks with primary transmission through dromedary camels to humans and outbreaks in healthcare settings have shown that MERS-CoV continues to pose a threat to human health. Several serologic assays for MERS-CoV have been developed globally. We describe a collaborative study to investigate the comparability of serologic assays for MERS-CoV and assess any benefit associated with the introduction of a standard reference reagent for MERS-CoV serology. Our study findings indicate that, when possible, laboratories should use a testing algorithm including >2 tests to ensure correct diagnosis of MERS-CoV. We also demonstrate that the use of a reference reagent greatly improves the agreement between assays, enabling more consistent and therefore more meaningful comparisons between results.


title: Time to get thrifty

text: Hyperconsumption is one of the things that got us into this mess. But we have to avoid the temptation to rely on it to get us out again, writes Graham Lawton


title: Estimation and prediction of COVID-19 cases in Brazilian metropolises

text: OBJECTIVE: to estimate the transmission rate, the epidemiological peak, and the number of deaths by the new coronavirus. METHOD: a mathematical and epidemiological model of susceptible, infected, and recovered cases was applied to the nine Brazilian capitals with the highest number of cases of the infection. The number of cases for the 80 days following the first case was estimated by solving the differential equations. The results were logarithmized and compared with the actual values to observe the model fit. In all scenarios, it was considered that no preventive measures had been taken. RESULTS: the nine metropolises studied showed an upward curve of confirmed cases of COVID-19. The prediction data point to the peak of the infection between late April and early May. Fortaleza and Manaus had the highest transmission rates (≥2·0 and ≥1·8, respectively). Rio de Janeiro may have the largest number of infected people (692,957) and Florianópolis the smallest (24,750). CONCLUSION: the estimates of the transmission rate, epidemiological peak, and number of deaths from coronavirus in Brazilian metropolises presented expressive and important numbers the Brazilian Ministry of Health needs to consider. The results confirm the rapid spread of the virus and its high mortality in the country.


title: Equine immunoglobulin F(ab')2 fragments protect cats against feline calicivirus infection

text: Abstract Feline calicivirus (FCV) causes upper respiratory tract infections in felines and threatens the health of wild and domestic felines. Clinically, specific drugs to treat FCV have not yet been developed. Here, IgG was extracted from inactivated FCV-immunized horse sera. Equine F(ab')2 fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. In our study, equine immunoglobulin F(ab')2 fragments showed efficient neutralizing activity in vitro against FCV and had therapeutic and prophylactic effects in FCV-infected cats. The anti-FCV-specific F(ab')2 fragment can significantly alleviate the clinical symptoms of FCV-infected cats and reduce the viral loads of the trachea, lung and spleen. These results indicate that the F(ab')2 fragment prepared from inactivated FCV-immunized horses may be used as a prophylactic and therapeutic agent for diseases caused by FCV.


A46 MERS-CoV in Arabian camels in Africa and Central Asia


title: Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold

text: BACKGROUND: The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. METHODS: In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. RESULTS: Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. CONCLUSIONS: Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.


title: Development of Human Single-Chain Antibodies against SARS-Associated Coronavirus

text: The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro.


title: FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation

text: BACKGROUND: Epithelial invagination is important for initiation of ectodermal organogenesis. Although many factors regulate ectodermal organogenesis, there is not any report about their functions in real-time study. Electric cell-substrate impedance sensing (ECIS), a non-invasive, real-time surveillance system, had been used to detect changes in organ cell layer thickness through quantitative monitoring of the impedance of a cell-to-microelectrode interface over time. It was shown to be a good method for identifying significant real-time changes of cells. The purpose of this study is to establish a combined bioengineered organ-ECIS model for investigating the real time effects of fibroblast growth factor-9 (FGF-9) on epithelial invagination in bioengineered ectodermal organs. We dissected epithelial and mesenchymal cells from stage E14.5 murine molar tooth germs and identified the real-time effects of FGF-9 on epithelial-mesenchymal interactions using this combined bioengineered organ-ECIS model. RESULTS: Measurement of bioengineered ectodermal organ thickness showed that Fibroblast growth factor-9 (FGF-9) accelerates epithelial invagination in reaggregated mesenchymal cell layer within 3 days. Gene expression analysis revealed that FGF-9 stimulates and sustains early Ameloblastin and Amelogenin expression during odontogenesis. CONCLUSIONS: This is the first real-time study to show that, FGF-9 plays an important role in epithelial invagination and initiates ectodermal organogenesis. Based on these findings, we suggest FGF-9 can be applied for further study in ectodermal organ regeneration, and we also proposed that the ‘FGF-BMP balancing system’ is important for manipulating the morphogenesis of ectodermal organs. The combined bioengineered organ-ECIS model is a promising method for ectodermal organ engineering and regeneration research.


title: Numerical simulation of virus diffusion in facemask during breathing cycles

text: Abstract The recent SARS outbreak has spawned a major controversy concerning the protective performance of facemasks. The objective of this paper is to establish a mathematical model for describing the mechanism of viruses diffusion in a facemask during breathing cycles. In this model the mechanisms of the water vapor molecular diffusion, evaporation/condensation, sorption/desorption of moisture by fibers, Brownian diffusion of the virus, filtration of virus, capillary penetration of the viruses with the liquid water and latent heat generation due to phase change are considered. Meanwhile, the theoretical predictions are compared with experimental data, and good agreement is observed between the two, indicating that the model is satisfactory. Also, the effects of structural and materials properties on virus transfer are investigated.


Joint Statement on Re-introduction of Hospital and Office-Based Procedures for the Practicing Urogynecologist and Gynecologist


title: Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States

text: BACKGROUND: Highly pathogenic avian influenza A (HPAI) viruses found in poultry and wild birds occasionally infect humans and can cause serious disease. In 2014, the Advisory Committee on Immunization Practices (ACIP) reviewed data from one licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use during inter-pandemic periods among persons with occupational exposure. To guide vaccine policy decisions, we conducted a survey of laboratory workers to assess demand for HPAI vaccination. METHODS: We designed an anonymous web survey (EpiInfo 7.0) to collect information on demographics, type of work and time spent with HPAI viruses, and interest in HPAI vaccination. Eligible participants were identified from 42 entities registered with United States Department of Agriculture’s Agricultural Select Agent program in 2016 and emailed electronic surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access were surveyed. Descriptive analysis was performed. RESULTS: Overall, 131 responses were received from 33 principal investigators, 26 research scientists, 24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated response rate was 15% among the laboratory personnel of responding principal investigators. One hundred respondents reported working in a BSL-3E area where HPAI experiments occurred with a mean time of 5.1–11.7 h per week. Overall, 49% were interested in receiving an A(H5N1) vaccine. By role, interest was highest among students (80%) and among those who spent >50% of their time in a BSL-3E area (64%). Most (61%) of those who said they might be or were not interested in vaccine believed it would not provide additional protection to current safety practices. CONCLUSIONS: Half of responding laboratory workers was interested in receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at risk of occupational exposure could be used along with existing safety practices to protect this population.


title: Conformational changes in redox pairs of protein structures

text: Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity.


title: Whole blood cytokine profiles in cats infected by feline coronavirus and healthy non-FCoV infected specific pathogen-free cats

text: In this study, the cytokine profiles of clinically healthy cats naturally infected with feline coronavirus (FCoV), of cats with feline infectious peritonitis (FIP) and of specific pathogen-free (SPF) cats were investigated in whole blood using a traditional reverse-transcriptase polymerase chain reaction (RT-PCR) assay and a semi-quantitative method of analysis based on computerised quantification of positive bands. The low inter-assay coefficient of variation recorded demonstrated that this method is highly repeatable. Compared with SPF cats, cytokine production was upregulated in most of the samples from FCoV-positive non-symptomatic cats. The appearance of a case of FIP in the cattery was associated with an increased expression of cytokines, in particular there was an increased production of IL-1β and IFN-γ, suggesting that these cytokines might protect infected cats from the disease. This hypothesis was also supported by the low levels of IFN-γ recorded in blood from cats with FIP.


title: The interference by maternally-derived antibody with active immunization of farm animals against foot-and-mouth disease

text: Summary Foot-and-mouth disease (FMD) is a highly contagious disease affectingruminants and pigs. In countries in which control of FMD relies predominantly on vaccination, young stock ingest specific anti-FMD virus antibodies in the colostrum. This maternally-derived antibody (MDA) provides immediate protection against infection with FMD virus, but also interferes with the development of active immunity following vaccination. However, susceptibility to infection precedes the ability to respond to vaccination in the presence of MDA. Currently available vaccines cannot overcome this inhibitory effect of MDA, and protection of young stock can only be provided by their- isolation from FMD virus.


title: En route to Peptide Therapeutics for COVID 19: Harnessing Potential Antigenic Mimicry Between Viral and Human Proteins

text: Molecular mimicry is a general strategy used by pathogens to infect the host cells. The emergence of SARS-CoV-2 virus has resulted in more than 6,700,000 infections and 390,000 deaths worldwide. Coronavirus disease (COVID-19) is an infectious disease caused by this virus. In this project concept, we aim to focus on the peptide-protein interaction analysis using two important drug targets in SARS-CoV-2 such as spike (S) protein and nucleocapsid (N) protein. These proteins play an important role in the virus entry and encapsidation of the viral particles. Motifs or functional regions in these two proteins must be sharing sequence homology with human protein (ACE2) which may be involved in the binding mechanism. The results will show a set of motif regions which can disrupt the viral infection. Once we identify these sets of antigenic determinant regions, antibody binding activity studies can be performed by in vitro methods. Our results from this study may suggest the existence of antigenic mimicry between SARS-CoV-2 and host proteins. The hit peptide components will have therapeutic applications to be developed into a wide variety of medicinal formulations against SARS-CoV-2 such as vaccine, intranasal and inhalation formulations. Also, the choice of conserved regions will lead to development of cross protective therapeutics against wide range of coronaviruses.


title: Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach

text: With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.


title: When colds kill

text: Colds are usually just a nuisance but last year a new strain killed at least 140 people. Is the common cold getting nastier?


title: Structural Basis of Evasion of Cellular Adaptive Immunity by HIV-1 Nef

text: The HIV-1 protein Nef inhibits antigen presentation by class I MHC (MHC-I). Here the mechanism of this activity is revealed by the crystal structure of a protein complex consisting of Nef, the MHC-I cytoplasmic domain (MHC-I CD), and the μ1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-μ1 interface encompassing the cargo-recognition site of μ1 and the proline rich strand of Nef. The Nef C-terminus induces a novel conformational change in μ1, while the N-terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on μ1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.


title: COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals

text: Abstract The novel coronavirus 2019, or COVID-19, infection has rapidly spread through the New York metropolitan area since the first reported case in the state on March 1, 2020. New York currently represents an epicenter for COVID-19 infection in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early experience with seven COVID-positive patients in pregnancy, including two women who were diagnosed with COVID-19 following an asymptomatic initial presentation. We now describe a series of 43 test-confirmed cases of COVID-19 presenting to a pair of affiliated New York City hospitals over two weeks from March 13 to 27, 2020. Fourteen (32.6%) patients presented without any COVID-associated viral symptoms, and were identified either after developing symptoms during admission or following the implementation of universal testing for all obstetrical admissions on March 22. Of these, 10/14 (71.4%) developed symptoms or signs of COVID-19 infection over the course of their delivery admission or early after postpartum discharge. Of the other 29 (67.4%) patients who presented with symptomatic COVID-19 infection, three women ultimately required antenatal admission for viral symptoms, and an additional patient represented six days postpartum after a successful labor induction with worsening respiratory status that required oxygen supplementation. There were no confirmed cases of COVID-19 detected in neonates upon initial testing on the first day of life. Applying COVID-19 disease severity characteristics as described by Wu et al, 37 (86%) women possessed mild disease, four (9.3%) exhibited severe disease, and two (4.7%) developed critical disease; these percentages are similar to those described for non-pregnant adults with COVID-19 infections (about 80% mild, 15% severe, and 5% critical disease).


title: Global challenges to urology practice during the COVID‐19 pandemic

text: Since the first report of coronavirus commonly termed as COVID-19 in China, it has progressed into a pandemic and Italy has been one of the countries worst hit. Coronaviruses are enveloped ribonucleic acid (RNA) viruses that cause respiratory, entero-hepatic, and neurologic diseases in humans and mammals. More specifically the coronavirus causing the current pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The common symptoms include a dry continuous cough, fever and shortness of breath; severe cases involve pneumonia which may require ventilatory support.


title: Captive breeding of wildlife resources—China's revised supply‐side approach to conservation

text: The conservation and utilization of wild animals in China often raises public concerns. Thus, the Chinese government is increasingly exploring sustainable development of wildlife resources, and has implemented a series of measures, such as the modification of the Wildlife Protection Law (WPL), implementation of captive breeding licenses, an animal marking system, forest certification, and other actions to regulate captive breeding and utilization of wildlife. At the same time, the government tries to meet the Chinese traditional demand for wildlife products. We first introduce wildlife utilization as an internationally accepted conservation tool, and describe market‐based wildlife farming as a legal substitute for wild‐hunted animals. Second, we highlight the importance of wildlife products in Chinese culture and economy and review some successful examples of wildlife utilization in China, showing that the supply‐side approach is a viable alternative to classical conservation. Subsequently, we outline benefits of, and drawbacks to, China's ‘conservation through utilization’ approach, resulting in the implementation of China's new, revised WPL. We discuss merits and shortcomings of China's revised WPL and respond to recent national and international criticism on China's supply‐side approach to conservation. We strongly propose that captive breeding is a feasible approach to China's wildlife conservation–utilization dilemma, and much work is needed to promote the progress, such as legislation restructure, government attention, duties clarification, and so on. © 2019 The Wildlife Society.


title: Circovirus in Tissues of Dogs with Vasculitis and Hemorrhage

text: We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.


title: The causal relationship between electricity consumption and economic growth in a Gaming and Tourism Center: The case of Macao SAR, the People’s Republic of China

text: Abstract A number of Asian cities decided to establish gaming and resort facilities in order to capitalize on the growing number of gamblers and their family members in Asia. In doing so, they expect to sustain economic growth but, on the other hand, will consume a considerable amount of energy. Nevertheless, the causal relationship between economic growth and electricity consumption in this type of service-oriented territories has never been investigated. Using the historical data obtained from the Government of Macao SAR, we found that electricity consumption and economic growth in terms of gross domestic product are co-integrated for the period of 1999 Quarter 1–2008 Quarter 4. Moreover, vector error correction (VEC) models indicated a lack of short-run relationships but showed that there was a long-run equilibrium relationship between electricity consumption and gross domestic product. The accuracy of VEC models was assessed by using the mean squared error and the mean absolute error. The error analysis shows that VEC models reproduced time series of gross domestic product and electricity consumption in difference form accurately.


title: Rethinking case fatality ratios for covid-19 from a data-driven viewpoint

text: The case fatality ratio (CFR) for COVID-19 is difficult to estimate. One difficulty is due to ignoring or overestimating time delay between reporting and death. We claim that all of these cause large errors and artificial time dependence of the CFR. We find that for each country, there is a unique value of the time lag between reported cases and deaths versus time, that yields the optimal correlation between them is a specific sense. We find that the resulting corrected CFR (deaths shifted back by this time lag, divided by cases) is actually constant over many months, for many countries, but also for the entire world. This optimal time lag and constant CFR for each country can be found through a simple data driven algorithm. The traditional CFR (ignoring time lag) is spuriously time-dependent and its evolution is hard to quantify. Our corrected CFR is constant over time, therefore an important index of the pandemic in each country, and can be inferred from data earlier on, facilitating improved early estimates of COVID-19 mortality.


title: Evaluation of the Efficacy of a Recombinant Adenovirus Expressing the Spike Protein of Porcine Epidemic Diarrhea Virus in Pigs

text: In recent years, many studies have shown that recombinant adenovirus live vector-based vaccines are a promising novel vaccine candidate against virus infection. Therefore, in this study, a new type of recombinant adenovirus expressing the spike (S) protein of porcine epidemic diarrhea virus (PEDV), rAd-PEDV-S, was generated, and its characteristics were determined. Then, its efficacy as a vaccine candidate was evaluated in 4-week-old pigs. The results showed that the S protein could be well expressed at a high level in rAd-PEDV-S-infected cells and that the viral titers could reach 10(11) PFU/mL. Further animal experimental results showed that rAd-PEDV-S elicited a significant PEDV-specific humoral immune response after vaccination (P < 0.05). In addition, rAd-PEDV-S provided partial protection for pigs against the highly virulent PEDV challenge. The results presented in this study indicate that the adenovirus vector can be used as a vaccine delivery vector for the development of a PEDV vaccine and is a promising novel vaccine candidate for future prevention and control of porcine epidemic diarrhea (PED), but its efficacy still needs to be improved in the future.


title: Behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection

text: Abstract Dysfunction of subcortical serotoninergic neurons has been implicated in some behaviour disturbances. The serotoninergic neurons in the dorsal and median raphe project widely in the brain. They innervate the olfactory bulbs and can be targets for exogenous agents attacking the olfactory epithelium and bulbs. We report here an injury to the serotoninergic neurons after intranasal infection in 12-day-old rats with a temperature-sensitive mutant of vesicular stomatitis virus. The brain infection was focal and transient. Viral antigens could no longer be detected 13–15 days after infection. In spite of this the animals, as adults, had a severe serotonin depletion in the cerebral cortex and hippocampus, and showed abnormal locomotor and explorative behaviour as well as learning deficits. The neocortex was histologically intact and parameters related to other neurotransmitters such as dopamine, noradrenaline, GABA and acetylcholine showed no marked changes. A relatively selective damage to serotoninergic nuclei as a result of virus neuroinvasion through a natural portal of entry, may constitute a new pathogenetic mechanism for cortical dysfunction and behavioural deficits.


title: Sub- or supercritical transmissibilities in a finite disease outbreak: Symmetry in outbreak properties of a disease conditioned on extinction

text: Abstract This work is concerned with the transmissibility of a disease, on observation of an outbreak of limited size. When such an outbreak occurs, an accurate estimate of the transmissibility of the responsible pathogen is essential for an appropriate response to future outbreaks. Transmissibility is usually characterised in terms of the reproduction number, R, which is the mean number of new cases of infection produced by a single infectious individual. A subcritical reproduction number (R < 1) guarantees that an outbreak will eventually die out of its own accord. By contrast, a supercritical reproduction number (R > 1) does not guarantee spread of the disease, since even with appreciable transmissibility, an outbreak may become extinct due to stochastic effects associated with a small number of infected individuals. Once the number of infectious individuals is conditioned on extinction, we show that an exact symmetry of the underlying theory ensures two distinct values of R, one larger than unity, the other smaller than unity, for which all outbreak properties are identical, with no signature of difference. Therefore a disease with a subcritical R, or its supercritical counterpart, when conditioned on extinction, have, for a given outbreak, identical individual likelihoods. In the full likelihood, this symmetry is lost, since the individual likelihood for a subcritical R is weighted by an extinction probability of unity, but the individual likelihood of a supercritical R is weighted by a sub-unity extinction probability. However, the inference can still benefit from the underlying symmetry, since it yields a mapping of all supercritical reproduction numbers onto the subcritical domain (R < 1), thereby speeding up evaluation of the likelihood profile. The symmetry holds in the standard situation, where the distribution of secondary cases is Poisson, as well as where this distribution has a negative binomial form and super-spreading can occur.


title: Pharmacists at the frontline beating the COVID-19 pandemic

text: As the lockdowns are being observed all over the globe and the national level pharmacy professionals are performing frontline roles, this editorial highlights the role of pharmacists in the COVID − 19 pandemic. Pharmacists globally are providing services amidst pandemic, including TRIAGE services, seeing patients and reducing the patients’ burden on health care facilities such as hospitals and GP practices. Pharmacists are also working to providing home deliveries, as well as dealing with the increasing number of patients coming through to pharmacies with the other ailments. Pharmacy associations have issued their guidelines and in this editorial, several global examples of pharmacists’ role in the COVID 19 are being discussed. Pakistan is used as a country case study in this editorial. The editorial also elaborates how pharmacists in the UK and Pakistan have teamed up together to compile 10-steps protection guidelines for the pharmacy teams in Pakistan in English and Urdu language. This 10-point guidance educates community pharmacies for safety and standard operation as the number of patients in the country continues to rise. These guidelines are endorsed by the government and private bodies. These can be adopted and adapted by any country; keeping in view their laws and regulations.


title: Short communication: Low risk of transmission of severe acute respiratory syndrome on airplanes: the Singapore experience

text: The risk of transmission of severe acute respiratory syndrome (SARS) on airplanes is of major concern to the public and airline industry. We examined data from flights to Singapore with SARS patients on board in order to assess this risk. In‐flight transmission occurred only in one of the three flights with symptomatic SARS patients on board. The incidence was estimated to be 1 out of 156 passengers. The risk of in‐flight transmission of SARS appears to be far lower than that reported for influenza, but may be increased with superspreaders on board.


title: The ACE2/Angiotensin-(1–7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1–7)

text: The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1–7)/MAS, whose end point is the metabolite ANG-(1–7). ACE2 and other enzymes can form ANG-(1–7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1–7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1–7) in physiology and disease, with particular emphasis on the brain.


title: Infectious Diseases, Urbanization and Climate Change: Challenges in Future China

text: China is one of the largest countries in the world with nearly 20% of the world’s population. There have been significant improvements in economy, education and technology over the last three decades. Due to substantial investments from all levels of government, the public health system in China has been improved since the 2003 severe acute respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major population health issue and this may be exacerbated by rapid urbanization and unprecedented impacts of climate change. This commentary aims to explore China’s current capacity to manage infectious diseases which impair population health. It discusses the existing disease surveillance system and underscores the critical importance of strengthening the system. It also explores how the growing migrant population, dramatic changes in the natural landscape following rapid urbanization, and changing climatic conditions can contribute to the emergence and re-emergence of infectious disease. Continuing research on infectious diseases, urbanization and climate change may inform the country’s capacity to deal with emerging and re-emerging infectious diseases in the future.


title: Scientific Opinion on an update on the present knowledge on the occurrence and control of foodborne viruses

text: A review of the biology, epidemiology, diagnosis and public health importance of foodborne viruses was performed. Data needs to support a risk assessment were also identified. In addition possible control options and their anticipated impact to prevent or reduce the number of foodborne viral human infections were identified, including the scientific reasons for and against the establishment of food safety criteria and process hygiene criteria for viruses for certain food categories. Food may be contaminated by virus during all stages of the food supply chain, and transmission can occur by consumption of food contaminated during the production process (primary production, or during further processing), or contaminated by infected food handlers. Transmission of zoonotic viruses (e.g. HEV) can also occur by consumption of products of animal origin. Viruses do not multiply in foods, but may persist for extended periods of time as infectious particles in the environment, or in foods. At the EU‐level it is unknown how much viral disease can be attributed to foodborne spread. The relative contribution of different sources (shellfish, fresh produce, food handler including asymptomatic shedders, food handling environment) to foodborne illness has not been determined. The Panel recommends focusing controls on preventive measures to avoid viral contamination rather than trying to remove/inactivate these viruses from food. Also, it is recommended to introduce a microbiological criteria for viruses in bivalve molluscs, unless they are labelled “to be cooked before consumption”. The criteria could be used by food business operators to validate their control options. Furthermore, it is recommended to refine the regulatory standards and monitoring approaches in order to improve public health protection. Introduction of virus microbiological criteria for classification of bivalve molluscs production areas should be considered. A virus monitoring programme for compliance with these criteria should be risk based according to the findings of a sanitary survey.


title: A Replication-incompetent Rift Valley Fever Vaccine: Chimeric Virus-like Particles Protect Mice and Rats Against Lethal Challenge

text: Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins G(N) and G(C), nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate.


Antigenic Differentiation of Mouse Hepatitis Viruses by Neutralization Test


title: Does an Upper Respiratory Tract Infection During Pregnancy Affect Perinatal Outcomes? A Literature Review

text: Upper respiratory tract infection (URTI) is a ubiquitous but often benign pathology most commonly of viral etiology. This review focuses on perinatal outcomes following URTI during pregnancy. Few data exist on the explicit topic of URTI and adverse perinatal outcomes. The entire URTI burden among pregnant women is not properly represented by the studies included in this review, because only those infections severe enough to warrant hospitalization have been studied. Most probably, the number of URTIs in pregnant women not requiring hospitalization is far larger, but this has yet to be quantified. Clearly, there are logistical barriers to obtaining such statistics. Severe URTI requiring hospitalization during pregnancy was noted to be associated with adverse perinatal complications. URTI was found to be positively correlated with preterm delivery (PTD; less than 37 weeks gestation), lower birth weight, and cesarean deliveries, without a significant effect on the rates of perinatal mortality or low Apgar scores. There appears to be a possible link between various infectious processes that occur during pregnancy and the outcome of a PTD. The inflammatory environment present during infection includes high levels of cytokines that are known to increase prostaglandins, which, in turn, can induce preterm birth. Further studies should evaluate whether URTI not requiring hospitalization has any effect on perinatal outcomes.


Ethical Considerations of Thoracic Transplant and Circulatory Support during the COVID-19 Pandemic: A Closer Look at Pulmonary Vascular Disease


title: Long noncoding RNAs in innate immunity

text: Long noncoding RNAs (lncRNAs) have been shown to play important roles in immune cell development and immune responses through different mechanisms, such as dosage compensation, imprinting, enhancer function, and transcriptional regulation. Although the functions of most lncRNAs are unclear, some lncRNAs have been found to control transcriptional or post-transcriptional regulation of the innate and adaptive immune responses via new methods of protein–protein interactions or pairing with DNA and RNA. Interestingly, increasing evidence has elucidated the importance of lncRNAs in the interaction between hosts and pathogens. In this review, an overview of the lncRNAs modes of action, as well as the important and diversified roles of lncRNAs in immunity, are provided, and an emerging paradigm of lncRNAs in regulating innate immune responses is highlighted.


title: Evaluation of the Cepheid Respiratory Syncytial Virus and Influenza Virus A/B real-time PCR analyte specific reagent

text: Abstract Two rapid real-time RT-PCR assays, specific for respiratory syncytial virus (RSV) and influenza A and B, were evaluated for the detection of these viruses in clinical respiratory samples. The RSV assay was applied to 100 samples and the Influenza A and B assay applied to 96 samples all of which had been tested previously by an “in-house” multiplex real-time PCR assay. Forty-three samples were negative for RSV by both methods and 56 samples were positive by both methods. One sample was negative by the new RSV assay although it was positive for RSV A by the “in-house” test. Thirty-nine samples were negative for influenza virus by both methods and 55 samples were positive by both assays. Two samples were negative by the new influenza assay however they were positive by the “in-house” influenza assay. The new assays did not cross react with samples containing other viruses including parainfluenza 1, 2, and 4; human metapnuemovirus; coronavirus 229E, NL63, OC43; rhinovirus; adenovirus; bocavirus and had a specificity of 100% and a sensitivity of 98.2% for RSV and 96.5% for influenza respectively. The results of this study demonstrate that the new assays are specific and sensitive for the detection of RSV and influenza viruses in clinical samples.


title: Passive immunisation, an old idea revisited: Basic principles and application to modern animal production systems

text: Abstract Immunisation by administration of antibodies (immunoglobulins) has been known for more than one hundred years as a very efficient means of obtaining immediate, short-lived protection against infection and/or against the disease-causing effects of toxins from microbial pathogens and from other sources. Thus, due to its rapid action, passive immunisation is often used to treat disease caused by infection and/or toxin exposure. However immunoglobulins may also be administered prior to exposure to infection and/or toxin, although they will not provide long-lasting protection as is seen with active immunisation (vaccination) in which an immunological memory is established by controlled exposure of the host to the pathogen in question. With multi-factorial infectious diseases in production animals, especially those that have proven hard to control by vaccination, the potential of passive immunisation remains big. This review highlights a number of examples on the use of passive immunisation for the control of infectious disease in the modern production of a range of animals, including pigs, cattle, sheep, goat, poultry and fish. Special emphasis is given on the enablement of passive immunisation strategies in these production systems through low cost and ease of use as well as on the sources, composition and purity of immunoglobulin preparations used and their benefits as compared to current measures, including vaccination (also comprising maternal vaccination), antibiotics and feed additives such as spray-dried plasma. It is concluded that provided highly efficient, relatively low-price immunoglobulin products are available, passive immunisation has a clear role in the modern animal production sector as a means of controlling infectious diseases, importantly with a very low risk of causing development of bacterial resistance, thus constituting a real and widely applicable alternative to antibiotics.