title: Humoral and Cellular Immune Responses in Turkey Poults Infected with Turkey Coronavirus

text: Abstract The objective of the present study was to elucidate the kinetics of humoral and cellular immune responses of turkey poults infected with turkey coronavirus (TCV). Turkey poults were orally inoculated with TCV at 10 d of age, and the immune responses were analyzed at 1, 3, 7, 14, 21, 28, 42, and 63 d postinfection (PI) in three different experiments. Total Ig to TCV was initially detected at 7 and 14 d PI in Experiments 1 and 3. In addition, Ig gradually increased from 7 to 21 d PI and remained at 80 immunofluroescent antibody assay (IFA) titers or more thereafter. Lymphocyte proliferation responses of spleen cells to concanavalin A were higher in TCV-infected turkeys than in noninfected control turkeys with significant differences (P < 0.05) being noted at 14 and 63 d PI in Experiment 2 and at 3 and 28 d PI in Experiment 3. Strong IFA staining response to TCV antigen was observed in intestines of turkeys at 1, 3, and 7 d PI, and the response declined from 14 to 28 d PI in Experiment 3. In Experiment 3, the IgG isotype antibody response to TCV was markedly increased after 21 d PI and remained high until 63 d PI. The IgM isotype antibody response to TCV was 1.40 and 0.91 at 7 and 14 d PI, respectively. The IgA isotype antibody response to TCV was very low as detected at 7 (0.13), 14 (0.20), and 21 (0.17) d PI. Turkeys infected with TCV had significantly higher (P < 0.05) antibody response to sheep erythrocytes than noninfected controls at 7 d PI. Virus-specific lymphocyte proliferation response of spleen cells was significantly stimulated (P < 0.05) at 63 d PI in Experiment 3. The proportion of the CD4+ subpopulation of T lymphocytes was significantly increased (P < 0.05) at 1, 7, and 21 d PI in Experiment 3. The results indicate that humoral and cellular immunities to TCV are elicited in turkeys following infection with TCV.


title: Clinical, virological and epidemiological characteristics of rhinovirus infections in early childhood: A comparison between non-hospitalised and hospitalised children

text: Abstract Background Several studies have been published regarding the epidemiology and clinical significance of the different rhinovirus (RV) species (-A, -B and -C). However, data on RV types and the associations with clinical outcome in young children are limited. Here, we investigated the clinical, virological and epidemiological characteristics of RV infections in young children with mild or asymptomatic infection (non-hospitalised children) and in symptomatic young children admitted to the hospital. Objectives The aim of this study was to evaluate associations between different characteristics of RV infections and clinical outcome in young children. Study design RV-infected children were retrospectively selected from a Dutch birth cohort (EUROPA-study) and from hospitalised children admitted to the hospital because of respiratory symptoms. In total 120 RV-typed samples could be selected from 65 non-hospitalised and 49 hospitalised children between November 2009 and December 2012. Results RV-A was the predominant species in both study populations, followed closely by RV-C. RV-B was observed only sporadically. The distribution of the RV species was comparable in non-hospitalised and hospitalised children. In children with respiratory distress who required ICU-admission the distribution of RV species did not differ significantly from the non-hospitalised children. No predominant RV type was present in non-hospitalised nor hospitalised children. However, hospitalised children were younger, had more often an underlying illness, a higher RV load and more frequently a bacterial co-infection. Conclusions Clinical outcome of RV infected young children was not related to RV species or types, but may more likely be influenced by multiple (host-specific) factors.


title: Evolution of infectious bronchitis virus in Taiwan: Positively selected sites in the nucleocapsid protein and their effects on RNA-binding activity

text: Abstract RNA recombination has been shown to underlie the sporadic emergence of new variants of coronavirus, including the infectious bronchitis virus (IBV), a highly contagious avian pathogen. We have demonstrated that RNA recombination can give rise to a new viral population, supported by the finding that most isolated Taiwanese (TW) IBVs, similar to Chinese (CH) IBVs, exhibit a genetic rearrangement with the American (US) IBV at the 5’ end of the nucleocapsid (N) gene. Here, we further show that positive selection has occurred at two sites within the putative crossover region of the N-terminal domain (NTD) of the TW IBV N protein. Based on the crystal structure of the NTD, the stereographic positions of both predicted selected sites do not fall close to the RNA-binding groove. Surprisingly, converting either of the two residues to the amino acid present in most CH IBVs resulted in significantly reduced affinity of the N protein for the synthetic RNA repeats of the viral transcriptional regulatory sequence. These results suggest that modulating the amino acid residue at either selected site may alter the conformation of the N protein and affect the viral RNA–N interaction. This study illustrates that the N protein of the current TW IBV variant has been shaped by both RNA recombination and positive selection and that the latter may promote viral survival and fitness, potentially by increasing the RNA-binding capacity of the N protein.


docid: rygittca

title: Reply to Karagoz et al


title: Hazard to man and the environment posed by the use of urban waste compost: a review

text: Abstract This review presents the current state of knowledge on the relationship between the environment and the use of municipal waste compost in terms of health risk assessment. The hazards stem from chemical and microbiological agents whose nature and magnitude depend heavily on the degree of sorting and on the composting methods. Three main routes of exposure can be determined and are quantified in the literature: (i) The ingestion of soil/compost mixtures by children, mostly in cases of pica, can be a threat because of the amount of lead, chromium, cadmium, PCDD F and fecal streptococci that can be absorbed. (ii) Though concern about contamination through the food chain is weak when compost is used in agriculture, some authors anticipate accumulation of pollutants after several years of disposal, which might lead to future hazards. (iii) Exposure is also associated with atmospheric dispersion of compost organic dust that convey microorganisms and toxicants. Data on hazard posed by organic dust from municipal composts to the farmer or the private user is scarce. To date, microorganisms are only measured at composting plants, thus raising the issue of extrapolation to environmental situations. Lung damage and allergies may occur because of organic dust, Gram negative bacteria, actinomycetes and fungi. Further research is needed on the risk related to inhalation of chemical compounds.


title: Severe Acute Respiratory Syndrome Historical, Epidemiologic, and Clinical Features

text: Severe acute respiratory syndrome coronavirus (SARS-CoV), emerged from China and rapidly spread worldwide. Over 8098 people fell ill and 774 died before the epidemic ended in July 2003. Bats are likely an important reservoir for SARS-CoV. SARS-like CoVs have been detected in horseshoe bats and civet cats. The main mode of transmission of SARS-CoV is through inhalation of respiratory droplets. Faeco-oral transmission has been recorded. Strict infection control procedures with respiratory and contact precautions are essential. Fever and respiratory symptoms predominate, and diarrhea is common. Treatment involves supportive care. There are no specific antiviral treatments or vaccines available.


Corrigendum to: “Letter: Neurosurgery and Coronavirus (COVID-19) Epidemic: Doing our Part” by Pesce et al. Neurosurgery, nyaa115, https://doi.org/10.1093/neuros/nyaa115


title: The impact of COVID‐19 on food retail and food service in Canada: Preliminary assessment

text: COVID‐19 has imposed a series of unique challenges on the food retail and food service sectors in Canada. Almost overnight, the roughly 30% of the food dollar that Canadians have been spending on food away from home has shifted to retail.


title: The role of microRNAs in respiratory viral infection: friend or foe?

text: MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host–pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral‐encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright © 2016 John Wiley & Sons, Ltd.


COVID 2019 – ROLE OF FACULTY MEMBERS TO KEEP MENTAL ACTIVENESS OF STUDENTS


title: 2009 H1N1 Influenza: A Twenty-First Century Pandemic With Roots in the Early Twentieth Century

text: Abstract A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 “Spanish flu” virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigen-based rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.


title: Antimicrobial Decision Making for Enteric Diseases of Cattle

text: Diarrhea in neonatal and adult cattle is common and can be caused by several etiologic agents. As diagnostic testing is not always readily available, practitioners must often decide on a course of treatment based on knowledge of the likely pathogen and their own clinical experience. Antimicrobials have long been used to treat diarrhea in adults and neonates; however, there is increased pressure to prevent unnecessary use of antibiotics in food animal species. This article reviews existing data on the use of antibiotics given to cattle with enteric diseases to decide when they are necessary and which antimicrobials should be used.


title: The emerging role of ACE2 in physiology and disease

text: The renin–angiotensin–aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that may add to our understanding have been discovered in recent years. In particular, the human homologue of ACE (ACE2) has added a higher level of complexity to the RAAS. In a short period of time, ACE2 has been cloned, purified, knocked‐out, knocked‐in; inhibitors have been developed; its 3D structure determined; and new functions have been identified. ACE2 is now implicated in cardiovascular and renal (patho)physiology, diabetes, pregnancy, lung disease and, remarkably, ACE2 serves as a receptor for SARS and NL63 coronaviruses. This review covers available information on the genetic, structural and functional properties of ACE2. Its role in a variety of (patho)physiological conditions and therapeutic options of modulation are discussed. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years

text: Abstract Objectives To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. Methods This was a cross-sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. Results HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co-detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV-infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p =0.006), but had more comorbidities (40% and 27%, respectively; p =0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r =−0.636, p <0.001) but no correlation with rainfall (r =−0.036, p =0.866). Conclusion HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co-detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.


title: Medical implication in the Bible and its relevance to modern medicine

text: Abstract The Holy Bible, as the root of Western civilization, has imposed great influence in the fields far beyond religion. In this thesis, the author intended to reveal the medical implication in the Holy Bible and its relevance to the modern medical science by exploring the biblical medical information and comparing it with the current medical theory and practice. The conclusion of the exploration is surprising yet inspiring: the Holy Bible, as an ancient religious book, contains rich medical information around themes such as sexual relations, dietary guidelines, hygiene, etc., which is not at odds, but in harmony with the modern medicine.


title: Godzilla in the corridor: The Ontario SARS crisis in historical perspective

text: Summary Ontario nurses were employed as the front-line workers when SARS descended upon Toronto in March 2003. Once the crisis had subsided, many nurses remarked that SARS had forever altered their chosen profession; employment, which they once viewed as relatively safe, had been transformed into potentially life-threatening. This discussion provides descriptions of these expressions through nurses who experienced the crisis and chose to go on the public record. Secondly, it compares the subjective perceptions of those nurses to those held by nurses who worked through historical epidemics of unknown or contested epidemiology. The historical literature on nursing in yellow fever, cholera and influenza epidemics has been employed to offer insight. The goal is to determine whether the SARS outbreak was a unique experience for nurses or whether similar experiences were shared by nurses in the past? In summary, the reactions of nurses when confronted with the possibility of contracting a deadly disease remain altogether human, not dissimilar in past or present. Nurses’ responses to SARS can be usefully studied within a larger historical vision of crisis nursing, and information or impressions from earlier crises are potentially of interest to the nursing profession.


title: Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain

text: The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.


title: COVID-19 When Leadership Calls

text: Abstract From the minute our organization received our first presumptive positive COVID-19 patient, and throughout our journey, many challenges and obstacles have been presented for health care leadership. Priorities are rapidly shifting, anxiety and fear are present, and knowing where to focus support is a challenge. As I sit and reflect on lessons learned throughout this experience, I can't help but continue to focus on frontline leadership and their important role in this entire process.


title: SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain

text: Virus genome sequence variants that appear over the course of an outbreak can be exploited to map the trajectory of the virus from one susceptible host to another. While such variants are usually of no functional significance, in some cases they may allow the virus to transmit faster, change disease severity, or confer resistance to antiviral therapies. Since the discovery of SARS-CoV-2 as the cause of COVID-19, the virus has spread around the globe, and thousands of SARS-CoV-2 genomes have been sequenced. The rate of sequence variation among SARS-CoV-2 isolates is modest for an RNA virus but the enormous number of human-to-human transmission events has provided abundant opportunity for selection of sequence variants. Among these, the SARS-CoV-2 Spike protein variant, D614G, was not present in the presumptive common ancestor of this zoonotic virus but was first detected in late January in Germany and China. The D614G variant steadily increased in frequency and now constitutes >97% of isolates world-wide, raising the question whether D614G confers a replication advantage to SARS-CoV-2. Structural models predict that D614G would disrupt contacts between the S1 and S2 domains of the Spike protein and cause significant shifts in conformation. Using single-cycle vectors we showed that D614G is three to nine-fold more infectious than the ancestral form on human lung and colon cell lines, as well as on other human cell lines rendered permissive by ectopic expression of human ACE2 and TMPRSS2, or by ACE2 orthologues from pangolin, pig, dog, or cat. Nonetheless, monoclonal antibodies targeting the receptor binding domain of the SARS-CoV-2 Spike protein retain full neutralization potency. These results suggest that D614G was selected for increased human-to-human transmission, that it contributed to the rapidity of SARS-CoV-2 spread around the world, and that it does not confer resistance to antiviral therapies targeting the receptor binding domain.


title: Novel Dynamic Structures of 2019-nCoV with Nonlocal Operator via Powerful Computational Technique

text: In this study, we investigate the infection system of the novel coronavirus (2019-nCoV) with a nonlocal operator defined in the Caputo sense. With the help of the fractional natural decomposition method (FNDM), which is based on the Adomian decomposition and natural transform methods, numerical results were obtained to better understand the dynamical structures of the physical behavior of 2019-nCoV. Such behaviors observe the general properties of the mathematical model of 2019-nCoV. This mathematical model is composed of data reported from the city of Wuhan, China.


title: Evaluation of the performance of DiaSorin molecular Pneumocystis jirovecii-CMV multiplex real-time PCR assay from bronchoalveolar lavage samples

text: Abstract The aim of this study was to evaluate the performance of the DiaSorin Molecular PJ-CMV multiplex real-time PCR (PJ-CMV PCR) assay (DiaSorin Molecular LLC, USA) in bronchoalveolar lavage (BAL) samples compared to direct immunofluorescence assay (IFA) for the detection of Pneumocystis jirovecii and assess CMV and P. jirovecii co-infection rate in immunosuppressed patients with suspected pneumonia. A total of 125 BAL samples from immunosuppressed patients submitted for PJP-IFA were tested. Surplus samples were saved and further tested by using the PJ-CMV PCR assay. Among the 125 samples, P. jirovecii was detected in 31.2% (39/125) and in 40% (50/125) of the specimens using IFA and PJ-CMV PCR respectively. Eleven of the PJ-CMV PCR positive samples were negative by direct IFA for P. jirovecii. All samples positive by direct IFA were also positive by PJ-CMV PCR. Using the direct IFA as a gold standard, the PJ-CMV PCR sensitivity, specificity, positive predictive value and negative predictive value for detection of P. jirovecii were 100%, 87.2%, 78% and 100%, respectively. However, after reviewing the clinical diagnosis, the specificity and PPV increased to 100%. Of the 50 P. jirovecii samples positive by PJ-CMV PCR, 18 (36%) were also positive for CMV by the PJ-CMV PCR. The co-infection rate was found to be 37.5% (6/16) and 35.2% (12/34) in HIV infected and non-HIV infected patients. This study indicated that the DiaSorin Molecular PJ-CMV multiplex real-time PCR assay has higher sensitivity than direct IFA for detection of P. jirovecii and provides rapid detection of PJ and CMV infection in BAL samples.


title: Direct RNA sequencing and early evolution of SARS-CoV-2

text: Fundamental aspects of SARS-CoV-2 biology remain to be described, having the potential to provide insight to the response effort for this high-priority pathogen. Here we describe the first native RNA sequence of SARS-CoV-2, detailing the coronaviral transcriptome and epitranscriptome, and share these data publicly. A data-driven inference of viral genetic features and evolutionary rate is also made. The rapid sharing of sequence information throughout the SARS-CoV-2 pandemic represents an inflection point for public health and genomic epidemiology, providing early insights into the biology and evolution of this emerging pathogen.


title: Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19

text: Abstract Corona virus disease 2019 (COVID-19) pandemic caused 18 440 deaths world wide as of 25 March 2020 and posing a serious threat to public health. There is a need, therefore, for effective therapeutic strategies to cure this disease. However, high attrition rates, substantial costs and slow pace are the major limitations of novel drug discovery. Drug repurposing, by employing ‘old’ drugs to treat ‘new’ diseases is an attractive approach in drug discovery. Niclosamide (NIC) is an approved anti-helminthic drug with diverse antiviral mechanisms. In this work we hypothesize, the potential antiviral mechanisms of NIC against COVID-19.


title: Community Under Stress: Trust, Reciprocity, and Community Collective Efficacy During SARS Outbreak

text: The study of epidemics is almost non-existent in sociological literature, even though such outbreaks can have detrimental effects on communities. The occurrence of SARS (Severe Acute Respiratory Syndrome) in 2003 provides a rare opportunity to understand the social functioning of a community during the outbreak of an epidemic. To evaluate the extensive social impact of such an outbreak, we focus on the effects of perceived collective efficacy. Specifically, we focus on how the collective efficacy of a community, measured by trust and reciprocal relations, is related to collective action in places where SARS occurred and those where SARS did not occur. The study is based on a unique data set, the 2003 Taiwan Social Image Survey, collected during the outbreak of SARS in Taiwan. Our findings show that community collective efficacy, measured by trust and reciprocity, is not associated with community collective action when an outbreak of an epidemic occurs.


title: Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

text: Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.


title: Epidemiological and ecological modelling reveal diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study

text: Respiratory tract infections (RTI) are responsible for over 4 million deaths per year worldwide with pathobiont carriage a required precursor to infection. Through a cross-sectional community-based nasal self-swabbing study we sought to determine carriage epidemiology for respiratory pathogens amongst bacteria (Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa and Neisseria meningitidis) and viruses (RSV, Influenza viruses A and B, Rhinovirus/Enterovirus, Coronavirus, Parainfluenza viruses 1-3 and Adenovirus (ADV)). Carriage of bacterial and viral species was shown to vary with participant age, recent RTI and the presence of other species. The spatial structure of microbial respiratory communities was less nested (more disordered) in the young (0-4 years) and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2 = 20.42, p = 0.002), indicating spatial clumping of species consistent with facilitative relationships amongst them. Deviations from a neutral model of ecological niches were observed for samples collected in the summer and from older individuals (those aged 5-17, 18-64 and ≥65 years) but not in samples collected from winter, younger individuals (those aged 0-4 years), individuals with recent RTI and individuals without recent RTI, demonstrating the importance of both neutral and niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to sets of respiratory tract samples has yielded novel insights into the factors that drive microbial community composition, such as seasonality and age, as well as species patterns and interactions within the nose.


title: Disseminated Conidiobolus incongruus in a dog: A case report and literature review

text: Conidiobolomycosis is a rare fungal disease of both humans and animals, occurring mainly in tropical and subtropical climates. We describe a disseminated fungal infection in a young, apparently immunocompetent dog who initially presented for antibiotic resistant pneumonia. Histopathology and mycology identified a Conidiobolus sp., further confirmed as Conidiobolus incongruus through DNA sequencing of D1/D2 regions. This is the first report of this species causing disease in dogs and the fifth reported infection in animals.


title: Epidemiology, pathological aspects and genome heterogeneity of feline morbillivirus in Italy

text: Abstract Feline morbillivirus (FeMV) is an emerging morbillivirus first described in cats less than a decade ago. FeMV has been associated with chronic kidney disease of cats characterized by tubulointerstitial nephritis (TIN), although this aspect is still controversial and not demonstrated with certainty. To investigate FeMV prevalence and genomic characteristics, an epidemiological survey was conducted in a total number of 127 household cats originating from two Italian regions, Abruzzi and Emilia-Romagna. A total number of 69 cats originating from three feline colonies were also enrolled for the study. Correlation with TIN was investigated by employing a total number of 35 carcasses. Prevalence of FeMV RNA was higher in urine samples collected from cats of colonies (P = 31.8%, CI 95% 22.1–43.6) compared to household cats (P = 8.66%, CI 95% 4.9–14.9) and in young and middle-aged cats while prevalence of FeMV Abs was higher in old cats. Sequences obtained straight from infected biological samples, either partial or complete, cluster into two clades within FeMV genotype 1, distantly related to FeMV genotype 2. Immunohistochemistry analysis of kidney sections of FeMV RNA positive cats revealed immunoreactivity within epithelial cells of renal tubuli and inflammatory cells. However, statistically significant association between FeMV and renal damages, including TIN, was not demonstrated (p= 0.0695, Fisher exact test). By virus histochemistry performed with FeMV-negative feline tissues and a FeMV isolate, tropism for different cellular types such as inflammatory cells residing in blood vessels of kidney and brain, airway epithelial cells, alveolar macrophages and to a lesser extent, the central nervous system, was demonstrated. Additional studies are warranted in order to establish viral tropism and immune response during the early phases of infection and to disentangle the role of FeMV in co-infection processes.


title: Preparing intensive care for the next pandemic influenza

text: Few viruses have shaped the course of human history more than influenza viruses. A century since the 1918–1919 Spanish influenza pandemic—the largest and deadliest influenza pandemic in recorded history—we have learned much about pandemic influenza and the origins of antigenic drift among influenza A viruses. Despite this knowledge, we remain largely underprepared for when the next major pandemic occurs. While emergency departments are likely to care for the first cases of pandemic influenza, intensive care units (ICUs) will certainly see the sickest and will likely have the most complex issues regarding resource allocation. Intensivists must therefore be prepared for the next pandemic influenza virus. Preparation requires multiple steps, including careful surveillance for new pandemics, a scalable response system to respond to surge capacity, vaccine production mechanisms, coordinated communication strategies, and stream-lined research plans for timely initiation during a pandemic. Conservative models of a large-scale influenza pandemic predict more than 170% utilization of ICU-level resources. When faced with pandemic influenza, ICUs must have a strategy for resource allocation as strain increases on the system. There are several current threats, including avian influenza A(H5N1) and A(H7N9) viruses. As humans continue to live in closer proximity to each other, travel more extensively, and interact with greater numbers of birds and livestock, the risk of emergence of the next pandemic influenza virus mounts. Now is the time to prepare and coordinate local, national, and global efforts.


title: Suspected Case of COVID-19 Associated Pancreatitis in a Child

text: The world has been challenged by SARS CoV-2, a new virus causing pneumonia and acute respiratory distress syndrome, with common symptoms of COVID-19 in pediatric patients including both respiratory and GI symptoms. There is a lack of literature implicating COVID-19 in pancreatitis, yet viruses are generally understood to be a cause of pancreatitis in children. We present a case of a previously well 7-year-old girl, who presented to the Emergency Department with a chief complaint of abdominal pain and anorexia. She was diagnosed with acute pancreatitis with an abnormal lipase, ultrasound and computed tomography, and was found to be COVID-19 positive by polymerase chain reaction. Our case suggests that, in the current pandemic, consideration for SARS CoV-2 testing in children with gastrointestinal symptoms and pancreatitis may be considered. Additionally, this case highlights the need for appropriate personal protective equipment for providers, even when COVID is not initially on the differential


title: The severe acute respiratory syndrome coronavirus 3a is a novel structural protein

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is one of the opening reading frames in the viral genome with no homologue in other known coronaviruses. Expression of the 3a protein has been demonstrated during both in vitro and in vivo infection. Here we present biochemical data to show that 3a is a novel coronavirus structural protein. 3a was detected in virions purified from SARS-CoV infected Vero E6 cells although two truncated products were present predominantly instead of the full-length protein. In Vero E6 cells transiently transfected with a cDNA construct for expressing 3a, a similar cleavage was observed. Furthermore, co-expression of 3a, membrane and envelope proteins using the baculovirus system showed that both full-length and truncated 3a can be assembled into virus-like particles. This is the first report that demonstrated the incorporation of 3a into virion and showed that the SARS-CoV encodes a novel coronavirus structural protein.


La psychiatrie française confrontée à l’inédit : la crise de la COVID-19


title: Similar virus spectra and seasonality in paediatric patients with acute respiratory disease, Ghana and Germany

text: Abstract Epidemiological differences between tropical and temperate regions regarding viruses causing acute respiratory infection are poorly understood. This is in part because methodological differences limit the comparability of data from these two regions. Using identical molecular detection methods, we tested 1174 Ghanaian and 539 German children with acute respiratory infections sampled over 12 months for the 15 most common respiratory viruses by PCR. A total 43.2% of the Ghanaian and 56.6% of the German children tested positive for at least one respiratory virus. The pneumoviruses respiratory syncytial virus and human metapneumovirus were most frequently detected, in 13.1% and 25.1% within the Ghanaian and German children, respectively. At both study sites, pneumoviruses were more often observed at younger ages (p <0.001). In the Ghanaian rainy season, enveloped viruses were detected twice as often as non-enveloped viruses (prevalence rate ratio (PR) 2.0, 95% CI 1.7–2.4). In contrast, non-enveloped viruses were more frequent during the Ghanaian dry season (PR 0.6, 95% CI 0.4–0.8). In Germany, enveloped viruses were also more frequently detected during the relatively colder winter season (PR 1.6, 95% CI 1.2–2.1) and non-enveloped viruses during summer (PR 0.7, 95% CI 0.5–0.9). Despite a distance of about 5000 km and a difference of 44° latitude separating Germany and Ghana, virus spectra, age associations and seasonal fluctuation showed similarities between sites. Neither respiratory viruses overall, nor environmentally stable (non-enveloped) viruses in particular were more frequent in tropical Ghana. The standardization of our sampling and laboratory testing revealed similarities in acute respiratory infection virus patterns in tropical and temperate climates.


title: Quantification of recombinant core-like particles of bluetongue virus using immunosorbent electron microscopy

text: Abstract Immunosorbent electron microscopy was used to quantify recombinant baculovirus-generated bluetongue virus (BTV) core-like particles (CLP) in either purified preparations or lysates of recombinant baculovirus-infected cells. The capture antibody was an anti-BTV VP7 monoclonal antibody. The CLP concentration in purified preparations was determined to be 6.6×1015 particles/l. CLP concentration in lysates of recombinant baculovirus-infected cells was determined at various times post-infection and shown to reach a value of 3×1015 particles/l of culture medium at 96 h post-infection. The results indicated that immunosorbent electron microscopy, aided by an improved particle counting method, is a simple, rapid and accurate technique for the quantification of virus and virus-like particles produced in large scale in vitro systems.


title: Highlights of the 30th International Conference on Antiviral Research

text: Abstract The 30th International Conference on Antiviral Research (ICAR) was held in Atlanta, GA, USA from May 18 to 21, 2017. This report provides an account of award lectures, invited keynote addresses and oral presentations during the meeting. The 2017 Gertrude Elion Memorial Lecture Award by Michael Sofia highlighted one of the most important accomplishments in recent drug discovery in antiviral research, the identification of the hepatitis C virus direct-acting antiviral sofosbuvir and new alternatives to combat hepatitis B virus (HBV) infection. The Antonín Holý Lecture Award by David Chu on medicinal chemistry provided an overview of early developments of nucleoside analogs for the treatment of HIV and varicella zoster virus infection and how this knowledge serves to develop new drugs targeting HBV. Priscilla Yang gave the first ISAR Women in Science lecture. She reported on pharmacological validation of new antiviral targets for dengue, Zika and other flaviviruses. The William Prusoff Young Investigator Lecture Award by Maaike Everts described the Alabama Drug Discovery Alliance and the Antiviral Drug Discovery and Development Consortium, and how they are helping to accelerate the development of new antivirals. The 30th ICAR was a success in promoting new discoveries in antiviral drug development and research. The 31st ICAR will be held in Porto, Portugal, June 11–15, 2018.


title: The Fine Balance: Adapting Clinical Research into COVID‐19 Response

text: Quality clinical research remains a high priority during the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) coronavirus disease (COVID‐19) pandemic response, however, the logistical barriers of conducting research across institutions with differing departmental policy responses and varying resources is a documented problem.


title: Iron Transport Tocopheryl Polyethylene Glycol Succinate in Animal Health and Diseases

text: Gut health is the starting place for maintaining the overall health of an animal. Strategies to maintain gut health are, thus, an important part in achieving the goal of improving animal health. A new strategy to do this involves two molecules: the iron transport protein ovotransferrin (IT) and α-tocopheryl polyethylene glycol succinate (TPGS), which result in the novel formulation of ITPGS. These molecules help reduce gut pathogens, while enhancing the absorption and bioavailability of therapeutic drugs, phytomedicines, and nanomedicines. This, in turn, helps to maintain normal health in animals. Maintaining the gastrointestinal tract (GIT) in its normal condition is key for successful absorption and efficacy of any nutrient. A compromised GIT, due to an imbalance (dysbiosis) in the GIT microbiome, can lead to an impaired GI barrier system with impaired absorption and overall health of the animal. The molecules in ITPGS may address the issue of poor absorption by keeping the GI system healthy by maintaining the normal microbiome and improving the absorption of nutrients through multiple mechanisms involving antioxidative, anti-inflammatory, immunomodulatory, and antimicrobial activities. The ITPGS technology can allow the dose of active pharmaceutical or herbal medicine to be significantly reduced in order to attain equal or better efficacy. With complimentary actions between IT and TPGS, ITPGS presents a novel approach to increase the bioavailability of drugs, phytoconstituents, nutrients, and nanomedicines by enhanced transport to the tissues at the site of action, while reducing gut pathogen load. The ITPGS approach appears to be a novel strategy for maintaining the health of animals by manipulation of microbiota.


title: Application of CareDose 4D combined with Karl 3D technology in the low dose computed tomography for the follow-up of COVID-19

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the new coronavirus. Previous studies have shown that the chest CT examination plays an important role in the diagnosis and monitoring of COVID-19. However, some patients with COVID-19 had low white blood cell counts and reduced lymphocyte ratios. Multiple CT examinations may cause radiation damages as well as increase the apoptosis of peripheral blood lymphocytes. A new low-dose CT method should be developed because the regular CT may aggravate the disease. METHOD: Sixty cases were randomly divided into the study group (n = 30) and control group (n = 30). The lung window was reconstructed by Karl 3D iterative technique in the study group. The image quality was subjectively evaluated by two senior chest group diagnostic physicians using a 5-point double-blind method. The value of CT measurement and its standard deviation (SD) was used as an objective evaluation criteria. The volume of CT dose index (CTDI(vol)), dose length product (DLP) and effective dose (ED) from the two groups were compared and analyzed statistically. RESULT: There was no significant difference in the occurrence rates of ground glass opacities, consolidation, crazy-paving pattern, fiber cable shadow and axial interstitial thickening between the study group and control group (p > 0.05). In addition, no significant difference was found for the subjective score of overall image quality and image noise level (SD) between the two groups (p > 0.05). However, significant differences was found in CTDI(vol), DLP, and ED between the study group and the control group (p < 0.05). The effective dose of the study group was reduced by 76% compared to the control group. CONCLUSION: CareDose 4D low-dose scanning combined with Karl 3D iterative reconstruction technology can not only greatly reduce the radiation dose, but also provide images that meet the diagnostic criteria of COVID-19, which can be used as a routine method for the follow-up of COVID-19 patients.


title: Chapter 15 Innate Humoral Defense Factors

text: Abstract Although innate immunity came into the research spotlight in the late 1990s when its instructive role in the adaptive immune response was recognized, innate humoral defense factors have a much older history. The exocrine secretions of the body contain a plethora of distinct soluble factors (lysozyme, lactoferrin, peroxidases, proline-rich proteins, histatins, etc.) that protect the body from mucosal microbial pathogens. More recent studies have established that the humoral arm of innate immunity contains a heterogeneous group of pattern-recognition molecules (e.g., pentraxins, collectins, and ficolins), which perform diverse host-defense functions, such as agglutination and neutralization, opsonization, control of inflammation, and complement activation and regulation. These pattern-recognition molecules, which act as functional predecessors of antibodies (“ante-antibodies”), and the classic soluble innate defense factors form an integrated system with complementary specificity, action, and tissue distribution, and they are the subject of this chapter.


title: Factors Affecting the Disaster Response Competency of Emergency Medical Technicians in South Korea

text: Abstract Purpose This study explored the factors influencing disaster response competency, that is, demographic and disaster-related characteristics, personal disaster (household and workplace) preparedness, disaster risk perception, and self-efficacy in handling disasters among emergency medical technicians in South Korea. Methods The study follows a descriptive, cross-sectional design and uses a self-reported questionnaire. Emergency medical technicians, amounting to 1,020 in all, currently working in firefighting organizations from four South Korean cities (Busan, Daegu, Daejeon, and Ulsan) participated in the study. Results Disaster risk perception, self-efficacy for disaster, participation experience in disaster education/training, and personal disaster (household and workplace) preparedness predicted the disaster response competency of emergency medical technicians in South Korea. Conclusion There is a need for an antidisaster program to enhance the disaster risk perception, self-efficacy, personal disaster (household and workplace) preparedness, and the disaster education/training participation rate toward enhancing disaster response competency of emergency medical technicians in South Korea.


title: Hydrogen Europe paper on the hydrogen sector after Covid-19

text: The Hydrogen Europe industry association has published a paper analysing the hydrogen sector post-Covid-19, which outlines the need for and rationale behind rapid action as a result of the impact of the Covid-19 pandemic.


COVID-19, Aging and Mental Health: Lessons from the First Six Months


title: Development of an RT-PCR diagnostic test for an avian astrovirus

text: Abstract Astroviruses are small round viruses that cause enteric disease in the young of several species. Detection and diagnosis of astrovirus infection in non-human hosts relies heavily on electron microscopy and fluorescent antibody tests. Recently, our laboratory isolated and sequenced an avian astrovirus from poult enteritis mortality syndrome affected turkeys. These studies describe the development of RT-PCR methods, which specifically detect regions of the viral capsid and polymerase genes, and demonstrate their use in detecting astrovirus infection in commercial turkey flocks.


title: Sulfated polymannuroguluronate TGC161 ameliorates leukopenia by inhibiting CD4(+) T cell apoptosis

text: Polysaccharides have aroused considerable interest due to their diverse biological activities and low toxicity. In this study, we evaluated the effect of marine polysaccharide sulfated polymannuroguluronate (TGC161) on the leukopenia induced by chemotherapy. It is found that TGC161 ameliorates the leukopenia. Besides, TGC161 would promote CD4(+) T cell differentiation and maturation in the thymus, but does not have a significant effect on precursor cells in bone marrow. Furthermore, TGC161 inhibits CD4(+) T cell apoptosis in vitro. Collectively, our findings offer a natural and harmless polysaccharide to ameliorate leukopenia.


title: Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding

text: Proteins with RNA chaperone activity are ubiquitous proteins that play important roles in cellular mechanisms. They prevent RNA from misfolding by loosening misfolded structures without ATP consumption. RNA chaperone activity is studied in vitro and in vivo using oligonucleotide- or ribozyme-based assays. Due to their functional as well as structural diversity, a common chaperoning mechanism or universal motif has not yet been identified. A growing database of proteins with RNA chaperone activity has been established based on evaluation of chaperone activity via the described assays. Although the exact mechanism is not yet understood, it is more and more believed that disordered regions within proteins play an important role. This possible mechanism and which proteins were found to possess RNA chaperone activity are discussed here.


title: A case of Listeria monocytogenes meningitis complicated by Hydrocephalus and Intraventricular hemorrhage: A review of treatment options and outcomes

text: Listeria monocytogenes is a gram-positive bacillus known to cause various human infections including central nervous system infections. The most common central nervous system manifestations are meningitis and rhomboencephalitis, however rare complications including hydrocephalus and intracerebral hemorrhage can occur and are associated with increased mortality and incidence of lasting neurologic sequelae. The mortality ranges from 17 % to greater than 30 % in patients with neurological involvement [[1], [2], [3]]. Various case reports have studied the differing treatment approaches and outcomes of patients who experienced these complications, and there is still no consensus on optimal treatment approaches. In this paper, we report a case of Listeria meningitis complicated by both acute hydrocephalus and intracerebral hemorrhage and analyze the factors that led to a favorable outcome by reviewing the existing literature.


title: Halitunal, an unusual diterpene aldehyde from the marine alga Halimeda tuna

text: Abstract Halituna( 1 ), a novel diterpene aldehyde possessing a unique cyclopentadieno[c]pyran ring system, has been isolated from the marine alga Halimeda tuna. The structure of 1 was elucidated by spectroscopic techniques. Halitunal shows antiviral activity against murine coronavirus A59 in-vitro.


title: Suitability of canine herpesvirus as a vector for oral bait vaccination of foxes

text: Abstract Studies were conducted to evaluate the feasibility of using canine herpesvirus (CHV) as a vaccine vector for bait-delivered oral vaccination of wild foxes. To test the viability of CHV in baits, CHV was freeze-dried, incorporated into different baits, stored, and the remaining viral infectivity tested in cell culture after varying periods of time at different storage temperatures. Experimental baits (mouse carcasses) and commercial baits (FOXOFF and PROBAIT) were prepared with either liquid or freeze-dried CHV and tested in two fox trials for their capacity to induce CHV-specific antibodies following oral baiting. Freeze-drying and storage temperatures below 0°C had a stabilizing effect to virus infectivity. When stored at −20°C, freeze-dried CHV retained its full infectivity for up to 3 months in PROBAIT baits, the remaining infectivity in FOXOFF baits was 100-fold less. Oral baiting with CHV induced antiviral serum antibodies in all vaccinated foxes (20/20). None of the vaccinated foxes became ill or shed infectious virus into the environment although viral DNA was detected in body secretions as evaluated by PCR. The results indicate that CHV can be freeze-dried and stored over extended periods of time without loosing much of its infectivity. This is the first report of CHV being used for oral bait vaccination of foxes. It appears that CHV is well suited for use as a recombinant vector for wild canids.


title: Identification of pyrvinium pamoate as an anti-tuberculosis agent in vitro and in vivo by SOSA approach amongst known drugs

text: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant M. tb has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including M. tb H37Rv, Mycobacterium smegmatis, Bacille Calmette-Guérin (BCG), M. tb H37Ra, and drug-resistant M. tb clinical isolates in vitro from 1280 known drugs library. The MIC(99) of PP, the minimum inhibitory concentration that inhibits more than 99% of M. tb H37Rv and the drug-resistant M. tb clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in M. tb H37Rv, multidrug-resistant (MDR) M. tb and extensively drug-resistant (XDR) M.tb-infected mice. Our results clearly show that the PP has the potential application for treatment of TB.


title: Benzotriazole: An overview on its versatile biological behavior

text: Discovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities as well as less adverse effects are reported for triazole derivatives. Consequently, it is not surprising that benzimidazole/benzotriazole derivatives have been found to be biologically active. Since benzimidazole has been widely investigated, this review is focused on defining the place of benzotriazole derivatives in biomedical research, highlighting their versatile biological properties, the mode of action and Structure Activity Relationship (SAR) studies for a variety of antimicrobial, antiparasitic, and even antitumor, choleretic, cholesterol-lowering agents.


docid: hgfvassa

title: COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity—including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others—must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.


title: Crystal structure, vibrational and optic properties of 2-N-methylamino-3-methylpyridine N-oxide – Its X-ray and spectroscopic studies as well as DFT quantum chemical calculations

text: Abstract The crystal and molecular structure and physicochemical properties of 2-N-methylamino-3-methylpyridine N-oxide (MA3MPO) have been studied. MA3MPO was synthesized from 2-amino-3-methylpyridine by several steps to form colorless crystals suitable for crystallographic analysis. The data reveal that MA3MPO crystallizes in the monoclinic space group P21/n. The studied compound contains a nearly flat triply substituted pyridine skeleton whose structure is stabilized by an intramolecular N–H⋅⋅⋅O hydrogen bond. The N-oxide molecules are connected together by weak C–H⋯O hydrogen bonds, an acceptor of which is the oxygen atom from the N-oxide group. This leads to creation of two-dimensional network of hydrogen bonds. Its IR, Raman, UV–Vis and luminescence spectra have been measured and analyzed on the basis of DFT and NBO quantum chemical calculations in which the B3LYP/6-311++G(d,p) approach was applied. The distribution of the electron levels in the studied compound has been analyzed in terms of the possibility of its participation in the ligand-to-lanthanide ion energy transfer.


title: Headaches and the N95 face‐mask amongst healthcare providers

text: Background: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face‐mask. Methods: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face‐mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications). Results: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21–58) participated. Of the 79 (37.3%) respondents who reported face‐mask‐associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1–4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre‐existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03–3.77)] and continuous use of the N95 face‐mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99–3.43)] were associated with development of headaches. Conclusions: Healthcare providers may develop headaches following the use of the N95 face‐mask. Shorter duration of face‐mask wear may reduce the frequency and severity of these headaches.


Lung Surfactant for Pulmonary Barrier Restoration in Patients With COVID-19 Pneumonia


title: Tandem leader proteases of Grapevine leafroll-associated virus-2: Host-specific functions in the infection cycle

text: Abstract Several viruses in the genus Closterovirus including Grapevine leafroll-associated virus-2 (GLRaV-2), encode a tandem of papain-like leader proteases (L1 and L2) whose functional profiles remained largely uncharacterized. We generated a series of the full-length, reporter-tagged, clones of GLRaV-2 and demonstrated that they are systemically infectious upon agroinfection of an experimental host plant Nicotiana benthamiana. These clones and corresponding minireplicon derivatives were used to address L1 and L2 functions in GLRaV-2 infection cycle. It was found that the deletion of genome region encoding the entire L1–L2 tandem resulted in a ~100-fold reduction in minireplicon RNA accumulation. Five-fold reduction in RNA level was observed upon deletion of L1 coding region. In contrast, deletion of L2 coding region did not affect RNA accumulation. It was also found that the autocatalytic cleavage by L2 but not by L1 is essential for genome replication. Analysis of the corresponding mutants in the context of N. benthamiana infection launched by the full-length GLRaV-2 clone revealed that L1 or its coding region is essential for virus ability to establish infection, while L2 plays an accessory role in the viral systemic transport. Strikingly, when tagged minireplicon variants were used for the leaf agroinfiltration of the GLRaV-2 natural host, Vitis vinifera, deletion of either L1 or L2 resulted in a dramatic reduction of minireplicon ability to establish infection attesting to a host-specific requirement for tandem proteases in the virus infection cycle.


Letter to the Editor on “An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)”, Back to Basics


title: Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype

text: The outbreak of the coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, spread worldwide after its emergence in China. Whether rich or poor, all nations are struggling to cope with this new global health crisis. The speed of the threat’s emergence and the quick response required from public health authorities and the public itself makes evident the need for a major reform in pandemic surveillance and notification systems. The development and implementation of a graded, individual-level pandemic notification system could be an effective tool to combat future threats of epidemics. This paper describes a prototype model of such a notification system and its potential advantages and challenges for implementation. Similar to other emergency alerts, this system would include a number of threat levels (level 1-5) with a higher level indicating increasing severity and intensity of safety measures (eg, level 1: general hygiene, level 2: enhanced hygiene, level 3: physical distancing, level 4: shelter in place, and level 5: lockdown). The notifications would be transmitted to cellular devices via text message (for lower threat levels) or push notification (for higher threat levels). The notification system would allow the public to be informed about the threat level in real time and act accordingly in an organized manner. New Zealand and the United Kingdom have recently launched similar alert systems designed to coordinate the ongoing COVID-19 pandemic response more efficiently. Implementing such a system, however, faces multiple challenges. Extensive preparation and coordination among all levels of government and relevant sectors are required. Additionally, such systems may be effective primarily in countries where there exists at least moderate trust in government. Advance and ongoing public education about the nature of the system and its steps would be an essential part of the system, such that all members of the public understand the meaning of each step in advance, similar to what has been established in systems for other emergency responses. This educational component is of utmost importance to minimize adverse public reaction and unintended consequences. The use of mass media and local communities could be considered where mobile phone penetration is low. The implementation of such a notification system would be more challenging in developing countries for several reasons, including inadequate technology, limited use of data plans, high population density, poverty, mistrust in government, and tendency to ignore or failure to understand the warning messages. Despite the challenges, an individual-level pandemic notification system could provide added benefits by giving an additional route for notification that would be complementary to existing platforms.


Risk Perceptions and Behaviour: Towards Pandemic Control of Emerging Infectious Diseases: International Research on Risk Perception in the Control of Emerging Infectious Diseases


docid: edctpsjf

title: ECHOCARDIOGRAPHY DURING PRONE POSITION MECHANICAL VENTILATION IN COVID-19 PATIENTS: A PROPOSAL FOR A NEW APPROACH


title: The Role of the Adeno-Associated Virus Capsid in Gene Transfer

text: Adeno-associated virus (AAV) is one of the most promising viral gene transfer vectors that has been shown to effect long-term gene expression and disease correction with low toxicity in animal models, and is well tolerated in human clinical trials. The surface of the AAV capsid is an essential component that is involved in cell binding, internalization, and trafficking within the targeted cell. Prior to developing a gene therapy strategy that utilizes AAV, the serotype should be carefully considered since each capsid exhibits a unique tissue tropism and transduction efficiency. Several approaches have been undertaken in an effort to target AAV vectors to specific cell types, including utilizing natural serotypes that target a desired cellular receptor, producing pseudotyped vectors, and engineering chimeric and mosaic AAV capsids. These capsid modifications are being incorporated into vector production and purification methods that provide for the ability to scale-up the manufacturing process to support human clinical trials. Protocols for small-scale and large-scale production of AAV, as well as assays to characterize the final vector product, are presented here. The structures of AAV2, AAV4, and AAV5 have been solved by X-ray crystallography or cryo-electron microscopy (cryo-EM), and provide a basis for rational vector design in developing customized capsids for specific targeting of AAV vectors. The capsid of AAV has been shown to be remarkably stable, which is a desirable characteristic for a gene therapy vector; however, recently it has been shown that the AAV serotypes exhibit differential susceptibility to proteases. The capsid fragmentation pattern when exposed to various proteases, as well as the susceptibility of the serotypes to a series of proteases, provides a unique fingerprint for each serotype that can be used for capsid identity validation. In addition to serotype identification, protease susceptibility can also be utilized to study dynamic structural changes that must occur for the AAV capsid to perform its various functions during the virus life cycle. The use of proteases for structural studies in solution complements the crystal structural studies of the virus. A generic protocol based on proteolysis for AAV serotype identification is provided here.


title: Epidemiology of respiratory viral infections in children enrolled in a study of influenza vaccine effectiveness

text: BACKGROUND: Influenza-like illness (ILI) confers a high annual morbidity in young children. We report the epidemiology of ILIs in children who participated in an influenza vaccine effectiveness study during the 2010 Southern Hemisphere influenza season in Sydney, Australia. METHODS: Children aged 0·5–3 years were prospectively recruited from child care centres (CCCs). We classified them as fully vaccinated, partially vaccinated and unvaccinated according to their receipt of unadjuvanted vaccines containing influenza A (H1N1)pdm09. For 13 weeks commencing 30 July 2010, parents reported when their children developed an ILI (fever ≥37·8°C/feverishness plus ≥1 respiratory symptom) and collected nose and/or throat swabs for multiplex respiratory virus polymerase chain reaction (PCR) testing. Health impacts were assessed by telephone interview at enrolment and two weeks after each ILI. RESULTS: There were 124 ILIs reported in 105 of 381 enrolled children. Swabs were taken in 117 ILIs: 175 viruses were identified from 103 swabs. Adeno- and rhinoviruses were most frequently identified; 44% of swabs yielded multiple viruses. No virus was associated with more severe symptoms, although rhinovirus-related ILIs lasted longer. Nose swabs had a higher virus detection rate than throat swabs. Influenza-vaccinated children were 1·6 times (P = 0·001) more likely than unvaccinated children to have a non-influenza ILI. CONCLUSION: Adeno- and rhinoviruses were the most common viruses causing ILI. Swabs taken by parents are an effective method for sample collection. Influenza-like illness was more common in children vaccinated against influenza in this observational study, but prior health-seeking behaviour may have contributed to this difference.


title: Extension of the known distribution of a novel clade C betacoronavirus in a wildlife host

text: Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green(®) real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.


title: Peroral immunotheraphy with yolk antibodies for the prevention and treatment of enteric infections

text: Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are very good producers of specific antibodies. After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified. A laying hen produces more than 20 g of yolk antibodies (IgY) per year. These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent bacterial and viral infections.


title: Twenty Years of Active Bacterial Core Surveillance

text: Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.


Re: Ming-Chun Chan, Sharon E.K. Yeo, Yew-Lam Chong, Yee-Mun Lee. Stepping Forward: Urologists’ Efforts During the COVID-19 Outbreak in Singapore. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2020.03.004


title: Sequence analysis of a reovirus isolated from the winter moth Operophtera brumata (Lepidoptera: Geometridae) and its parasitoid wasp Phobocampe tempestiva (Hymenoptera: Ichneumonidae)

text: Abstract A reovirus was isolated from Operophtera brumata (ObRV) and its parasitoid wasp Phobocampe tempestiva. Each of the 10 dsRNA genome segments of ObRV was sequenced and shown to contain a single open reading frame (ORF). Conserved motifs ([+ve] 5′-AAATAAA … G/TAGGTT-3′) were found at the termini of each segment, with the exception of Seg-6 and Seg-8, where the 5′ termini were 5′-AACAAA…-3′. The putative proteins encoded by each segment were compared with those of other members of the family Reoviridae. Phylogenetic comparisons to published sequences for the RNA-dependent RNA polymerase genes from other reoviruses indicated that ObRV is most closely related to members of the genus Cypovirus. However, unlike the cypoviruses, ObRV has a double-layered capsid structure. When the protein encoded by ObRV Seg-10 was expressed (by inserting the open reading frame into a baculovirus expression vector) no ‘occlusion bodies’ were observed in the recombinant baculovirus infected insect cell cultures. This suggests that unlike the cypoviruses, Seg-10 of ObRV does not contain a polyhedrin gene. Further phylogenetic comparisons also identified relationships between Seg-2 and Seg-10 of ObRV, and genes of Diadromus pulchellus Idnoreovirus 1 (DpIRV1), suggesting that ObRV represents a new species from the genus Idnoreovirus.


title: Facing the Next Pandemic: Ready or Not

text: Abstract Influenza pandemics generally occur at 30-40 year intervals and it has been nearly 40 years since the last one. A global pandemic will result in devastating social, economical, and health consequences. Preparedness is crucial to minimize the threat to hematopoietic stem cell transplant (HSCT) patients. Vaccines, antivirals, and infection control measures are important elements of prevention. Antivirals, often given presumptively, are the mainstay of therapy.


title: Crimean-Congo haemorrhagic fever in travellers: A systematic review

text: Summary Background The recent Ebola epidemic has increased public awareness of the risk of travel associated viral haemorrhagic fever (VHF). International preparedness to manage imported cases Ebola virus infection was inadequate, highlighted by cases of nosocomial transmission. Crimean-Congo haemorrhagic fever (CCHF) is a re-emerging tick-borne VHF centred in the Eurasian region, affecting a large geographical area and with human-to-human transmission reported, especially in the healthcare setting. Objectives To systematically review the characteristics of travel associated Crimean-Congo haemorrhagic fever. Methods A systematic review of travel-associated cases of CCHF was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. PubMed, SCOPUS, Science Citation Index (SCI) and ProMED databases were searched for reports published between January 1960 and January 2016. Three independent reviewers selected and reviewed studies and extracted data. Results 21 cases of travel associated CCHF were identified, of which 12 died (3 outcome unknown) and 4 secondary (nosocomial) infections were reported. Risk occupations or activities for CCHF infection were reported in 8/12 cases when data were available. Travel from Asia to Asia occurred in 9 cases, Africa to Africa occurred in 5 cases, Africa to Europe in 3 cases, Asia to Europe in 2 cases and Europe to Europe in 2 cases. Conclusion CCHF related to travel is rare, is generally associated with at risk activities/occupation and is frequently fatal. Key to early diagnosis and prevention of nosocomial transmission is an understanding of CCHF risk factors and the geographical distribution of CCHF. International travel to CCHF endemic areas is increasing and clinicians and laboratory personnel managing returning travellers should maintain a high index of suspicion.


title: COVID‐19: A global transplant perspective on successfully navigating a pandemic

text: The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health‐care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.


title: Construction of Simple and Efficient siRNA Validation Systems for Screening and Identification of Effective RNAi-Targeted Sequences from Mammalian Genes

text: RNA interference (RNAi) is an evolutionarily conserved mechanism of gene silencing induced by double-stranded RNAs (dsRNAs). Among the widely used dsRNAs, small interfering RNAs (siRNAs) and short hairpin RNAs have evolved as extremely powerful and the most popular gene silencing reagents. The key challenge to achieving efficient gene silencing especially for the purpose of therapeutics is mainly dependent on the effectiveness and specificity of the selected RNAi-targeted sequences. Practically, only a small number of dsRNAs are capable of inducing highly effective and sequence-specific gene silencing via RNAi mechanism. In addition, the efficiency of gene silencing induced by dsRNAs can only be experimentally examined based on inhibition of the target gene expression. Therefore, it is essential to develop a fully robust and comparative validation system for measuring the efficacy of designed dsRNAs. In this chapter, we focus our discussion on a reliable and quantitative reporter-based siRNA validation system that has been previously established in our laboratory. The system consists of a short synthetic DNA fragment containing an RNAi-targeted sequence of interest and two expression vectors for targeting reporter and triggering siRNA expressions. The efficiency of siRNAs is determined by their abilities to inhibit expression of the targeting reporters with easily quantified readouts including enhanced green fluorescence protein and firefly luciferase. Since only a readily available short synthetic DNA fragment is needed for constructing this reliable and efficient reporter-based siRNA validation system, this system not only provides a powerful strategy for screening highly effective RNAi-targeted sequences from mammalian genes but also implicates the use of RNAi-based dsRNA reagents for reverse functional genomics and molecular therapeutics.


title: Impacts of rapid flu clinic services at an emergency department during the pandemic flu season

text: BACKGROUND: We performed an assessment of an independent rapid flu clinic service (RFCS) unit, which was set up outside the emergency department (ED) during the 2009 H1N1 pandemic season. The unit was able to relieve the crowding of regular ambulatory and emergency services. METHODS: Between August and December 2009, a total of 6,152 patients with influenza-like illness were enrolled in this observational retrospective study. Patients with positive influenza tests were interviewed to evaluate the efficiency of RFCS. RESULTS: The mean length of stay (LOS) for the RFCS was 50 minutes, which was shorter than the LOS for ambulatory services (1 hour) and regular ED services (3.5 hours). Overall, 88% of patients were satisfied with the RFCS. Of 6,152 patients receiving flu tests, 1,235 (20%) had a positive result. Fever (odds ratio [OR], 4.28, 95% confidence interval [CI]: 3.11-5.89), fever combined with cough and sore throat (OR, 2.52; 95% CI: 2.18-2.92), fever combined with sore throat (OR, 2.42; 95% CI: 2.13-2.75), history of contacting confirmed flu patients within 7 days (OR, 2.40; 95% CI: 2.07-2.78), fever combined with cough (OR, 2.19; 95% CI: 1.92-2.47), sore throat (OR, 2.03, 95% CI: 1.79-2.30); and cough (OR, 1.91, 95% CI: 1.69-2.17) were significantly associated with positive influenza tests. CONCLUSION: Setting up the RFSC was beneficial to health care facilities during a pandemic flu season.


title: Childhood community-acquired pneumonia: A review of etiology- and antimicrobial treatment studies

text: Abstract Community acquired pneumonia (CAP) is a leading cause of childhood morbidity worldwide. Because of the rising antimicrobial resistance rates and adverse effects of childhood antibiotic use on the developing microbiome, rational prescribing of antibiotics for CAP is important. This review summarizes and critically reflects on the available evidence for the epidemiology, etiology and antimicrobial management of childhood CAP. Larger prospective studies on antimicrobial management derive mostly from low- or middle-income countries as they have the highest burden of CAP. Optimal antimicrobial management depends on the etiology, age, local vaccination policies and resistance patterns. As long as non-rapid surrogate markers are used to distinguish viral- from bacterial pneumonia, the management is probably suboptimal. For a young child with signs of non-severe pneumonia (with or without wheezing), watchful waiting is recommended because of probable viral etiology. For children with more severe CAP with fever, a five-day oral amoxicillin course would be the first choice therapy and dosage will depend on local resistance rates. There is no clear evidence yet for superiority of a macrolide-based regimen for all ages. For cases with CAP requiring hospitalization, several studies have shown that narrow-spectrum IV beta-lactam therapy is as effective as a broad-spectrum cephalosporin therapy. For most severe disease, broad-spectrum therapy with or without a macrolide is suggested. In case of empyema, rapid IV-to-oral switch seems to be equivalent to prolonged IV treatment.


COVID-19 precautions and recommendations


title: Determining training and education needs pertaining to highly infectious disease preparedness and response: A gap analysis survey of US emergency medical services practitioners

text: BACKGROUND: The Ebola virus disease outbreak highlighted the lack of consistent guidelines and training for workers outside of hospital settings. Specifically, emergency medical services (EMS) workers, who are frequently the first professionals to evaluate patients, often do not have advanced notice of patient diagnosis, and have limited time in their national curricula devoted to highly infectious disease (HID) identification and containment. All of these can place them at increased risk. To explore the depth of US EMS practitioners' HID training and education, a pilot gap analysis survey was distributed to determine where the aforementioned can be bolstered to increase occupational safety. METHODS: Electronic surveys were distributed to EMS organization members. The survey collected respondent willingness to encounter HID scenarios; current policies and procedures; and levels of knowledge, training, and available resources to address HIDs. RESULTS: A total of 2,165 surveys were initiated and collected. Eighty percent of frontline personnel were aware that their agency had an HID standard operating guideline. Almost 85% of respondents correctly marked routes of exposure for select HIDs. More than half of respondents indicated no maximum shift times in personal protective equipment. DISCUSSION: This research suggests EMS practitioners could benefit from enhanced industry-specific education, training, and planning on HID mitigation and management. CONCLUSION: Strengthening EMS preparedness in response to suspected or confirmed HID cases may not only improve patient outcomes, but also worker and community safety.


title: Development of loop-mediated isothermal amplification assay for detection of human coronavirus-NL63

text: Abstract Human coronavirus NL63 was identified in 2004 in the Netherlands. Due to the high prevalence and world-wide distribution of this pathogen, it is essential to develop a sensitive and specific detection assay suitable for use in a routine diagnostic laboratory. Techniques based on PCR or real-time PCR are laborious and expensive. Detailed analysis of the HCoV-NL63 genome permitted the identification of a conserved nucleic acid sequential motif, which was sufficient for the design of a loop-mediated isothermal amplification (LAMP) assay. Evaluation of the method showed that the test is specific to HCoV-NL63 and that it does not cross-react with other respiratory viruses. The detection limit was found to be 1 copy of RNA template per reaction in cell culture supernatants and clinical specimens.


title: COVID-19 and social distancing

text: AIM: COVID-19 has spread rapidly worldwide since it began, greatly affecting peoples' lives, social economies and medical systems. At present, little is known about the disease, and vaccines are still under development. Therefore, in the face of severe outbreaks, previous effective experience can help people better protect themselves and their families. The aim of this article is to discuss the social distancing measures for COVID-19. SUBJECTS AND METHODS: Literature and document search. RESULTS: Recent research and a novel coronavirus pneumonia prediction model revealed social distancing measures and wearing masks are required to mitigate hospital system overload and prevent pathogen exposure. After a series of social distancing measures, there are 309 cities with zero cases and 34 cities with confirmed cases in China as of April 13, 2020. CONCLUSION: From China's experience with novel coronavirus pneumonia, we know that social distancing is the most effective measure at present. We need to win more time to allow limited medical resources to save lives.


title: Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains

text: Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.


title: Effect of a quadrivalent vaccine against respiratory virus on the incidence of respiratory disease in weaned beef calves

text: Abstract We investigated the effect of vaccination of male beef calves (mean age±S.D.: 158±31days) against bovine herpes virus (BHV-1 or IBR virus), bovine respiratory syncitial virus (BRSV), bovine viral diarrhea (BVD) virus and para-influenza (PI3) virus on the incidence of respiratory disease during the first forty days after weaning and entering a feed-lot in Portugal. In May 2003, Mertolenga, Preta and mixed-breed calves from 10 different beef herds, were systematically assigned (by order of entrance in a chute) to two treatment groups, before moving to a common feed-lot. One hundred and twenty five male calves were vaccinated with a quadrivalent vaccine (Rispoval 4®) and revaccinated after 21–27 days while 148 herdmates were injected with saline (0.9% NaCl) on the same occasions. The incidence and severity of clinical cases of “bovine respiratory disease” (BRD) were evaluated every day during the first 40 days after entering the feed-lot. Morbidity (3% vs. 14%) and mortality (0% vs. 4%) due to BRD were significantly lower in the vaccinated group. Ten days after revaccination, the calves were treated with an antimicrobial – ending the study – after an outbreak of BRD caused a high incidence of disease in the non-vaccinated group. In conclusion, our results showed that Rispoval 4®, a quadrivalent vaccine against respiratory viruses, under field conditions, reduces morbidity and mortality due to BRD in beef calves after weaning.


title: Utilizing Technology to Enhance Screening for Highly Infectious Diseases

text: • Digital survey applications can be used to create highly infectious disease screening tools; • Digital screening tools simplify patient screening for non-clinical staff at facility entrances; • Digital screening tools can be monitored remotely to assist with compliance. Quick identification and isolation of patients with highly infectious diseases is extremely important in healthcare settings today. This study focused on the creation of a digital screening tool using a free and publicly available digital survey application to screen patients during a measles outbreak in New York City. The results indicate that digital tools are an effective alternative to paper tools due to their ease of use and remote compliance monitoring capabilities.


title: Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes

text: The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17-producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes.


docid: napicnni

title: Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

text: BACKGROUND: In the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking. METHODS: We isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler’s murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages. RESULTS: We have identified and validated new microglial- and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection. CONCLUSIONS: The differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1545-x) contains supplementary material, which is available to authorized users.


title: Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement

text: BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.


title: Treatment of Severe Pneumonia due to COVID-19 with Peginterferon alfa 2a

text: The outbreak of the new coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Until now, no definite effective treatment has been identified. We reported 3 patients with severe COVID-19 treated with pegylated interferon alfa 2a with satisfactory recovery. Based on these observations, randomized studies with interferons should be considered in deteriorating patients infected with COVID-19.