title: High-Throughput SNP Genotyping: Combining Tag SNPs and Molecular Beacons

text: In the last decade, molecular beacons have emerged to become a widely used tool in the multiplex typing of single nucleotide polymorphisms (SNPs). Improvements in detection technologies in instrumentation and chemistries to label these probes have made it possible to use up to six spectrally distinguishable probes per reaction well. With the remarkable advances made in the characterization of human genome diversity, it has been possible to describe empirical patterns of SNPs and haplotype variation in the genome of diverse human populations. These patterns have revealed that the human genome is structured in blocks of strong linkage disequilibrium (LD). Because SNPs tend to be in LD with each other, common haplotypes share common SNPs and thus the majority of the diversity in a region can be characterized by typing a very small number of SNPs; so-called tag SNPs. Herein lies the advantage of the multiplexing ability of molecular beacons, since it becomes possible to use as few as 30 probes to interrogate several haplotypes in a high-throughput approach. Thus, through the combined use of tag SNPs and molecular beacons it becomes possible to type individuals for clinically relevant haplotypes in a high-throughput manner at a cost that is orders of magnitude less than that for high throughput sequencing methods.


title: Hydrologic, land cover, and seasonal patterns of waterborne pathogens in Great Lakes tributaries

text: Abstract Great Lakes tributaries are known to deliver waterborne pathogens from a host of sources. To examine the hydrologic, land cover, and seasonal patterns of waterborne pathogens (i.e. protozoa (2), pathogenic bacteria (4) human viruses, (8) and bovine viruses (8)) eight rivers were monitored in the Great Lakes Basin over 29 months from February 2011 to June 2013. Sampling locations represented a wide variety of land cover classes from urban to agriculture to forest. A custom automated pathogen sampler was deployed at eight sampling locations which provided unattended, flow-weighted, large-volume (120–1630 L) sampling. Human and bovine viruses and pathogenic bacteria were detected by real-time qPCR in 16%, 14%, and 1.4% of 290 samples collected while protozoa were never detected. The most frequently detected pathogens were: bovine polyomavirus (11%), and human adenovirus C, D, F (9%). Human and bovine viruses were present in 16.9% and 14.8% of runoff-event samples (n = 189) resulting from precipitation and snowmelt, and 13.9% and 12.9% of low-flow samples (n = 101), respectively, indicating multiple delivery mechanisms could be influential. Data indicated human and bovine virus prevalence was different depending on land cover within the watershed. Occurrence, concentration, and flux of human viruses were greatest in samples from the three sampling locations with greater than 25% urban influence than those with less than 25% urban influence. Similarly, occurrence, concentration, and flux of bovine viruses were greatest in samples from the two sampling locations with greater than 50 cattle/km2 than those with less than 50 cattle/km2. In seasonal analysis, human and bovine viruses occurred more frequently in spring and winter seasons than during the fall and summer. Concentration, occurrence, and flux in the context of hydrologic condition, seasonality, and land use must be considered for each watershed individually to develop effective watershed management strategies for pathogen reduction.


title: Transcriptional Regulation of Antiviral Interferon-Stimulated Genes

text: Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect.


title: The risk factors associated with MERS-CoV patient fatality: A global survey

text: Abstract Risk factors associated with Middle East respiratory syndrome coronavirus (MERS-CoV) infection outcome were established by analyses of WHO data from September 23, 2012 to 18 June 2018. Of the 2220 reported cases, 1408 cases, including 451 MERS-CoV deaths, were analyzed. The case fatality rate was 32% (95% CI: 29.4–34.5). Compared to MERS patients ≤30 years old, those with >30 years had the adjusted odds ratio estimate for death of 2.38 [95% CI: 1.75–3.22]. This index was 1.43 [95% CI: 1.06–1.92] for Saudi patients in comparison to non-Saudi; 1.76 [95% CI: 1.39–2.22] for patient with comorbidity in comparison to those without comorbidity; 0.58 [95% CI: 0.44–0.75] for those who had close contact to a camel in the past 14 days and 0.42 [95% CI: 0.31–0.57] for patients with >14 days with onset of signs and hospital admission compared to patients with ≤14 days.


title: A one step quantitative RT-PCR for detection of SARS coronavirus with an internal control for PCR inhibitors

text: Abstract In this study, we report a one step quantitative RT-PCR assay for severe acute respiratory syndrome (SARS) diagnosis. The overall detection rate for clinical samples collected from Days 1 to 9 of disease onset is 86.2% and the specificity of the assay is 100%. To detect false negative results due to PCR inhibitors or faulty RNA extraction, we have further modified this one step RT-PCR assay for simultaneous detection of severe acute respiratory syndrome (SARS) coronavirus (CoV) and 18S ribosomal RNA (rRNA) as an internal positive control.


title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea

text: In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.


title: Prevalence of acute liver injury and hypertransaminemia in patients with COVID-19: a protocol for a systematic review

text: INTRODUCTION: COVID-19 has spread rapidly in China and around the world. Published studies have revealed that some patients with COVID-19 had abnormal liver function in laboratory tests. However, the results were inconsistent and the analysis of epidemiological data stratified by the severity of COVID-19 was not available in previous meta-analyses. Furthermore, these meta-analyses were suspected of overestimating the incidence of liver injury in patients with COVID-19 because some studies considered transaminase elevation as liver injury, which might partially result from cardiac and muscle injury. This systematic review aims to enrol published literatures related to COVID-19 without language restriction, analyse the data based on the severity of the COVID-19 and explore the impact of varied definitions of liver injury on the incidence of liver injury. METHODS AND ANALYSIS: We have conducted a preliminary search on PubMed and Excerpta Medica Database on 13 April 2020, for the studies published after December 2019 on the prevalence of acute liver injury and hypertransaminemia in patients with COVID-19. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will estimate the pooled incidence of hypertransaminemia and acute liver injury in patients with COVID-19 by using the random-effects model. The I(²) test will be used to identify the extent of heterogeneity. Publication bias will be assessed by funnel plot and performing the Begg’s and Egger’s test if adequate studies are available. We will perform a risk of bias assessment using the Joanna Briggs Institute’s critical appraisal checklist. ETHICS AND DISSEMINATION: Since this study will be based on the published data, it does not require ethical approval. The final results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020179462.


title: Rapid Antigen Tests for Diagnosis of Pandemic (Swine) Influenza A/H1N1

text: We found that the sensitivities of 3 rapid influenza antigen tests for pandemic influenza A/H1N1 virus were low to moderate: BD Directigen EZ Flu A+B test (Becton Dickinson), 46.7%; BinaxNOW Influenza A&B (Inverness Medical), 38.3%; and QuickVue Influenza A+B Test (Quidel), 53.3%. A patient with influenza-like illness who has a negative rapid antigen test result should undergo further testing using reverse-transcription polymerase chain reaction.


title: Epidemiología de COVID-19 en México: del 27 febrero al 30 de abril de 2020

text: Resumen Antecedentes. El primer caso de COVID-19 se detectó en México el 27 de febrero de 2020. El 30 de abril, 64 días después de este primer diagnóstico, el número de pacientes aumentó exponencialmente, alcanzando un total de 19.224 casos confirmados y 1.859 (9,67%) fallecidos. En respuesta a este brote global, resumimos el estado actual del conocimiento sobre COVID-19 en México. Métodos. Los datos se obtuvieron del sitio web oficial del Ministerio de Salud en México. El período analizado fue entre el 27 de febrero y el 30 de abril de 2020. Los casos se confirmaron mediante RT-PCR en tiempo real y se analizaron los datos epidemiológicos, demográficos y clínicos. Resultados. La mayoría de los casos de COVID-19 se ubicaron en la Ciudad de México. La edad promedio de los pacientes fue de 46 años. De los 12.656 casos confirmados, el mayor número de infectados ocurre en el rango de edad entre 30 y 59 años (65,85%), y hubo una mayor incidencia en hombres (58,18%) que en mujeres (41,82%). Los pacientes fallecidos tenían una o múltiples comorbilidades, principalmente hipertensión (45,53%), diabetes (39,39%) y obesidad (30,4%). En los primeros 64 días de epidemia, China había reportado 80.304 casos con una tasa de mortalidad del 3,66%. Conclusiones. Nuestros resultados indican la transmisión temprana de COVID-19 en México. La epidemiología descriptiva muestra las similitudes entre los casos de COVID-19 de México y China. En el mismo período de la curva epidémica, observamos en México una reducción en el número de casos confirmados de COVID-19 y una mayor tasa de mortalidad en comparación con China. Abstract Background The first case of COVID-19 detected in Mexico was on the 27th of February 2020. On the 30th of April, 64 days after this first diagnosis, the number of patients had increased exponentially, reaching 19,224 confirmed cases and 1859 (9.67%) deaths. In response to this global outbreak, we summarise the current state of our understanding regarding COVID-19 in Mexico. Methods. We obtained the data from the official website of the Ministry of Health in Mexico. The study period was between the 27th of February and the 30th of April 2020. The cases were confirmed using real-time reverse transcription-polymerase chain reaction, and we analysed epidemiological, demographic and clinical data. Results. In Mexico, most cases of COVID-19 were located in Mexico City. The mean age of the patients was 46 years. Of the 12,656 confirmed cases, most infected individuals were between the ages of 30 and 59 years (65.85%), and there was a higher incidence rate in men (58.18%) than in women (41.82%). The patients who died had one or more comorbidities, mainly hypertension (45.53%), diabetes (39.39%) and obesity (30.4%). In the first 64 days of the epidemic, China had reported 80,304 cases with a mortality rate of 3.66%. Conclusions. Our results indicate an early transmission of COVID-19 in Mexico. The descriptive epidemiology shows similarities between the cases of COVID-19 in Mexico and those in China. In the same period of the epidemic curve, we observed a reduction in the number of confirmed cases of COVID-19 in Mexico and a higher mortality rate compared with that of China.


title: Effectiveness of hand hygiene and provision of information in preventing influenza cases requiring hospitalization

text: Abstract Background The objective of the study was to investigate the effectiveness of non-pharmacological interventions in preventing cases of influenza requiring hospitalization. Methods We performed a multicenter case-control study in 36 hospitals, in 2010 in Spain. Hospitalized influenza cases confirmed by reverse-transcription polymerase chain reaction and three matched controls (two hospital and one community control) per case were selected. The use of non-pharmacological measures seven days before the onset of symptoms (frequency of hand washing, use of alcohol-based hand sanitizers and handwashing after touching contaminated surfaces) was collected. Results We studied 813 cases hospitalized for influenza and 2274 controls. The frequency of hand washing 5-10 times (adjusted odds ratio [aOR]=0.65) and >10 times (aOR=0.59) and handwashing after contact with contaminated surfaces (aOR=0.65) were protective factors and were dose-responsive (p<0.001). Alcohol-based hand sanitizers were associated with marginal benefits (aOR=0.82). Conclusions Frequent handwashing should be recommended to prevent influenza cases requiring hospitalization.


title: Evaluation of Viruses Associated With Acute Respiratory Infections in Long-Term Care Facilities Using a Novel Method: Wisconsin, 2016‒2019

text: Abstract Residents of long-term care facilities (LCTFs) have high morbidity and mortality associated with acute respiratory infections (ARIs). Limited information exists on the virology of ARI in LTCFs, where virological testing is reactive. We report on findings of a surveillance feasibility substudy from a larger prospective trial of introducing rapid influenza diagnostic testing (RIDT) at 10 Wisconsin LTCFs. Any resident with symptoms consistent with ARI had a nasal swab specimen collected for RIDT by staff. Following RIDT, the residual swab was placed into viral transport medium and tested for influenza using Reverse transcription polymerase chain reaction, and for 20 pathogens using a multiplex polymerase chain reaction respiratory pathogen panel. Numbers of viruses in each of 7 categories (influenza A, influenza B, coronaviruses, human metapneumovirus, parainfluenza, respiratory syncytial virus, and rhinovirus/enterovirus) across the 3 years were compared using χ2. Totals of 160, 215, and 122 specimens were collected during 2016‒2017, 2017‒2018, and 2018‒2019, respectively. Respiratory pathogen panel identified viruses in 54.8% of tested specimens. Influenza A (19.2%), influenza B (12.6%), respiratory syncytial virus (15.9%), and human metapneumovirus (20.9%) accounted for 69% of all detections, whereas coronaviruses (17.2%), rhinovirus/enterovirus (10.5%) and parainfluenza (3.8%) were less common. The distribution of viruses varied significantly across the 3 years (χ2 = 71.663; df = 12; P < .001). Surveillance in LTCFs using nasal swabs collected for RIDT is highly feasible and yields high virus identification rates. Significant differences in virus composition occurred across the 3 study years. Simple approaches to surveillance may provide a more comprehensive assessment of respiratory viruses in LTCF settings.


title: Structural alteration of tight and adherens junctions in villous and crypt epithelium of the small and large intestine of conventional nursing piglets infected with porcine epidemic diarrhea virus

text: Abstract Integrity of the intestinal epithelium is critical for proper functioning of the barrier that regulates absorption of water and restricts uptake of luminal bacteria. It is maintained mainly by tight junctions (TJs) and adherens junctions (AJs). We conducted immunofluorescence (IF) staining for in situ identification of zonula occludin (ZO)-1 proteins for TJ and E-Cadherin proteins for AJ in the small and large intestinal villous and crypt epithelium of nursing pigs infected with porcine epidemic diarrhea virus (PEDV). Twenty 9-day-old piglets [PEDV-infected (n =9) and Mock (n =11)] from PEDV seronegative sows, were orally inoculated [8.9log10 genomic equivalents/pig] with PEDV PC21A strain or mock. At post-inoculation days (PIDs) 1–5, infected pigs showed severe watery diarrhea and/or vomiting and severe atrophic enteritis. By immunohistochemistry, PEDV antigens were evident in enterocytes lining the villous epithelium. At PIDs 1–5, PEDV-infected pigs exhibited mildly to extensively disorganized, irregular distribution and reduced expression of ZO-1 or E-Cadherin in villous, but not crypt epithelial cells of the jejunum and ileum, but not in the large intestine, when compared to the negative controls. The structural destruction and disorganization of TJ and AJ were extensive in PEDV-infected pigs at PIDs 1–3, but then appeared to reversibly recover at PID 5, as evident by increased numbers of ZO-1-positive epithelial cells and markedly improved appearance of E-Cadherin-positive villous epithelium. Our results suggest a possible involvement of structurally impaired TJ and AJ in the pathogenesis of PEDV, potentially leading to secondary bacterial infections.


title: Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune(®) vaccine

text: In order to assess the immunotherapeutic potential on canine visceral leishmaniasis of the Leishmune(®) vaccine, formulated with an increased adjuvant concentration (1 mg of saponin rather than 0.5 mg), 24 mongrel dogs were infected with Leishmania (L.) chagasi. The enriched-Leishmune(®) vaccine was injected on month 6, 7 and 8 after infection, when animals were seropositive and symptomatic. The control group were injected with a saline solution. Leishmune(®)-treated dogs showed significantly higher levels of anti-FML IgG antibodies (ANOVA; p < 0.0001), a higher and stable IgG2 and a decreasing IgG1 response, pointing to a TH1 T cell mediated response. The vaccine had the following effects: it led to more positive delayed type hypersensitivity reactions against Leishmania lysate in vaccinated dogs (75%) than in controls (50%), to a decreased average of CD4+ Leishmania-specific lymphocytes in saline controls (32.13%) that fell outside the 95% confidence interval of the vaccinees (41.62%, CI95% 43.93–49.80) and an increased average of the clinical scores from the saline controls (17.83) that falls outside the 95% confidence interval for the Leishmune(®) immunotherapy-treated dogs (15.75, CI95% 13.97–17.53). All dogs that received the vaccine were clustered, and showed lower clinical scores and normal CD4+ counts, whereas 42% of the untreated dogs showed very diminished CD4+ and higher clinical score. The increase in clinical signs of the saline treated group was correlated with an increase in anti-FML antibodies (p < 0.0001), the parasitological evidence (p = 0.038) and a decrease in Leishmania-specific CD4+ lymphocyte proportions (p = 0.035). These results confirm the immunotherapeutic potential of the enriched-Leishmune(®) vaccine. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog's potential infectiosity to phlebotomines. The enriched-Leishmune(®) vaccine was subjected to a safety analysis and found to be well tolerated and safe.


docid: eedynopo

title: Characterization of a Replicating and Packaged Defective RNA of Avian Coronavirus Infectious Bronchitis Virus

text: Abstract The Beaudette strain of IBV was passaged 16 times in chick kidney cells. Total cellular RNA was analyzed by Northern hybridization and was probed with 32 P-labeled cDNA probes corresponding to the first 2 kb of the 5′ end of the genome, but excluding the leader, and to the last 1.8 kb of the 3′ end of the genome. A new, defective IBV RNA species (CD-91) was detected at passage 6. The defective RNA, present in total cell extract RNA and in oligo-(dT)30-selected RNA from passage 15, was amplified by the reverse transcription-polymerase chain reaction (RT-PCR) to give four fragments. The oligonucleotides used were selected such that CD-91 RNA, but not the genomic RNA, would be amplified. Cloning and sequencing of the PCR products showed that CD-91 comprises 9.1 kb and has three regions of the genome. It contains 1133 nucleotides from the 5′ end of the genome, 6322 from gene 1b corresponding to position 12,423 to 18,744 in the IBV genome, and 1626 from the 3′ end of the genome. At position 749 one nucleotide, an adenine residue, was absent from CD-91 RNA. By Northern hybridization CD-91 RNA was detected in virions in higher amounts than the subgenomic mRNAs.


title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study

text: BACKGROUND: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. METHODS: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. RESULTS: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). CONCLUSIONS: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.


Of mice and men: defining, categorizing and understanding the significance of zoonotic infections


Reducing hospital admissions for COVID-19 at a dedicated Screening Centre in Singapore


Suivi des patients convalescents de la COVID-19 par le médecin généraliste


title: Interactions of Alphavirus nsP3 Protein with Host Proteins

text: Alphaviruses are members of the Togaviridae family and are grouped into two categories: arthritogenic and encephalitic. Arthritogenic alphavirus infections, as the name implies, are associated with arthritic outcomes while encephalitic alphavirus infections can lead to encephalitic outcomes in the infected host. Of the non-structural proteins (nsPs) that the viruses code for, nsP3 is the least understood in terms of function. Alphavirus nsP3s are characterized by regions with significantly conserved domain structure along with regions of high variability. Interactions of nsP3 with several host proteins have been documented including, stress granule-related proteins, dead box proteins, heat shock proteins, and kinases. In some cases, in addition to the interaction, requirement of the interaction to support infection has been demonstrated. An understanding of the proteomic network of nsP3 and the mechanisms by which these interactions support the establishment of a productive infection would make alphavirus nsP3 an interesting target for design of effective medical countermeasures.


title: Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves

text: BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.


title: Cellulose-based virus-retentive filters: a review

text: Viral filtration is a critical step in the purification of biologics and in the monitoring of microbiological water quality. Viral filters are also essential protection elements against airborne viral particles. The present review first focuses on cellulose-based filter media currently used for size-exclusion and/or adsorptive filtration of viruses from biopharmaceutical and environmental water samples. Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption–elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters. Viral analysis of field water samples by the viradel technique is also surveyed. This review then describes cellulose-based filter media used in individual protection equipment against airborne viral pathogens, presenting innovative filtration media with virucidal properties. Some pros and cons of cellulosic viral filters and perspectives for cellulose-based materials in viral filtration are underlined in the review.


title: Chapter 36 Identifying, Understanding, and Managing Patient Safety and Clinical Risks in the Clinical Research Environment

text: Abstract Meticulous study design, exacting scientific review, scrupulous data management, rigorous human subjects' protection, and effective recruitment strategies are essential components of all clinical research studies that must be in place prior to the conduct of the study. Equally important to the success of the study and to the well-being and protection of study participants is the assurance that safe clinical environments are provided for the care of research participants. This chapter describes approaches to managing patient care and clinical research quality, as well as the application of established health care-based clinical quality methods and tools to the complex processes of clinical research. Techniques for identifying clinical risks, tools for collecting data about the quality of clinical care processes, strategies for mitigating risk and patient harm, and techniques for measuring the participants' perceptions of the research process are discussed in detail.


title: Riniti e rinosinusiti acute dell’adulto

text: Le riniti e le rinosinusiti acute sono delle patologie frequenti e benigne nella maggior parte dei casi. La loro diagnosi è, prima di tutto, clinica. La difficoltà del loro trattamento è la differenziazione delle forme virali, più frequenti e banali, e delle forme batteriche, rare ma potenzialmente gravi. Le recenti raccomandazioni sono riassunte in questa esposizione. Analizzando le prove scientifiche del momento, esse insistono sui criteri diagnostici clinici, sulle indicazioni degli esami complementari, sull’efficacia dei vari trattamenti e sull’importanza dell’informazione e dell’educazione dei pazienti. I futuri lavori in questo settore dovranno permettere di selezionare in modo più preciso i pazienti che richiedono realmente una terapia antibiotica e di evitare, così, importanti spese sanitarie nonché la comparsa di ceppi batterici resistenti.


title: COVID-19 in an asymptomatic patient undergoing FDG PET/CT

text: 2019 novel coronavirus pneumonia (COVID-19) is an ongoing global pandemic with a worldwide death toll of over 416,000 as of June 10, 2020. Although the first documented cases in Wuhan, China were patients with severe respiratory symptoms including cough, fever, fatigue, and shortness of breath, the disease process can also be asymptomatic. In this case report, an asymptomatic 63-year old male with Lynch syndrome undergoing a routine staging fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) was found to have typical radiologic features of COVID-19 with marked pulmonary FDG uptake and was subsequently diagnosed via RT-PCR. Many studies have described the appearance of COVID-19 on chest radiography and CT with the most common imaging features being bilateral, peripheral, and basilar predominant ground glass opacities and consolidation. Although these findings are typically nonspecific for an atypical lung infection, early recognition of COVID-19 in the setting of a global pandemic (even in the asymptomatic patient) is critical in order to limit the spread of disease.


docid: ntynqlbp

title: A case report of a ruptured subclavian artery aneurysm presenting to the emergency department

text: Subclavian artery aneurysms are uncommon and present a diagnostic dilemma. Our patient attended with life‐threatening rupture, requiring prompt management. However, lack of on‐site facilities and specialist input posed a logistical challenge. The patient was stable enough to allow an urgent transfer to a specialist unit for successful endovascular repair.


title: The role of EMMPRIN in T cell biology and immunological diseases

text: EMMPRIN (CD147), originally described as an inducer of the expression of MMPs, has gained attention in its involvement in various immunologic diseases, such that anti‐EMMPRIN antibodies are considered as potential therapeutic medications. Given that MMPs are involved in the pathogenesis of various disease states, it is relevant that targeting an upstream inducer would make for an effective therapeutic strategy. Additionally, EMMPRIN is now appreciated to have multiple roles apart from MMP induction, including in cellular functions, such as migration, adhesion, invasion, energy metabolism, as well as T cell activation and proliferation. Here, we review what is known about EMMPRIN in numerous immunologic/inflammatory disease conditions with a particular focus on its complex roles in T cell biology.


Letter to the Editor Regarding Effects of the COVID-19 Outbreak in Northern Italy: Lessons Learned for African Neurosurgical Centers


title: Photonic Crystal Nanobeam Cavities for Nanoscale Optical Sensing: A Review

text: The ability to detect nanoscale objects is particular crucial for a wide range of applications, such as environmental protection, early-stage disease diagnosis and drug discovery. Photonic crystal nanobeam cavity (PCNC) sensors have attracted great attention due to high-quality factors and small-mode volumes (Q/V) and good on-chip integrability with optical waveguides/circuits. In this review, we focus on nanoscale optical sensing based on PCNC sensors, including ultrahigh figure of merit (FOM) sensing, single nanoparticle trapping, label-free molecule detection and an integrated sensor array for multiplexed sensing. We believe that the PCNC sensors featuring ultracompact footprint, high monolithic integration capability, fast response and ultrahigh sensitivity sensing ability, etc., will provide a promising platform for further developing lab-on-a-chip devices for biosensing and other functionalities.


title: Bacterial co-infection with H1N1 infection in patients admitted with community acquired pneumonia

text: Summary Background Bacterial co-infection is an important contributor to morbidity and mortality during influenza pandemics .We investigated the incidence, risk factors and outcome of patients with influenza A H1N1 pneumonia and bacterial co-infection. Methods Prospective observational study of consecutive hospitalized patients with influenza A H1N1 virus and community-acquired pneumonia (CAP). We compared cases with and without bacterial co-infection. Results The incidence of influenza A H1N1 infection in CAP during the pandemic period was 19% (n, 667). We studied 128 patients; 42(33%) had bacterial co-infection. The most frequently isolated bacterial pathogens were Streptococcus pneumoniae (26, 62%) and Pseudomonas aeruginosa (6, 14%). Predictors for bacterial co-infection were chronic obstructive pulmonary disease (COPD) and increase of platelets count. The hospital mortality was 9%. Factors associated with mortality were age ≥65 years, presence of septic shock and the need for mechanical ventilation. Although patients with bacterial co-infection presented with higher Pneumonia Severity Index risk class, hospital mortality was similar to patients without bacterial co-infection (7% vs. 11%, respectively, p = 0.54). Conclusion Bacterial co-infection was frequent in influenza A H1N1 pneumonia, with COPD and increased platelet count as the main predictors. Although associated with higher severe scales at admission, bacterial co-infection did not influence mortality of these patients.


title: The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization

text: Abstract Nucleocapsid protein plays a critical role in SARS-CoV pathogenesis, and high-level anti-nucleocapsid antibodies are detected in the patients infected by severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Several studies have shown that there exists an interaction between nucleocapsid (N) and membrane (M) protein. In this paper, we investigate whether the expression of membrane protein can affect the immune responses induced by nucleocapsid DNA immunization. Two recombinant plasmids containing M and N coding sequence were constructed. Moreover, in order to get the antigen for ELISA and in vitro stimulation assay, N protein were expressed and purified from E. coli bacteria. Injection of 20μg of the mixture of pVAX1-M and pVAX1-N into the Balb/c mice could elicit the humoral and cellular responses. The ELISA analysis using the N antigen or inactivated SARS-CoV particles as capture antigen showed that co-injection of SARS-M could enhance N-induced antibody production, especially IgG2a subclass. After lymphocytes were stimulated with 10μg/ml purified N antigen, The CD4+ and CD8+ T cells of N and M plus N group were increased compared with those of control groups, and the M protein could augment the activation of lymphocytes induced by N DNA vaccine. Cytokine ELISA analysis revealed that co-injection of M could enhance the levels of IFN-γ, IL-2 release induced by N antigen. Further experiments in field mouse also support the claim that membrane protein can augment the N-specific immune responses. Virus challenge test was conducted in BSL3 bio safety laboratory with Brandt's vole SARS-CoV model, and the results indicated that co-immunization of M and N antigens could reduce the mortality and pathological changes in lung from the virus infection.


title: The Effect of Dietary Energy Concentration on Calf Performance 1

text: Abstract At three locations, 120 calves were fed a high fat milk replacer at 10% of birth weight from d 5 through 13. On d 14, calves were assigned randomly within sex and date of birth to a 2 × 2 factorial arrangement of treatments. Treatments were (on a DM basis) high fat milk replacer (21.6%) and high fat starter (7.3%), high fat milk replacer (21.6%) and low fat starter (3.7%), low fat milk replacer (15.6%) and high fat starter (7.3%), and low fat milk replacer (15.6%) and low fat starter (3.7%). Milk replacer was fed at 8% of birth weight/d from d 14 to 35 and at 4% of birth weight/d from d 36 to 42. High fat replacer depressed DMI before and after weaning. High fat starter depressed DMI after weaning. Before weaning, calves gained more BW when fed low fat replacer. Calves fed low fat starter gained more BW after weaning. On d 56, BW were highest for calves fed low fat replacer and starter and lowest for those fed high fat replacer and starter. Growth or health of calves was not improved by fat addition to the diet.


The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus


The use of PET in COVID 19 cases


title: COVID-19 and the liver-related deaths to come

text: Coronavirus disease 2019 (COVID-19) itself and/or the use of hepatotoxic drugs might negatively affect the course and management of patients with pre-existing chronic liver diseases. However, the greatest effect of COVID-19 on liver diseases will be indirect and delayed, resulting from the impending global economic crisis.


title: Clinical study on the related markers of blood coagulation in the patients with ANFH after SARS

text: The aim of this research was to investigate the blood coagulation function in the patients with avascular necrosis of the femoral head (ANFH) after severe acute respiratory syndrome (SARS). The expression of CD31, CD61, CD62p, CD63 and PAC-1 on platelet membrane was measured respectively by flowcytometry, and the plasma prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (Fbg) were measured by blood clotting instrument in 26 patients with ANFH after SARS and in 17 healthy adults. The expression of CD31, CD61, CD 62p, CD63 and PAC-1 on platelet membrane in 26 patients was all lower than that in 17 healthy subjects (P < 0.01). The levels of PT, APTT, TT and Fbg in 26 patients were all normal. There is no significant difference (P > 0.05) in those markers between patients and 17 healthy adults. The blood may not be in hypercoagulable state in patients with ANFH after SARS.


title: Targeting potential drivers of COVID-19: Neutrophil extracellular traps

text: Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.


title: Griffithsin tandemers: flexible and potent lectin inhibitors of the human immunodeficiency virus

text: BACKGROUND: The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide. In addition to its broad antiviral activity, GRFT is stable at high temperature and at a broad pH range, displays little toxicity and immunogenicity, and is amenable to large-scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays. Previously, we have engineered and analyzed several monomeric forms of this lectin (mGRFT) with anti-HIV EC(50) values ranging up to 323 nM. Based on our previous analysis of mGRFT, we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity. RESULTS: Here we present data on engineered tandem repeats of mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed thermodynamically, both individually and in complex with HIV-1 gp120. We also demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT tandemers do not aggregate HIV virions. This establishes that, although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity, the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking. CONCLUSIONS: The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0127-3) contains supplementary material, which is available to authorized users.


Novel Bat Coronaviruses, Brazil and Mexico


A New Virulent Human Coronavirus: How Much Does Tissue Culture Tropism Tell Us?


title: Application of corona discharge-generated air ions for filtration of aerosolized virus and inactivation of filtered virus

text: Abstract The effect of corona discharge-generated air ions on the filtration of aerosolized bacteriophage MS2 was studied. A carbon-fiber ionizer was installed upstream of a medium-efficiency air filter to generate air ions, which were used to charge the virus aerosols and increase their filtration efficiency. After the virus aerosols were captured by the filter for a certain time interval, they were exposed to a newly incoming air ion flow. Captured virus particles were detached from the filter by sonication, and their antiviral efficiency due to air ions was calculated by counting the plaque-forming units. The antiviral efficiency increased with ion exposure time and ion concentration. When the concentration of positive air ions was 107 ions/cm3, the antiviral efficiencies were 46.1, 78.8, and 83.7% with exposure times of 15, 30, and 45min, respectively. When the ionizer was operated in a bipolar mode, the number concentrations of positive and negative ions were 6.6×106 and 3.4×106 ions/cm3, respectively, and the antiviral efficiencies were 64.3, 89.1, and 97.4% with exposure times of 15, 30, and 45min, respectively. As a quantitative parameter for the performance evaluation of air ions, the susceptibility constant of bacteriophage MS2 to positive, negative, bipolar air ions was calculated as 5.5×10−3, 5.4×10−3 and 9.5×10−3, respectively. These susceptibility constants showed bipolar ion treatment was more effective about 1.7 times than unipolar ion treatment.


title: Enhanced immune responses to viral epitopes by combining macrophage-inducible expression with multimeric display on a Salmonella vector

text: In this study, the immunogenicity of chimeric 987P fimbriae on a Salmonella vaccine strain was improved by optimizing fimbrial expression. The constitutive tetA promoter and the in vivo activated nirB and pagC promoters were evaluated for their use to express two epitopes of the transmissible gastroenteritis virus (TGEV) spike protein carried by fimbriae which were displayed on a Salmonella vaccine strain. Constructs with the pagC promoter were shown to drive increased expression of chimeric 987P fimbriae in macrophages as well as in Mg(2+)-poor media, mimicking a major environmental signal found in Salmonella-containing endocytic vacuoles of macrophages. Mice immunized orally with a Salmonella vaccine strain which expressed chimeric fimbriae from the pagC promoter elicited significantly higher mucosal and systemic immune responses to both the 987P fimbriae and the TGEV epitopes than mice immunized with the same strain hosting a tetA or nirB promoter-driven expression plasmid. Moreover, only the Salmonella vaccine strains harboring a plasmid with the pagC promoter, with or without an additional tetA promoter in tandem, elicited neutralizing antibodies to TGEV. This indicated that the pagC promoter can be used successfully to improve epitope-display by chimeric fimbriae on Salmonella vaccine strains for the induction of a desired immune response.


docid: bdmuszmf

title: Fear of COVID-19 and Positivity: Mediating Role of Intolerance of Uncertainty, Depression, Anxiety, and Stress

text: This study aimed to investigate the mediating role of intolerance of uncertainty, depression, anxiety, and stress in the relationship between the fear of COVID-19 and positivity. The participants consisted of 960 individuals, including 663 females (69.1%) and 297 males (30.9%). The age of the participants ranged between 18 and 76 (29.74 ± 9.64). As a result of the correlation analysis, a positive relationship was found between fear of COVID-19 and intolerance of uncertainty, depression, anxiety, and stress, and a negative relationship was determined between the fear of COVID-19 and positivity. The result of the analysis for the study model indicated that there was a mediating role of intolerance of uncertainty, depression, anxiety, and stress in the relationship between the fear of COVID-19 and positivity. Eliminating uncertainty from the fear of COVID-19 will contribute to reducing depression, anxiety and stress, and increasing positivity.


title: Wet markets—a continuing source of severe acute respiratory syndrome and influenza?

text: Summary Context Live-animal markets (wet markets) provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles, and mammals of every kind. Live-poultry markets (mostly chicken, pigeon, quail, ducks, geese, and a wide range of exotic wild-caught and farm-raised fowl) are usually separated from markets selling fish or red-meat animals, but the stalls can be near each other with no physical separation. Despite the widespread availability of affordable refrigeration, many Asian people prefer live animals for fresh produce. Wet markets are widespread in Asian countries and in countries where Asian people have migrated. Live-poultry markets were the source of the H5N1 bird-influenza virus that transmitted to and killed six of 18people in Hong Kong. Starting point Yi Guan and colleagues (Science 2003; 302: 276–78) recently reported the isolation of severe acute respiratory syndrome (SARS) coronavirus (CoV) from Himalayan palm civets (Paguna larvata) in wet markets in Shenzen, southern China. These researchers also found serological evidence of infection in raccoon dogs (Nyctereutes pro-cuyoinboides). Serological evidence for SARS CoV in human beings working in these markets, taken together with the earliest cases of SARS in restaurant workers, supports the contention of a potential zoonotic origin for SARS. Where next? Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.


title: A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry

text: Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens.


title: When altruists cannot help: the influence of altruism on the mental health of university students during the COVID-19 pandemic

text: BACKGROUND: The positive predictive effect of altruism on physical and psychological well-being has been extensively demonstrated in previous studies, but few studies have examined the effect of altruism on negative mental health outcomes when altruists cannot perform altruistic behaviours. This study explored the influence of altruism on negative affect and mental health (anxiety and depressive symptoms) during the COVID-19 pandemic while people self-isolated at home in China. METHOD: University students were recruited to participate in a cross-sectional online survey during the outbreak of COVID-19 in China. Self-reported perceived risk, altruism, negative affect, anxiety and depressive symptoms were measured using the Self-Report Altruism Scale (SRA scale), the Positive and Negative Affect Schedule (PANAS), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 9-item Patient Health Questionnaire depression scale (PHQ-9). A structural equation model was used to analyse the mediating and moderating effects on mental health. RESULTS: The final sample comprised 1346 Chinese participants (Mage = 19.76 ± 2.23 years, 73% female). Overall, the higher the risk the participants perceived, the more negative affect they exhibited (β = 0.16, p < .001), and thus, the more anxious and depressed they felt (β = 0.134, p < .001); however, this relationship between risk perception and negative affect was moderated by altruism. In contrast to previous studies, the increase in negative affect associated with the increased perceived risk was pronounced among individuals with high altruism (t = 7.68, p < .001). CONCLUSIONS: Individuals with high altruism exhibited more negative affect than those with low altruism, which indirectly increased their anxiety and depressive symptoms. These findings enrich theories of altruism and provide valuable insight into the influence of altruism on mental health during the COVID-19 outbreak.


title: Communicable Diseases and Outbreak Control

text: Infectious disease during an emergency condition can raise the death rate 60 times in comparison to other causes including trauma. An epidemic, or outbreak, can occur when several aspects of the agent (pathogen), population (hosts), and the environment create an ideal situation for spread. Overcrowding, poor regional design and hygiene due to poverty, dirty drinking water, rapid climate changes, and natural disasters, can lead to conditions that allow easier transmission of disease. Once it has been established that an emergency condition exists, there must be a prompt and thorough response for communicable disease control. A camp should be created, and the disease managed rapidly. The overall goals are rapid assessment, prevention, surveillance, outbreak control, and disease management.


title: Respiratory viral panels and pediatric airway evaluation: the role of testing for upper respiratory infections to stratify perioperative risk

text: Abstract Objectives Children admitted with stridor and respiratory distress comprise a complex patient group that requires the otolaryngologist to decide when to assess and intervene with direct laryngoscopy and bronchoscopy (DLB). Historically, the diagnosis of viral upper respiratory tract infection (URTI) can lead to postponement of surgery due to concerns of perioperative complications related to acute illness. Respiratory viral panels (RVP) are often used to confirm the presence of recent or active viral infection and can affect the differential diagnosis of upper airway obstruction. This study examined whether RVP positive testing is correlated with perioperative complications and operative findings in pediatric patients undergoing inpatient DLB. Methods A retrospective chart review of 132 pediatric patient encounters was performed. Viral testing results, DLB indication, DLB findings, and perioperative complications were compared. Results Sixty encounters (45.5%) involved a positive RVP, and 72 (54.5%) involved a negative RVP. Those with positive RVP were less likely to have an anatomic airway abnormality (p = 0.0250) and more likely to have a history of recurrent upper respiratory infections (p = 0.0464). The most common reason for DLB was to assess for structural airway abnormality. Laryngospasm occurred in 1 (1.7%) RVP positive and 1 (1.4%) RVP negative encounter, and 2 (2.8%) RVP negative encounters required reintubation. No other major complications were observed. No association was noted between RVP results and incidence of major or minor complication. Conclusions Major perioperative complications after surgical intervention with DLB for the management of complex, inpatient children with stridor and respiratory distress are rare. RVP positivity, specific pathogens identified on RVP, and presence of URI symptoms were not associated with perioperative complications.


The Forrest Gump approach to preventing severe COVID-19 – reverse the predisposing pro-inflammatory state with exercise


title: A Consensus Action Agenda for Achieving the National Health Information Infrastructure

text: Background: Improving the safety, quality, and efficiency of health care will require immediate and ubiquitous access to complete patient information and decision support provided through a National Health Information Infrastructure (NHII). Methods: To help define the action steps needed to achieve an NHII, the U.S. Department of Health and Human Services sponsored a national consensus conference in July 2003. Results: Attendees favored a public–private coordination group to guide NHII activities, provide education, share resources, and monitor relevant metrics to mark progress. They identified financial incentives, health information standards, and overcoming a few important legal obstacles as key NHII enablers. Community and regional implementation projects, including consumer access to a personal health record, were seen as necessary to demonstrate comprehensive functional systems that can serve as models for the entire nation. Finally, the participants identified the need for increased funding for research on the impact of health information technology on patient safety and quality of care. Individuals, organizations, and federal agencies are using these consensus recommendations to guide NHII efforts.


title: Can an evidence-based guideline reminder card improve asthma management in the emergency department?

text: Summary Objective Asthma is the most common chronic disease in children. Previous studies described significant variations in acute asthma management in children. This study was conducted to examine whether asthma management in the pediatric emergency department (ED) was improved through the use of an evidence-based acute asthma care guideline reminder card. Methods The Pediatric Acute Asthma Management Guideline (PAMG) was introduced to the ED of a pediatric tertiary care hospital in Ontario, Canada. Medical charts of 278 retrospective ED visits (January–December 2002) and 154 prospective visits (July 2003–June 2004) were reviewed to assess changes in acute asthma management such as medication treatment, asthma education, and discharge planning. Logistic and linear regressions were used to determine the effect of PAMG on asthma management in the ED. The propensity score method was used to adjust for confounding. Results During the implementation of PAMG, patients who visited the ED were more likely to receive oral corticosteroids (Adjusted Odds Ratio [AOR] = 2.26, 95% CI: 1.63–3.14, p < 0.0001) and oxygen saturation reassessment before ED discharge (AOR = 2.02, 95% CI: 1.45–2.82, p < 0.0001). They also received 0.23 (95% CI: 0.03–0.44, p = 0.0283) more doses of bronchodilator in the first hour of ED stay. Improvements in asthma education and discharge planning were noted, but the changes were not statistically significant. Conclusions After the implementation of an evidence-based guideline reminder card, medication treatment for acute asthma in the ED was significantly improved; however, asthma education and discharge planning remained unchanged. Future efforts on promoting guideline-based practice in the ED should focus on these components.


title: Travel implications of emerging coronaviruses: SARS and MERS-CoV

text: Summary The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and of the Middle East Syndrome Cornavirus (MERS-CoV) caused widespread fear and concern for their potential threat to global health security. There are similarities and differences in the epidemiology and clinical features between these two diseases. The origin of SARS-COV and MERS-CoV is thought to be an animal source with subsequent transmission to humans. The identification of both the intermediate host and the exact route of transmission of MERS-CoV is crucial for the subsequent prevention of the introduction of the virus into the human population. So far MERS-CoV had resulted in a limited travel-associated human cases with no major events related to the Hajj.


COVID‐19 in a child with severe aplastic anemia


Questioning the Value of the Graduate Record Examinations (GRE) in PhD Admissions in Biomedical Engineering


title: Cytokines and synthetic double-stranded RNA augment the T helper 1 immune response of swine to porcine reproductive and respiratory syndrome virus

text: Abstract Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-γ response. To improve the immune response, an adjuvant consisting of plasmid encoding either porcine interleukin (IL)-12 or IFN-α was co-administered during vaccination. In the presence of either adjuvant, at least a three-fold increase in the primary virus-specific IFN-γ response was observed. While this enhancement was only transient (1 week) when the IL-12 expressing plasmid was used, the effect was not only still apparent at 6 weeks after vaccination in the presence of the IFN-α expressing plasmid but even after challenge with a virulent genetically divergent PRRSV. In contrast, no effect of either adjuvant on the production of anti-virus antibodies was noticed throughout the study. Despite the apparent augmentation of a T helper (Th) 1 type response by the inclusion of IFN-α or IL-12 during vaccination, this modulation did not necessarily correlate with a reduction in viremia. Since a similar increase in the degree of the IFN-γ response to the PRRSV vaccine could be achieved by substituting polyinosinic–polycytidylic acid in lieu of either cytokine, exposure to PRRSV in the presence of a variety of Th 1 polarizing molecules can positively influence the development of the cell-mediated immune response of swine to this pathogen. Conceivably, such intervention could be applied to improve the formulation of anti-PRRSV vaccines.


title: Lactic acid bacteria efficiently protect human and animal intestinal epithelial and immune cells from enteric virus infection

text: Abstract This study aimed to examine the potential antiviral activity of lactic acid bacteria (LAB) using animal and human intestinal and macrophage cell line models of non tumor origin. To this end, LAB strains selected on the basis of previous in vitro trials were co-incubated with cell line monolayers, which were subsequently challenged with rotavirus (RV) and transmissible gastroenteritis virus (TGEV). In order to elucidate the possible mechanism responsible for the antiviral activity, the induction of reactive oxygen species (ROS) release as well as the attachment ability of LAB on the cell lines was investigated. Various strains were found to exhibit moderate to complete monolayer protection against viral RV or TGEV disruption. Highest protection effects were recorded with the known probiotics Lactobacillus rhamnosus GG and Lactobacillus casei Shirota against both RV and TGEV, while notable antiviral activity was also attributed to Enterococcus faecium PCK38, Lactobacillus fermentum ACA-DC179, Lactobacillus pentosus PCA227 and Lactobacillus plantarum PCA236 and PCS22, depending on the cell line and virus combination used. A variable increase (of up to 50%) on the release of NO− and H2O2 (ROS) was obtained when LAB strains were co-incubated with the cell lines, but the results were found to be LAB strain and cell line specific, apart from a small number of strains which were able to induce strong ROS release in more than one cell line. In contrast, the ability of the examined LAB strains to attach to the cell line monolayers was LAB strain but not cell line specific. Highest attachment ability was observed with L. plantarum ACA-DC 146, L. paracasei subsp. tolerans ACA-DC 4037 and E. faecium PCD71. Clear indications on the nature of the antiviral effect were evident only in the case of the L. casei Shirota against TGEV and with L. plantarum PCA236 againt both RV and TGEV. In the rest of the cases, each interaction was LAB-cell line–virus specific, barring general conclusions. However, it is probable that more than one mechanism is involved in the antiviral effect described here. Further investigations are required to elucidate the underlying mode of action and to develop a cell line model as a system for selection of probiotic strains suited for farm animal applications.


title: A quantitative enzyme-linked immunosorbent assay for bovine herpesvirus type 1 (BHV-1) antibody

text: Abstract A quantitative enzyme-linked immunosorbent assay (ELISA) was developed to detect and measure antibody to bovine herpesvirus type 1 (BHV-1) in cattle sera. The optical density produced from a single dilution of test serum was compared with a standard curve and the results were read and printed out from a computer interfaced to a multichannel ELISA reader. The printed results were expressed in ELISA units. The ELISA results obtained on 370 cattle sera were compared with those of the serum neutralisation test (SNT). An agreement of 90·5% was obtained when reciprocal SNT titres equal to or greater than 4 and IgG ELISA units equal to or greater than 50 were taken as indicative of a specific reaction. Of the 370 sera, 35 gave discrepant results of which 21 were SNT positive/IgG ELISA negative and 14 were SNT negative/IgG ELISA positive. When the SNT positive sera negative in the IgG ELISA were tested in an IgM ELISA, 19 were found to be positive. Thus, when the IgG and IgM ELISA results were combined the overall agreement between the ELISA and SNT increased to 95·7%. The IgG ELISA had a sensitivity of 82·4% and specificity of 94·4% relative to the SNT, whereas the combined IgG and IgM ELISA results gave a sensitivity and specificity of 98·3% and 94·4% respectively. There was a good positive correlation between the two tests (r = 0·86).


title: Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies.


title: Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling

text: Abstract Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of lipid peroxidizing enzymes and human lipoxygenase isoforms have been implicated in the pathogenesis of inflammatory, hyperproliferative (cancer) and neurodegenerative diseases. Lipoxygenases are not restricted to humans but also occur in a large number of pro- and eucaryotic organisms. Lipoxygenase-like sequences have been identified in the three domains of life (bacteria, archaea, eucarya) but because of lacking functional data the occurrence of catalytically active lipoxygenases in archaea still remains an open question. Although the physiological and/or pathophysiological functions of various lipoxygenase isoforms have been studied throughout the last three decades there is no unifying concept for the biological importance of these enzymes. In this review we are summarizing the current knowledge on the distribution of lipoxygenases in living single and multicellular organisms with particular emphasis to higher vertebrates and will also focus on the genetic diversity of enzymes and receptors involved in human leukotriene signaling.


docid: ndfoppoq

title: Airborne or droplet precautions for health workers treating COVID-19?

text: Cases of COVID-19 have been reported in over 200 countries. Thousands of health workers have been infected and outbreaks have occurred in hospitals, aged care facilities and prisons. World Health Organization (WHO) has issued guidelines for contact and droplet precautions for Healthcare Workers (HCWs) caring for suspected COVID-19 patients, whilst the US Centre for Disease Control (CDC) has recommended airborne precautions. The 1 – 2 m (≈3 – 6 ft) rule of spatial separation is central to droplet precautions and assumes large droplets do not travel further than 2 m (≈6 ft). We aimed to review the evidence for horizontal distance travelled by droplets and the guidelines issued by the World Health Organization (WHO), US Center for Diseases Control (CDC) and European Centre for Disease Prevention and Control (ECDC) on respiratory protection for COVID-19. We found that the evidence base for current guidelines is sparse, and the available data do not support the 1 – 2 m (≈3 – 6 ft) rule of spatial separation. Of ten studies on horizontal droplet distance, eight showed droplets travel more than 2 m (≈6 ft), in some cases more than 8 meters (≈26 ft). Several studies of SARS-CoV-2 support aerosol transmission and one study documented virus at a distance of 4 meters (≈13 ft) from the patient. Moreover, evidence suggests infections cannot neatly be separated into the dichotomy of droplet versus airborne transmission routes. Available studies also show that SARS-CoV-2 can be detected in the air, 3 hours after aeroslisation. The weight of combined evidence supports airborne precautions for the occupational health and safety of health workers treating patients with COVID-19.


title: Response to Commentary on “The neuroinvasive potential of SARS‐CoV‐2 may play a role in the respiratory failure of COVID‐19 patients”

text: In a recent review, we have suggested a neuroinvasive potential of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its possible role in the causation of acute respiratory failure of coronavirus disease 2019 (COVID‐19) patients (J Med Viol doi: 10.1002/jmv.25728), based upon the clinical and experimental data available on the past SARS‐CoV‐1 and the recent SARS‐CoV‐2 pandemic. In this article, we provide new evidence recently reported regarding the neurotropic potential of SARS‐CoV‐2 and respond to several comments on our previously published article. In addition, we also discuss the peculiar manifestations of respiratory failure in COVID‐19 patients and the possible involvement of nervous system.


title: Distinct features of SARS-CoV-2-specific IgA response in COVID-19 patients

text: Humoral immune response to SARS-CoV-2 showed an early response of IgA, instead of IgM, in COVID-19 patients. As highlighted by our study, enhanced IgA responses observed in severe COVID-19 might confer damaging effects in severe COVID-19.


docid: jelphtyn

title: The use of red cells with fused Semliki Forest virus envelope proteins in antibody determinations by hemolysis in gel

text: Abstract Chicken red blood cells with fused Semliki Forest virus (SFV) proteins on the cell membrane were used in the hemolysis-in-gel (HIG) plates. Optimally the plate contained a 1.5 mm thick gel of 1% agarose with 1% red cells and 1 unit/ml gel of complement. 400 ng of SFV was fused to the red cells in 1 ml of the gel (about 20 virions fused to one red cell). Five μl of inactivated (56°C, 30 min) serum samples were pipetted into wells in the gel. After 20 h of incubation at 37°C the diameters of the hemolytic zones were directly proportional to the logarithm of the serum dilution. This made it possible to calculate the antibody titers for the samples using an experimental formula T = 10 φ k (T is the titer, φ the diameter in mm and k a variable coefficient, which had to be determined for each batch of the plates using a standard serum). Using regression and residual analyses, the formula was shown to fit the experimental results. The fusion-based HIG could be read after as early as 2 h of incubation. The specificity of the test was studied using antisera against Western equine encephalomyelitis, Eastern equine encephalomyelitis, Chikungunya and Uruma viruses, which all gave negative results in the SFV HIG test. Antisera against SFV E1 and E2 proteins were positive, but anti-E3 serum was negative when measured in the SFV HIG test.


COVID-19 mimicking ST-elevation myocardial infarction


title: Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis

text: Abstract The behavior and myelinogenic properties of glial cells have been well documented following transplantation into regions of focal experimental demyelination in animal models. However, the ability of glial cell preparations to remyelinate in such models does not necessarily indicate that their transplantation into demyelinated lesions in clinical disease will be successful. One of the precluding factors in this regard is a greater understanding of the environmental conditions that will support transplant-mediated remyelination. In this study, we determined whether the complex and reactive CNS environment of the mouse hepatitis virus (MHV) model of multiple sclerosis (MS) could support transplant-mediated remyelination. Striatal neural precursors derived from postnatal day 1 mice were committed to a glial cell lineage and labeled. Immunohistochemical staining indicated that this population generated >93% glial cells following differentiation in vitro. Transplantation of glial-committed progenitor cells into the T8 spinal cord of MHV-infected mice demonstrating complete hindlimb paralysis resulted in migration of cells up to 12 mm from the implantation site and remyelination of up to 67% of axons. Transplanted-remyelinated animals contained approximately 2× the number of axons within sampled regions of the ventral and lateral columns as compared to non-transplanted animals, suggesting that remyelination is associated with axonal sparing. Furthermore, transplantation resulted in behavioral improvement. This study demonstrates for the first time that transplant-mediated remyelination is possible in the pathogenic environment of the MHV demyelination model and that it is associated with locomotor improvement.


title: Chapter 6 Conservation Genetics of the Cheetah: Genetic History and Implications for Conservation

text: Abstract From allozymes in 1983 to whole genomes in 2015, genetic studies of the cheetah have been extensive. In this chapter we provide an overview of the available literature. Overall, patterns of genetic variation provided evidence of low variability and suggest this loss occurred thousands of years ago. Differences between published subspecies were supported genetically. At a local scale, populations were generally considered panmictic with minor genetic structure. Although cheetahs have persisted despite low genetic variability, important questions arise from these findings: Does the cheetah have the ability to adapt to and evolve with future changes in environmental and infectious pressure? How would cheetahs cope with further loss of genetic diversity? Connectivity in the wild should be maintained via prevention of habitat loss, while management of small isolated populations may require reestablishing gene flow. Genetics could assist captive-breeding decisions and provide forensic evidence as to the geographical origin of illegally traded animals.


docid: uwyiplyg

title: Impact of supplementary private health insurance on hospitalization and physical examination in China

text: Abstract Private health insurance (PHI) is considered an important supplement to the basic social health insurance schemes in the Chinese healthcare system. However, whether the strategy of engaging PHI as supplementary coverage is effective cannot be determined without knowing the impact of supplementary PHI on healthcare access and utilization, the evidence on which is currently absent in China. Therefore, we aimed to investigate the effects of supplementary PHI on hospitalization and physical examination to provide such evidence in the Chinese setting. We conducted a cross-sectional analysis using data from the 2015 wave of China Health and Retirement Longitudinal Study (CHARLS). Using probit models and bivariate probit models with instrumental variables (IVs), we evaluated the effects of supplementary PHI on the utilization of hospitalization and physical examination. Our analyses provided evidence that supplementary PHI increased the probability of physical examination but decreased that of hospitalization. Our findings suggest that supplementary PHI in China may effectively promote the use of high-value preventive care, thereby reducing subsequent utilization of expensive medical services. The present study provided preliminary evidence that the China healthcare system can benefit from engaging PHI as supplements to SHI.


title: Testing the repatriated for SARS-Cov2: Should laboratory-based quarantine replace traditional quarantine?

text: Abstract Background An ongoing epidemic of respiratory diseases caused by a novel coronavirus (COVID 2019, SARS-CoV2) started in Wuhan, Hubei, in China at the end of December 2019. The French government decided to repatriate the 337 French nationals living in Wuhan and place them in quarantine in their home country. We decided to test them all for SARS-Cov2 twice in order to reduce anxiety among the population and decision-makers. Methods We investigated the presence of SARS-CoV-19 in asymptomatic carriers by testing all repatriated patients within the first 24 h of their arrival in France and at day 5. Viral RNA was extracted from pooled nasal and oropharyngeal swab fluids or sputum in the absence of nasal/oropharyngeal swabs. Detection of SARS-CoV-2 RNA was then carried out using several real-time reverse transcription (RT)-PCR assays. Results We tested 337 passengers at day 0 and day 5. All the tests for SARS-CoV2 were negative. By optimising the sampling process, sending samples sequentially and reducing the time-scale for biological analysis, we were able to test the samples within 5 h (including sampling, shipment and biological tests). Conclusion Optimising our procedures reduces anxiety and reassures the population and decision makers.


title: Foot and ankle service adaptation in response to COVID-19 and beyond

text: The disruption to healthcare provision as a result of the COVID-19 pandemic has compelled us to streamline healthcare delivery. This has given us an opportunity to implement healthcare technology, reform inter-disciplinary collaboration and ultimately enhance patient care. We discuss some of the advances made by the foot and ankle department at our hospital. These innovations have broad applicability and will hopefully ignite discussion amoung a number of healthcare teams about improving the future care of their patients.


title: COVID-19, extractive industries, and indigenous communities in Canada: Notes towards a political economy research agenda

text: As the economic ramifications of the COVID-19 pandemic continue to unfold, it is becoming increasingly apparent that this crisis will have significant and lasting implications for the relationship between extractive industries and Indigenous communities. Using a case study from Canada, this paper examines how the political dynamics of industry-Indigenous relations have changed and speculates about how these dynamics might continue to change in the future. The economic crisis has already intensified political conflicts and struggles between Indigenous peoples and mining, oil, and gas companies. We identify and discuss four points of conflict between Indigenous communities and extractive industries that have become more acute as a result of the current economic crisis. It is important for researchers to pay close attention to how these conflicts are affected by the pandemic, in order to help Indigenous communities develop strategies to cope with changes in industry-Indigenous relations.


Evolution of Cancer Care in Response to the COVID‐19 Pandemic


The fight against COVID-19: disinfection protocol and turning over of CleanSpace(®) HALO™ in a Singapore Hospital


title: Experimental rhinovirus infection in COPD: Implications for antiviral therapies

text: Abstract Chronic obstructive pulmonary disease (COPD) is a major public health problem and will be one of the leading global causes of mortality over the coming decades. Much of the morbidity, mortality and health care costs of COPD are attributable to acute exacerbations, the commonest causes of which are respiratory infections. Respiratory viruses are frequently detected in COPD exacerbations but direct proof of a causative relationship has been lacking. We have developed a model of COPD exacerbation using experimental rhinovirus infection in COPD patients and this has established a causative relationship between virus infection and exacerbations. In addition it has determined some of the molecular mechanisms linking virus infections to COPD exacerbations and identified potential new therapeutic targets. This new data should stimulate research into the role of antiviral agents as potential treatments for COPD exacerbations. Testing of antiviral agents has been hampered by the lack of a small animal model for rhinovirus infection and experimental rhinovirus infection in healthy volunteers has been used to test treatments for the common cold. Experimental rhinovirus infection in COPD subjects offers the prospect of a model that can be used to evaluate the effects of new treatments for virus-induced COPD exacerbations, and provide essential data that can be used in making decisions regarding large scale clinical trials.


title: Animal models for the risk assessment of viral pandemic potential

text: Pandemics affect human lives severely and globally. Experience predicts that there will be a pandemic for sure although the time is unknown. When a viral epidemic breaks out, assessing its pandemic risk is an important part of the process that characterizes genomic property, viral pathogenicity, transmission in animal model, and so forth. In this review, we intend to figure out how a pandemic may occur by looking into the past influenza pandemic events. We discuss interpretations of the experimental evidences resulted from animal model studies and extend implications of viral pandemic potentials and ingredients to emerging viral epidemics. Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses.


SPONTANEOUS MAJOR HEMORRHAGE IN COVID-19 PATIENTS: ANOTHER BRICK IN THE WALL OF SARS COV 2-ASSOCIATED COAGULATION DISORDERS?


The Potential Beneficial Effect of EPA and DHA Supplementation Managing Cytokine Storm in Coronavirus Disease


title: The Isolation, Pathogenesis, Diagnosis, Transmission, and Control of Avian Bornavirus and Proventricular Dilatation Disease

text: Proventricular dilatation disease (PDD) is a common infectious neurologic disease of birds comprising a dilatation of the proventriculus by ingested food as a result of defects in intestinal motility, which affects more than 50 species of psittacines, and is also known as Macaw wasting disease, neuropathic ganglioneuritis, or lymphoplasmacytic ganglioneuritis. Definitive diagnosis of PDD has been problematic due to the inconsistent distribution of lesions. Since its discovery, avian bornavirus (ABV) has been successfully cultured from the brains of psittacines diagnosed with PDD, providing a source of antigen for serologic assays and nucleic acid for molecular assays. This article provides evidence that ABV is the etiologic agent of PDD. Recent findings on the transmission, epidemiology, pathogenesis, diagnosis, and control of ABV infection and PDD are also reviewed.


Hydroxychloroquine and ivermectin: a synergistic combination for COVID-19 chemoprophylaxis and/or treatment?


title: The Use and Benefit of Adjuvant Radiotherapy in Parathyroid Carcinoma: A National Cancer Database Analysis

text: BACKGROUND: The routine use of external beam radiotherapy (EBRT) is not recommended for parathyroid carcinoma (PC). However, case series have demonstrated a potential benefit in preventing local recurrence with EBRT. We aimed to characterize the patient population treated with EBRT and identify any impact of EBRT on overall survival (OS) in parathyroid carcinoma. METHODS: Patients who underwent surgery for PC from 2004 to 2016 were identified from the National Cancer Database. Clinicopathologic variables and OS were compared between patients based on treatment with EBRT. Multivariable logistic and Cox regression models were performed with propensity scores and inverse-probability-weighting (IPW) adjustment to reduce treatment-selection bias in the OS analysis. RESULTS: A total of 885 patients met the inclusion criteria, with 126 (14.2%) undergoing EBRT. Demographics were similar between the two cohorts (EBRT vs. no EBRT). However, patients treated with EBRT had a higher frequency of regionally extensive disease, nodal metastases, and residual microscopic disease (all p < 0.05). On multivariable analysis, Black race, regional tumor extension, nodal metastasis, and treatment at an urban facility were independently associated with EBRT. The 5-year OS was 85.3% with a median follow-up of 60.8 months. EBRT was not associated with a difference in OS in crude, multivariable, or IPW models. More importantly, 10.5% of patients with completely resected localized disease (M0, N0 or Nx) underwent EBRT without a benefit in OS (p = 0.183). CONCLUSIONS: EBRT is not associated with any survival benefit in the treatment of PC. Therefore, it may be overutilized, particularly in patients with localized disease and complete surgical resection.


title: SARS in Singapore: surveillance strategies in a globalising city

text: Abstract Public health measures employed to fight against the spread of SARS need to be guided by biomedical knowledge as well as an understanding of the social science aspects of the disease. Using Singapore as a case study, we explore how the state constructs the disease and implements measures targeted at creating a ring of defense around the island and using surveillance to monitor and prevent its spread. While there is support, there is also resentment among some Singaporeans who complain that their right to privacy has been invaded and that over surveillance may have actually occurred. Marginalisation and discrimination have not only affected the local population but in this open economy which is striving to achieve global city status, businesses, tourism, foreign talent, foreign contract workers and foreign students studying in Singapore have also been negatively affected. While Singapore has been applauded by WHO and used as an example of quick and effective response, a holistic approach to the management of infectious disease must address the social implications of strategies that are drawn from medical knowledge alone because it impinges on the social lives of people and how people interact with each other under stressful circumstances.


title: Model or meal? Farm animal populations as models for infectious diseases of humans

text: In recent decades, theory addressing the processes that underlie the dynamics of infectious diseases has progressed considerably. Unfortunately, the availability of empirical data to evaluate these theories has not grown at the same pace. Although laboratory animals have been widely used as models at the organism level, they have been less appropriate for addressing issues at the population level. However, farm animal populations can provide empirical models to study infectious diseases at the population level.


title: Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China

text: Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for controlling antimicrobial resistance in healthcare settings at an administrative level.


SARS-CoV-2 Human Challenge Trials: Too Risky, Too Soon


COVID-19 pandemic and the social effects on clinic and scientific research: the “human factor”


title: Biodistribution, persistence and lack of integration of a multigene HIV vaccine delivered by needle-free intradermal injection and electroporation

text: It is likely that gene-based vaccines will enter the human vaccine area soon. A few veterinary vaccines employing this concept have already been licensed, and a multitude of clinical trials against infectious diseases or different forms of cancer are ongoing. Highly important when developing novel vaccines are the safety aspects and also new adjuvants and delivery techniques needs to be carefully investigated so that they meet all short- and long-term safety requirements. One novel in vivo delivery method for plasmid vaccines is electroporation, which is the application of short pulses of electric current immediately after, and at the site of, an injection of a genetic vaccine. This method has been shown to significantly augment the transfection efficacy and the subsequent vaccine-specific immune responses. However, the dramatic increase in delivery efficacy offered by electroporation has raised concerns of potential increase in the risk of integration of plasmid DNA into the host genome. Here, we demonstrate the safety and lack of integration after immunization with a high dose of a multigene HIV-1 vaccine delivered intradermally using the needle free device Biojector 2000 together with electroporation using Derma Vax™ DNA Vaccine Skin Delivery System. We demonstrate that plasmids persist in the skin at the site of injection for at least four months after immunization. However, no association between plasmid DNA and genomic DNA could be detected as analyzed by qPCR following field inversion gel electrophoresis separating heavy and light DNA fractions. We will shortly initiate a phase I clinical trial in which healthy volunteers will be immunized with this multiplasmid HIV-1 vaccine using a combination of the delivery methods jet-injection and intradermal electroporation.


docid: lzvtgwox

title: Antigenic variation among bovine enteric coronaviruses (BECV) and bovine respiratory coronaviruses (BRCV) detected using monoclonal antibodies

text: Bovine coronavirus (BCV) causes neonatal calf diarrhea (CD) and is associated with winter dysentery (WD) in adult dairy cattle. It can also be isolated from the respiratory tracts of cattle entering feedlots. Monoclonal antibodies (MAbs) specific for the hemagglutinin esterase (HE) and spike (S) surface proteins of 2 bovine enteric coronavirus (BECV) strains and two bovine respiratory coronavirus (BRCV) strains were tested against 6 BECV strains and 6 recently isolated BRCV strains, in order to characterize the antigenicity of BCV strains with varied tissue tropisms. All MAbs had high immunofluorescence (IF) titers against BECV and BRCV strains, indicative of conserved cross-reactive epitopes. In hemagglutination inhibition (HI) tests, the S-MAbs were more broadly reactive than HE-MAbs. The BRCV and CD MAbs were more broadly reactive in HI than the WD MAbs. The HA activity of the Mebus vaccine CD strain was not inhibited by any of the MAbs tested. The HI activity of BRCV strain R6 was unique among the 6 BRCV isolates. In virus neutralization assays, MAbs to the BRCV strain R4 neutralized all 6 BECV strains tested. Antigenic variation exists among both BECV and BRCV strains, but it cannot be attributed soley to the clinical origin of the strain.


Facial mask: A necessity to beat COVID-19


title: Ochratoxin A promotes porcine circovirus type 2 replication in vitro and in vivo

text: Abstract Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin in animals and humans. Porcine circovirus-associated disease (PCVAD), including porcine dermatitis and nephropathy syndrome, is a worldwide swine disease. To date, little is known concerning the relationship between OTA and porcine circovirus type 2 (PCV2), the primary causative agent of PCVAD. The effects of OTA on PCV2 replication and their mechanisms were investigated in vitro and in vivo. The results in vitro showed that low doses of OTA significantly increased PCV2 DNA copies and the number of infected cells. Maximum effects were observed at 0.05μg/ml OTA. The results in vivo showed that PCV2 replication was significantly increased in serum and tissues of pigs fed 75μg/kg OTA compared with the control group and pigs fed 150μg/kg OTA. In addition, low doses of OTA significantly depleted reduced glutathione and mRNA expression of NF-E2-related factor 2 and γ-glutamylcysteine synthetase; increased reactive oxygen species, oxidants, and malondialdehyde; and induced p38 and ERK1/2 phosphorylation in PK15 cells. Adding N-acetyl-l-cysteine reversed the changes induced by OTA. Knockdown of p38 and ERK1/2 by their respective specific siRNAs or inhibition of p38 and ERK1/2 phosphorylation by their respective inhibitors (SB203580 and U0126) eliminated the increase in PCV2 replication induced by OTA. These data indicate that low doses of OTA promoted PCV2 replication in vitro and in vivo via the oxidative stress-mediated p38/ERK1/2 MAPK signaling pathway. This suggests that low doses of OTA are potentially harmful to animals, as they enhance virus replication, and partly explains why the morbidity and severity of PCVAD vary significantly in different pig farms.