niryuu/sni-each-converted huggingface dataset:
Background: During natural and manmade disasters, the hospital is perceived as a central rallying and care site for the public, for both those with and without emergency medical needs. The expectations of the public may outstrip hospital plans and abilities to provide nonmedical assistance. Objective: Our objective was to determine the public expectations of the hospital during disasters regarding resource provision. Methods: A survey was distributed to adult patients or family members at three emergency departments (EDs). Respondents were asked to evaluate hospital responsibility to provide nine resources to those without emergency medical needs, including vaccination, medication refill or replacement, food and water, grief/stress counseling, Federal Emergency Management Agency (FEMA) access assistance, short/long-term shelter, family reunification, and hospital. Additionally, respondents answered questions regarding prior disaster experience and demographics. Results: There were 961 respondents (66.9% were female, 47.5% were white, and 44.6% were black). Respondents agreed or strongly agreed that the hospital should provide the following services: event-specific vaccination (84%), medication refill/replacement (76.5%), food and water (61%), grief or stress counseling (53%), FEMA access assistance (52%), short-term shelter (51%), family reunification (50%), long-term shelter (38%), and hospital transportation (29%). Those 36-45 years of age were less likely to expect services (p < 0.05) and nonwhites and those with a family member with a medical condition requiring electricity were more likely to expect services (p < 0.001 and p < 0.05, respectively). There were no differences based on frequency of ED use, sex, income, or prior disaster experience. Conclusion: There is a high public expectation that hospitals will provide significant nonmedical disaster relief. Understanding these expectations is essential to appropriate community disaster planning. Ó 2013 Elsevier Inc.
Output: Selected Topics: Disaster Medicine PUBLIC PERCEPTIONS OF HOSPITAL RESPONSIBILITIES TO THOSE PRESENTING WITHOUT MEDICAL INJURY OR ILLNESS DURING A DISASTER
Dietary fish oils, rich in (n-3) PUFA, including eicosapentaenoic acid and docosahexaenoic acid, have been shown to have antiinflammatory properties. Although the antiinflammatory properties of fish oil may be beneficial during a chronic inflammatory illness, the same antiinflammatory properties can suppress the inflammatory responses necessary to combat acute viral infection. Given that (n-3) fatty acid-rich fish oil supplementation is on the rise and with the increasing threat of an influenza pandemic, we tested the effect of fish oil feeding for 2 wk on the immune response to influenza virus infection. Male C57BL/6 mice fed either a menhaden fish oil/corn oil diet (4 g fish oil:1 g corn oil, wt:wt at 5 g/100 g diet) or a control corn oil diet were infected with influenza A/PuertoRico/8/34 and analyzed for lung pathology and immune function. Although fish oil-fed mice had lower lung inflammation compared with controls, fish oil feeding also resulted in a 40% higher mortality rate, a 70% higher lung viral load at d 7 post infection, and a prolonged recovery period following infection. Although splenic natural killer (NK) cell activity was suppressed in fish oil-fed mice, lung NK activity was not affected. Additionally, lungs of infected fish oil-fed mice had significantly fewer CD8 + T cells and decreased mRNA expression of macrophage inflammatory protein-1-a, tumor necrosis factor-a, and interleukin-6. These results suggest that the antiinflammatory properties of fish oil feeding can alter the immune response to influenza infection, resulting in increased morbidity and mortality. 4 Abbreviations used: FITC, fluorescein isothiocyanate; IFN, interferon; IL, interleukin; MIP-1a, macrophage inflammatory protein-1-a; NK, natural killer; PE, phycoerythrin; p.i., postinfection; TCID 50 , tissue culture infectious dose 50; TNFa, tumor necrosis factor-a. 0022-3166/08 $
Output: Fish Oil-Fed Mice Have Impaired Resistance to Influenza Infection 1,2
Introduction: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. Methods: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environmentbased or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). Results: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. Conclusions: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.
Output: Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis
, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). To characterize the specific role of swine influenza virus in PRDC presentation in Colombia, 11 farms from three major production regions in Colombia were examined in this study. Nasal swabs, bronchial lavage and lung tissue samples were obtained from animals displaying symptoms compatible with SIV. Isolation of SIV was performed in 9-day embryonated chicken eggs or Madin-Darby Canine Kidney (MDCK) cells. Positive isolates, identifi ed via the hemagglutination inhibition test, were further analyzed using PCR. Overall, 7 of the 11 farms were positive for SIV. Notably, sequencing of the gene encoding the hemagglutinin (HA) protein led to grouping of strains into circulating viruses identifi ed during the human outbreak of 2009, classifi ed as pandemic H1N1-2009. Serum samples from 198 gilts and multiparous sows between 2008 and 2009 were obtained to determine antibody presence of APP, Myh, PCV2 and PRRSV in both SIV-H1N1p-negative and -positive farms, but higher levels were recorded for SIV-H1N1p-positive farms. Odds ratio (OR) and P values revealed statistically signifi cant differences (p<0.05) in PRDC presentation in gilts and multiparous sows of farms positive for SIV-H1N1p. Our fi ndings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh.
Output: Association of swine infl uenza H1N1 pandemic virus (SIV- H1N1p) with porcine respiratory disease complex in sows from commercial pig farms in Colombia
Although Middle East respiratory syndrome coronavirus (MERS-CoV) has a recorded 5 years of circulation in 27 countries worldwide, there is no international study to assess whether there is variation in mortality by region. Neither has there been a comprehensive study detailing how the disease characteristics of MERS-CoV influence mortality in patients presenting symptoms. This study aimed to assess how region, patient and disease characteristics influence 14-and 45-day mortality in MERS patients. The author utilised publically available data on MERS-CoV. The study included 883 MERS patients reported between 5 January 2015 and 10 March 2017. Data on patient and disease characteristics were collected. The mean age at MERS-CoV diagnosis was 54.3 years: 69.1% were male, and 86.7% of the cases were reported from Saudi Arabia. About 40% of MERS patients studied were over the age of 60. The study estimated 14-and 45-day survival rates after initial onset of symptoms: 83.67% and 65.9%, respectively. Saudi Arabian MERS patients exhibited 4.1 and 5.0 times higher 14-day (adjusted hazard risk (aHR) = 4.1; 95% confidence interval (CI) 1.012-16.921) and 45-day (aHR = 5.0; 95% CI 1.856-13.581) mortality risk compared with MERS patients in the Republic of Korea or other countries. Similarly, Middle Eastern MERS patients showed 5.3 and 4.1 times higher 14-day (aHR = 5.3; 95% CI 1.070-25.902) and 45-day (aHR = 4.1; 95% CI 1.288-113.076) mortality risk compared with MERS patients in the Republic of Korea or other countries. The results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. Educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in MERS patients.
Output: Epidemiology and Infection Estimating survival rates in MERS-CoV patients 14 and 45 days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study
The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment. The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders. It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans.
Output: Report of the Federal Panel on Formaldehyde*
Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer $1:4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test-FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo-or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.
Output: Secondary Syphilis in Cali, Colombia: New Concepts in Disease Pathogenesis
It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'-and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.
Output: Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus
Introduction: A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods: An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results: The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19-3.62) times more likely than females to receive the H1N1 vaccination; the 45-54 and 55+ years old were 2.12 (95% CI 1.06-4.24) and 2.44 (95% CI 1.13-5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48-10.92).The 2 principal barriers were "fear of side effects" and "unsure of vaccine's effectiveness". Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications. Conclusion: Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.
Output: Healthcare workers and H1N1 vaccination: Does having a chronic disease make a difference?
Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDAapproved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.
Output: The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection
Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein-lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.
Output: Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome
IFN-induced protein with tetratricopeptide repeats 2 (IFIT2) plays important roles in host defense against viral infection as revealed by studies in humans and mice. However, little is known on porcine IFIT2 (pIFIT2). Here, we performed molecular cloning, expression profile, and transcriptional regulation analysis of pIFIT2. pIFIT2 gene, located on chromosome 14, is composed of two exons and have a complete coding sequence of 1407 bp. The encoded polypeptide, 468 aa in length, has three tetratricopeptide repeat motifs. pIFIT2 gene was unevenly distributed in all eleven tissues studied with the most abundance in spleen. Poly(I:C) treatment notably strongly upregulated the mRNA level and promoter activity of pIFIT2 gene. Upstream sequence of 1759 bp from the start codon which was assigned +1 here has promoter activity, and deltaEF1 acts as transcription repressor through binding to sequences at position − 1774 to − 1764. Minimal promoter region exists within nucleotide position − 162 and − 126. Two adjacent interferon-stimulated response elements (ISREs) and two nuclear factor (NF)-κB binding sites were identified within position − 310 and − 126. The ISRE elements act alone and in synergy with the one closer to start codon having more strength, so do the NF-κB binding sites. Synergistic effect was also found between the ISRE and NF-κB binding sites. Additionally, a third ISRE element was identified within position − 1661 to − 1579. These findings will contribute to clarifying the antiviral effect and underlying mechanisms of pIFIT2.
Output: Molecular identification and transcriptional regulation of porcine IFIT2 gene
Mouse hepatitis (MH) virus was grown in SR-CDF1-DBT, a mouse cell line, and purified by ammonium sulfate precipitation and by density gradient centrifugation. Extraction of RNA from purified virions with 1 % SDS and sedimentation analysis of the RNA revealed a major 50S component and two minor components. Treatment of virions with phenol/chloroform also produced the 50S component, although its yield was lower. MH virion RNA can bind to a poly(U)-fiberglass filter, indicating that MH virion RNA contains poly(A). A poly(A>like fragment was isolated by digestion with ribonuclease A [EC 3.1.4.22] and Tl [EC 3.1.4.8] and by DEAE-Sephadex column chromatography. Analysis of the fragment for base composition showed it to be an adenine-rich material. Its chain length was about 90 nucleotides, as determined by ion-exchange chromatography and gel electrophoresis.
Output: Polyadenylate in the Virion RNA of Mouse Hepatitis Virus
Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.
Output: Identification and characterisation of the CD40-ligand of Sigmodon hispidus
Diagnosis and identification of viruses is an important component of diagnostic virology laboratory. Although various modes of diagnostic methods are now available at disposal, a vast majority of the diseases across the globe remain undiagnosed. This is largely due to the overlapping undifferentiated set of symptoms across myriad set of RNA and DNA viral diseases. As such, it becomes critical to take into consideration several factors for viral diagnosis ranging from the type and quality of specimen collected, time of specimen collection, mode of transport, accuracy, specificity, sensitivity, and the type of diagnostic method used. This chapter broadly emphasizes various methods on diagnostic virology ranging from the classical methods of diagnosis to the most recently developed molecular methods of detection of virus.
Output: Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges
The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract ( polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.
Output: Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation
Infection by the human immunodeficiency virus (HIV) involves a number of important interactions with lipid components in host membranes that regulate binding, fusion, internalization, and viral assembly. Available data suggests that HIV actively modifies the sphingolipid content of cellular membranes to create focal environments that are favorable for infection. In this review, we summarize the roles that membrane lipids play in HIV infection and discuss the current status of therapeutics that attempt to modify biological membranes to inhibit HIV.
Output: Roles for Biological Membranes in Regulating Human Immunodeficiency Virus Replication and Progress in the Development of HIV Therapeutics that Target Lipid Metabolism
A total of 1,320 tracheal samples from 66 broiler flocks sent to slaughterhouses and 42 tracheal samples from 42 flocks of local chickens in the field were collected for infectious bronchitis virus (IBV) gene detection by reverse transcription polymerase chain reaction using nucleocapsid-specific primers and spike-specific primers. Prevalence in broiler flocks was 39.4% (26/66) and in local chicken flocks was 11.9% (5/42). Several IBVs similar to Japan were detected in Taiwan. One-direction neutralization revealed that the reference antisera did not offer protection against the IBVs similar to those from Japan.
Output: Detection of infectious bronchitis virus strains similar to Japan in Taiwan
It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably rank order high-scoring molecules), it can often can distinguish likely from unlikely ligands, often with hit rates above 10%. Here we summarize the improvements in libraries, target quality, and methods that have supported these advances, and the open access resources that make docking accessible. Recent docking screens for new ligands are sketched, as are the binding, crystallographic, and in vivo assays that support them. Like any technique, controls are crucial, and key experimental ones are reviewed. With such controls, docking campaigns can find ligands with new chemotypes, often revealing the new biology that may be docking's greatest impact over the next few years. * Corresponding Authors: J.J.I.: phone, 415-
Output: Docking Screens for Novel Ligands Conferring New Biology HHS Public Access STRUCTURE-BASED LIGAND DISCOVERY
A recombinant form of aminopeptidase N (molecular weight 99 kDa) from Escherichia coli was crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitating agent. The crystals belong to the hexagonal space group P3 1 21, with unit-cell parameters a = b = 120.5, c = 171.0 Å . The crystals are most likely to contain one molecule in the asymmetric unit, with a V M value of 3.62 Å 3 Da À1 . Diffraction data were collected to 2.0 Å resolution using Cu K radiation from a rotating-anode X-ray generator.
Output: Structural Biology and Crystallization Communications Crystallization and preliminary X-ray characterization of aminopeptidase N from Escherichia coli
A rapid and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay incorporating TaqMan™ probes has been developed that can distinguish among the six established rabies and rabies-related virus genotypes. TaqMan™ probes were designed and validated against 106 rabies and rabies-related virus isolates, one isolate of the Australian bat Lyssa6iruses (genotype 7), and 18 other non-rabies viruses important in the veterinary field. The N gene was used as the target for the probes as it is well conserved and has been intensively used to genotype rabies isolates. Additionally, it was found to contain regions specific to each genotype conducive to probe design. The RT-PCR assay described amplifies a portion of the nucleoprotein gene of all 107 rabies and rabies-related viruses, but none of the other viruses tested. Inclusion of TaqMan™-genotype-specific probes in the RT-PCR assay permits rapid identification of the virus present. By combining RT-PCR with TaqMan™ genotyping probes suspect rabies virus isolates can be identified in a single closed tube system that prevents potential PCR-product carry over contamination.
Output: A rapid RT-PCR method to differentiate six established genotypes of rabies and rabies-related viruses using TaqMan™ technology
A b s t r a c t 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.
Output: A Consensus Action Agenda for Achieving the National Health Information Infrastructure
The recombinant nucleocapsid protein (rNP) of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) was expressed in a baculovirus system. The purified SARS-CoV rNP was used as an antigen for detection of SARS-CoV antibodies in IgG enzyme-linked immunosorbent assay (ELISA). The ELISA was evaluated in comparison with neutralizing antibody assay and the authentic SARS-CoV antigen-based IgG ELISA. Two-hundred and seventy-six serum samples were collected from health care workers in a hospital in which a nosocomial SARS outbreak took place and used for evaluation. The SARS-CoV rNP-based IgG ELISA has 92% of sensitivity and specificity compared with the neutralizing antibody assay and 94% sensitivity and specificity compared with the authentic SARS-CoV antigen-based IgG ELISA. The results suggest that the newly developed SARS-CoV rNP-based IgG ELISA is a valuable tool for the diagnosis and seroepidemiological study of SARS. The SARS-CoV rNP-based IgG ELISA has an advantage over the conventional IgG ELISA in that the antigen can be prepared by laboratory workers without the risk of infection.
Output: Recombinant nucleocapsid protein-based IgG enzyme-linked immunosorbent assay for the serological diagnosis of SARS
According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas. This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development. Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.
Output: Tackling dengue fever: Current status and challenges
While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.
Output: Full Genomic Characterization of a Saffold Virus Isolated in Peru
This prospective longitudinal study investigated the epidemiology of enteric disease associated with infections in calves aging up to 70 days. A total of 850 fecal samples were collected from 67 calves. Seventeen isolates of Salmonella spp. were recovered from feces of 11 calves (16.4 %), and statistical analysis revealed no association between the presence of Salmonella spp. and clinical signs of diarrhea or age. Virulence factors of Escherichia coli were identified in 103 strains: eae (7), K99/STa (7), Stx1 (7), Stx1/eae (36), Stx1/Stx2/eae (2), Stx2 (43), and Stx2/eae (1). There was statistical association between diarrheic animals carrying E. coli Stx1/eae + in their feces at 2 and 4 weeks of age (P= 0.003) and E. coli Stx2 + at 5 weeks of age (P=0.03). Rotavirus was detected in 49 (5.76 %) fecal samples collected from 33 calves (49.2 %). The presence of rotavirus was correlated with diarrheic feces (P<0.0001) rather than feces with normal consistency. There was a significant relationship between age group and diarrhea (P = 0.001). Bovine coronavirus (BCoV) was detected in 93 fecal samples collected from 46 calves (68.6 %). There was an association (P<0.0001) between diarrheic animals positive for BCoV and age groups. The results demonstrate the importance of the pathogens studied in the etiology of diarrhea in calves.
Output: Longitudinal study of Salmonella spp., diarrheagenic Escherichia coli, Rotavirus, and Coronavirus isolated from healthy and diarrheic calves in a Brazilian dairy herd
Background: Influenza sentinel surveillance in Cote d'Ivoire showed that 70% of Acute Respiratory Infections (ARI) cases remained without etiology. This work aims to describe the epidemiological, clinical, and virological pattern of ARI that tested negative for influenza virus, in children under five years old. Materials and Methods: one thousand and fifty nine samples of patients presenting influenza Like Illness (ILI) or Severe Acute Respiratory Infections (SARI) symptoms were tested for other respiratory viruses using multiplex RT-PCR assays targeting 10 respiratory viruses. Results: The following pathogens were detected as follows, hRV 31,92% (98/307), hRSV 24.4% (75/329), PIV 20.5% (63/307), HCoV 229E 12,05% (37/307), hMPV 6.2% (19/307), HCoVOC43 1.0% (3/307) and EnV 1.0% (3/307). Among the 1,059 specimens analyzed, 917 (86.6%) were ILI samples and 142 (23.4%) were SARI samples. The proportion of children infected with at least one virus was 29.8% (273/917) in ILI cases and 23.9% (34/142) in SARI cases. The most prevalent viruses, responsible for ILI cases were hRV with 35.89% (98/273) and hRSV in SARI cases with 41.2% (14/34) of cases. Among the 1,059 patients, only 22 (2.1%) children presented risk factors related to the severity of influenza virus infection. Conclusion: This study showed that respiratory viruses play an important role in the etiology of ARI in children. For a better understanding of the epidemiology of ARI and improved case management, it would be interesting in this context to expand the surveillance of influenza to other respiratory viruses.
Output: DETECTION OF NON-INFLUENZA VIRUSES IN ACUTE RESPIRATORY INFECTIONS IN CHILDREN UNDER FIVE-YEAR-OLD IN COTE D'IVOIRE (JANUARY -DECEMBER 2013)
Background: Rapid and accurate laboratory diagnoses of viral infections are crucial for the management and treatment of patients with viral infections. Conventional methods for virus detection are labourious, time consuming, and only a single virus can be analysed in one assay. Objectives: The objective of this study was to develop a novel real-time PCR method for multiple virus detection by melting curve analysis using Taqman probes in a single reaction. Study design: As a model, six respiratory viruses were detected in one tube using three fluorophores. The specificity was assessed by cross-reaction tests with other common respiratory pathogens. The analytical sensitivity was assessed by testing the limit of detection of the assay using artificial plasmids as the positive template. The clinical evaluation of the established assay was evaluated for the detection of respiratory viruses in clinical samples, and the results were compared with direct fluorescent antibody testing (DFA). Results: The six respiratory viruses were clearly distinguished by their respective melting temperature values in the corresponding fluorescence detection channels. No cross reactions were observed by cross reaction tests. The detection limits of this assay were 2 to 2 × 10 3 copies per reaction for each virus. The clinical evaluation of this assay was demonstrated by analysing 352 clinical samples, and 67(19.0%) samples were positive for at least one virus. The accordance rate between the established PCR and DFA testing was high, and ranged from 94.57% to 100%. Conclusions: Taqman probe-based melting curve analysis is well suited for detection of multiple viruses in clinical and research laboratories because of its high throughput, reliability, and cost savings.
Output: A novel multiplex PCR for virus detection by melting curve analysis
Feline infectious peritonitis (FIP) is a fatal disease in domestic and nondomestic felids caused by feline coronavirus (FCoV). Currently, no effective vaccine is available for the prevention of this disease. In searching for agents that may prove clinically effective against FCoV infection, 16 compounds were screened for their antiviral activity against a local FCoV strain in Felis catus whole fetus-4 cells. The results showed that Galanthus nivalis agglutinin (GNA) and nelfinavir effectively inhibited FCoV replication. When the amount of virus preinoculated into the test cells was increased to mimic the high viral load present in the target cells of FIP cats, GNA and nelfinavir by themselves lost their inhibitory effect. However, when the two agents were added together to FCoV-infected cells, a synergistic antiviral effect defined by complete blockage of viral replication was observed. These results suggest that the combined use of GNA and nelfinavir has therapeutic potential in the prophylaxis and treatment of cats with early-diagnosed FIP.
Output: Synergistic antiviral effect of Galanthus nivalis agglutinin and nelfinavir against feline coronavirus
We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane ͑PDMS͒ and silver/carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing/analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography.
Output: Design and integration of an all-in-one biomicrofluidic chip
Cognitive dysfunction syndrome (CDS) is a diagnosis of exclusion given that there is no specific diagnostic test or tool and that medical disorders can cause the same set of signs. The veterinary surgeon must first identify that signs are present, collect a full history and then perform a full physical examination and relevant diagnostic tests to rule out medical causes for the signs including blood and urine analysis, radiographs and diagnostic imaging such as magnetic resonance imaging (MRI) where indicated. It is important to remember that with increasing age, there will be further degenerative changes leading to new behavioural signs that must be differentiated from CDS (Landsberg and Denenberg 2009). Only after these medical changes are detected, treated and controlled can the veterinary surgeon determine which of the signs might be caused by CDS. On the other hand, in the senior pet, medical problems and CDS can be present concurrently. In this chapter we provide the veterinary surgeon with a list of possible differential diagnoses for CDS including behavioural, medical and neurological abnormalities. In addition, we aim to provide the reader with an explanation as to how they might confound or complicate the diagnosis.
Output: 2 Behavioural and Medical Differentials of Cognitive Decline and Dementia in Dogs and Cats 2.1 Differential Diagnosis of CDS 2.1.1 Behavioural Differentials of CDS in Dogs and Cats
Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses.
Output: Virus interactions with human signal transduction pathways NIH Public Access