niryuu/sni-each-converted huggingface dataset:
Single particle tracking (SPT) of individual virion fusion with host cell membranes using total internal refl ection microscopy (TIRFM) is a powerful technique for quantitatively characterizing virus-host interactions. One signifi cant limitation of this assay to its wider use across many types of enveloped viruses, such as coronavirus, has been incorporating non-lipid receptors (proteins) into the supported lipid bilayers (SLBs) used to monitor membrane fusion. Here, we describe a method for incorporating a proteinaceous viral receptor, feline aminopeptidase N (fAPN), into SLBs using cell blebbing of mammalian cells expressing fAPN in the plasma membrane. This receptor binds feline coronavirus (FECV 1683). We describe how to carry out single particle tracking of FECV fusion in this SLB platform to obtain fusion kinetics.
Output: Chapter 16 Single Particle Tracking Assay to Study Coronavirus Membrane Fusion
Background-Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection (ARTI) in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. Methods-We conducted a prospective study March 16, 2010-March 31, 2013 using quantitative RT-PCR to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. Results-HMPV was present in 273/3168 (8.6%) of children presenting with ARTI. HMPV A2, B1, and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection (LRTI) had higher rates of cough and shortness of breath than children with LRTI infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV co-infection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. Conclusions-HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full-term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences.
Output: Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease
Ca 2+ is one of the most universal and versatile signaling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca 2+ signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca 2+ homeostasis and utilize Ca 2+ and cellular Ca 2+ -binding proteins to their benefit in their replication cycles. Ca 2+ plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear "EF-hand" Ca 2+ -binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca 2+ -binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca 2+ interactions had not been formerly appreciated. The presence of linear Ca 2+ -binding motifs in viral proteins enlarges the spectrum of Ca 2+ -virus interplay and expands the total scenario of viral calciomics. (J.J. Yang). for structural integrity or functionality; and (3) critical virus-host interactions depend on cellular Ca 2+ -regulated proteins or pathways. This review, which aims to stimulate future studies on the roles of Ca 2+ in virus infection, is focused on such interplay by highlighting recent discoveries in the biological roles of Ca 2+ in virus infection. 0143-4160/$ -see front matter
Output: Viral calciomics: Interplays between Ca 2+ and virus
In 2004, in the United States, there were 72 million presentations with a primary diagnosis of a digestive disease and 104 million presentations with combined gastrointestinal (GI) tract diseases and other diseases ( Table 1) . 1 It was also found that those who are older tend to have more GI problems, there was no difference in the rates of digestive disease between the African Americans and the whites, and women were 20% more likely to present than men with digestive diseases. Thus, more than one-third (35%) of all presentations are for digestive diseases. In 2009, in the United States, the cancer statistics revealed 275,720 new cases of GI cancer, with colorectal and pancreatic cancer in the top 10 for both men and women. 2 There were 135,830 deaths due to GI cancer, with colorectal, pancreatic, hepatic, and esophageal cancers in the top 10 for both men and women, except for esophageal cancer, which was only listed for men (Fig. 1) . 2 Furthermore, 2 of these 3 cancers that have an increasing mortality were GI tract cancers for both genders, with esophageal and hepatic cancers among men and pancreatic and hepatic cancers among women. Worldwide the rates of digestive diseases are staggering. From 1979 to 1989, in the United States, a decrease was observed in the ambulatory care visits and hospital discharges for digestive diseases. These rates remained constant between 1990 and 1999, until 2000 when the rates climbed dramatically and was still increasing in 2004 (Fig. 2) . 1 During this period, substantial increases in the
Output: Future Perspectives on Infections Associated with Gastrointestinal Tract Diseases
Avian infectious bronchitis virus (IBV), a coronavirus, causes infectious bronchitis leading to enormous economic loss in the poultry industry worldwide. Hypericin (HY) is an excellent compound that has been investigated in antiviral, antineoplastic, and antidepressant. To investigate the inhibition effect of HY on IBV infection in chicken embryo kidney (CEK) cells, 3 different experimental designs: pre-treatment of cells prior to IBV infection, direct treatment of IBV-infected cells, and pre-treatment of IBV prior to cell infection were used. Quantitative real-time PCR (qRT-PCR), immunofluorescence assay (IFA), flow cytometry, and fluorescence microscopy were performed and virus titer was determined by TCID 50 . The re-sults revealed that HY had a good anti-IBV effect when HY directly treated the IBV-infected cells, and virus infectivity decreased in a dose-dependent manner. Furthermore, HY inhibited IBV-induced apoptosis in CEK cells, and significantly reduced the mRNA expression levels of Fas, FasL, JNK, Bax, Caspase 3, and Caspase 8, and significantly increased Bcl-2 mRNA expression level in CEK cells. In addition, HY treatment could decrease IBV-induced reactive oxygen species (ROS) generation in CEK cells. These results suggested that HY showed potential antiviral activities against IBV infection involving the inhibition of apoptosis and ROS generation in CEK cells.
Output: Protective effects of hypericin against infectious bronchitis virus induced apoptosis and reactive oxygen species in chicken embryo kidney cells
Pseudorabies virus (PRV), an alphaherpesvirus closely related to Varicella-Zoster virus (VZV) and Herpes simplex type 1 (HSV1) infects mucosa epithelia and the peripheral nervous system (PNS) of its host. We previously demonstrated that PRV infection induces a specific and lethal inflammatory response, contributing to severe neuropathy in mice. So far, the mechanisms that initiate this neuroinflammation remain unknown. Using a mouse footpad inoculation model, we found that PRV infection rapidly and simultaneously induces high G-CSF and IL-6 levels in several mouse tissues, including the footpad, PNS and central nervous system (CNS) tissues. Interestingly, this global increase occurred before PRV had replicated in dorsal root ganglia (DRGs) neurons and also was independent of systemic inflammation. These high G-CSF and IL-6 levels were not caused by neutrophil infiltration in PRV infected tissues, as we did not detect any neutrophils. Efficient PRV replication and spread in the footpad was sufficient to activate DRGs to produce cytokines. Finally, by using knockout mice, we demonstrated that TLR2 and IFN type I play crucial roles in modulating the early neuroinflammatory response and clinical outcome of PRV infection in mice. Overall, these results give new insights into the initiation of virus-induced neuroinflammation during herpesvirus infections. Herpesviruses are major pathogens worldwide. Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). The natural host is the pig, but PRV can infect most mammals. In these non-natural hosts, the virus causes a severe pruritus called the 'mad itch'. Interestingly, PRV infects the peripheral nervous system (PNS) and induces a specific and lethal inflammatory response in mice, yet little is know about how this neuroinflammatory response is initiated. In this study, we demonstrated for the first time how PNS neurons tightly regulate the inflammatory response during PRV infection and contribute to severe clinical outcome in mice. Our work provides new insights into the process of alphaherpesvirus-induced neuropathies, leading to the development of innovative therapeutic strategies.
Output: Alphaherpesvirus infection of mice primes PNS neurons to an inflammatory state regulated by TLR2 and type I IFN signaling
Background: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value). We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews. We identified 57 primary studies and 49 systematic reviews. Fifty-six percent of primary studies and 53% of systematic reviews used graphical displays to present results. Dot-plot or boxand-whisker plots were the most commonly used graph in primary studies and were included in 22 (39%) studies. ROC plots were the most common type of plot included in systematic reviews and were included in 22 (45%) reviews. One primary study and five systematic reviews included a probability-modifying plot. Graphical displays are currently underused in primary diagnostic accuracy studies and systematic reviews of such studies. Diagnostic accuracy studies need to include multiple types of graphic in order to provide both a detailed overview of the results (diagnostic accuracy) and to communicate information that can be used to inform clinical practice (predictive value). Work is required to improve graphical displays, to better communicate the utility of a test in clinical practice and the implications of test results for individual patients.
Output: Graphical presentation of diagnostic information
Objective: Effective pandemic responses rely on frontline healthcare workers continuing to work despite increased risk to themselves. Our objective was to investigate Alberta family physicians willingness to work during an influenza pandemic. Design: Cross-sectional survey. Setting: Alberta prior to the fall wave of the H1N1 epidemic. Participants: 192 participants from a random sample of 1000 Alberta family physicians stratified by region. Main Outcome Measures: Willingness to work through difficult scenarios created by an influenza epidemic. Results: The corrected response rate was 22%. The most physicians who responded were willing to continue working through some scenarios caused by a pandemic, but in other circumstances less than 50% would continue. Men were more willing to continue working than women. In some situations South African and British trained physicians were more willing to continue working than other groups. Conclusions: Although many physicians intend to maintain their practices in the event of a pandemic, in some circumstances fewer are willing to work. Pandemic preparation requires ensuring a workforce is available. Healthcare systems must provide frontline healthcare workers with the support and resources they need to enable them to continue providing care.
Output: Alberta family physicians' willingness to work during an influenza pandemic: a cross-sectional study
Bats in the EU have been associated with several zoonotic viral pathogens of significance to both human and animal health. Virus discovery continues to expand the existing understating of virus classification, and the increased interest in bats globally as reservoirs or carriers of zoonotic agents has fuelled the continued detection and characterisation of new lyssaviruses and other viral zoonoses. Although the transmission of lyssaviruses from bat species to humans or terrestrial species appears rare, interest in these viruses remains, through their ability to cause the invariably fatal encephalitis-rabies. The association of bats with other viral zoonoses is also of great interest. Much of the EU is free of terrestrial rabies, but several bat species harbor lyssaviruses that remain a risk to human and animal health. Whilst the rabies virus is the main cause of rabies globally, novel related viruses continue to be discovered, predominantly in bat populations, that are of interest purely through their classification within the lyssavirus genus alongside the rabies virus. Although the rabies virus is principally transmitted from the bite of infected dogs, these related lyssaviruses are primarily transmitted to humans and terrestrial carnivores by bats. Even though reports of zoonotic viruses from bats within the EU are rare, to protect human and animal health, it is important characterise novel bat viruses for several reasons, namely: (i) to investigate the mechanisms for the maintenance, potential routes of transmission, and resulting clinical signs, if any, in their natural hosts; (ii) to investigate the ability of existing vaccines, where available, to protect against these viruses; (iii) to evaluate the potential for spill over and onward transmission of viral pathogens in novel terrestrial hosts. This review is an update on the current situation regarding zoonotic virus discovery within bats in the EU, and provides details of potential future mechanisms to control the threat from these deadly pathogens.
Output: Tropical Medicine and Infectious Disease Bats and Viruses: Emergence of Novel Lyssaviruses and Association of Bats with Viral Zoonoses in the EU
Background: The traditional Serfling-type approach for influenza-like illness surveillance requires long historical time-series. We retrospectively evaluated the use of recent, short, historical time-series for recognizing the onset of community outbreaks of respiratory tract infections (RTIs). The data used referred to the proportion of diagnoses for upper or lower RTIs to total diagnoses for house-call visits, performed by a private network of medical specialists (SOS Doctors) in the metropolitan area of Athens, Greece, between January 01, 2000 and October 12, 2008. The reference standard classification of the observations was obtained by generating epidemic thresholds after analyzing the full 9-year period. We evaluated two different alert generating methods [simple regression and cumulative sum (CUSUM), respectively], under a range of input parameters, using data for the previous running 4-6 week period. These methods were applied if the previous weeks contained non-aberrant observations. Results: We found that the CUSUM model with a specific set of parameters performed marginally better than simple regression for both groups. The best results (sensitivity, specificity) for simple regression and CUSUM models for upper RTIs were (1.00, 0.82) and (0.94, 0.93) respectively. Corresponding results for lower RTIs were (1.00, 0.80) and (0.93, 0.91) respectively. Conclusions: Short-term data for house-call visits can be used rather reliably to identify respiratory tract outbreaks in the community using simple regression and CUSUM methods. Such surveillance models could be particularly useful when a large historical database is either unavailable or inaccurate and, thus, traditional methods are not optimal.
Output: Surveillance of Community Outbreaks of Respiratory Tract Infections Based on House-Call Visits in the Metropolitan Area of Athens, Greece
Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ,2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (,80%) movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for careful consideration of human social interactions when designing infectious disease mitigation strategies, particularly within resource-poor urban environments. Citation: Vazquez-Prokopec GM, Bisanzio D, Stoddard ST, Paz-Soldan V, Morrison AC, et al. (2013) Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment. PLoS ONE 8(4): e58802.
Output: Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment
Background: Anvillea garcinii Coss. & Durieu (Anv) plant is used as a traditional North African medicine against several diseases associated with inflammation. At inflammatory sites, reactive oxygen species (ROS) produced in excess by activated phagocyte NADPH oxidase (NOX2) can accentuate inflammatory responses. Thus, we investigated if Anv-water soluble polysaccharides could modulate primary human neutrophil oxidative burst in vitro. Methods: Human neutrophils were isolated from fresh whole blood and O 2 .generation was measured by cytochrome c reduction assays. Western blots were used to analyse the translocation of PKC, p47 phox (a key component of NOX2 activity) to neutrophil plasma membrane. Also, myeloperoxidase (MPO) release in the extracellular medium was studied by western blots. Flow cytometric analysis was used to detect CD11b membrane expression. Results: Water soluble polysaccharides from Anv dose-dependently inhibited N-formyl-methionyl-leucylphenylalanine (fMLF)-and phorbol myristate acetate (PMA)-induced O 2 .generation by human neutrophils. Moreover, Anv-polysaccharides strongly inhibited PMA-induced PKCβ and p47 phox translocation to membranes and p47 phox phosphorylation on Ser328, a main PKC target. In contrast, polysaccharides extract from Zygophyllum gaetulum plant, which is also used as a traditional North African medicine against inflammatory diseases, was ineffective on this PKCβ-p47phox pathway. Further, Anv inhibited important neutrophil degranulation markers corresponding to myeloperoxidase (MPO) release and CD11b membrane expression. Conclusion: The process of down-regulating NADPH oxidase by polysaccharides extracts from Anv provides new insights into the mechanism of Anv's anti-inflammatory actions.
Output: Anvillea garcinii extract inhibits the oxidative burst of primary human neutrophils
The family of natriuretic peptides (NPs), including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), exert important and diverse actions for cardiovascular and renal homeostasis. The autocrine and paracrine functions of the NPs are primarily mediated through the cellular membrane bound guanylyl cyclase-linked receptors GC-A (NPR-A) and GC-B (NPR-B). As the ligands and receptors each contain disulfide bonds, a regulatory role for the cell surface protein disulfide isomerase (PDI) was investigated. Objective: We utilized complementary in vitro and in vivo models to determine the potential role of PDI in regulating the ability of the NPs to generate its second messenger, cyclic guanosine monophosphate. Methods and Results: Inhibition of PDI attenuated the ability of ANP, BNP and CNP to generate cGMP in human mesangial cells (HMCs), human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs), each of which were shown to express PDI. In LLC-PK1 cells, where PDI expression was undetectable by immunoblotting, PDI inhibition had a minimal effect on cGMP generation. Addition of PDI to cultured LLC-PK1 cells increased intracellular cGMP generation mediated by ANP. Inhibition of PDI in vivo attenuated NP-mediated generation of cGMP by ANP. Surface Plasmon Resonance demonstrated modest and differential binding of the natriuretic peptides with immobilized PDI in a cell free system. However, PDI was shown to co-localize on the surface of cells with GC-A and GC-B by co-immunoprecpitation and immunohistochemistry. Conclusion: These data demonstrate for the first time that cell surface PDI expression and function regulate the capacity of natriuretic peptides to generate cGMP through interaction with their receptors.
Output: Cell Surface Protein Disulfide Isomerase Regulates Natriuretic Peptide Generation of Cyclic Guanosine Monophosphate
Hospitals develop nurse schedules that cover a period of 4-6 weeks and are posted several weeks in advance. Once posted, changes to the schedule require voluntary participation by the nurses, making it difficult for hospitals to respond to changes in nursing needs and availability of nurses. At the same time, nursing needs' forecasts developed several weeks in advance are often wrong. In each hospital setting, there may exist several promising strategies to enhance scheduling flexibility and reduce the mismatch between the nursing needs and the availability of nurses. However, methodologies to evaluate such strategies, before testing them in expensive pilot implementation, do not exist. We demonstrate how such evaluations can be carried out using historical data. Furthermore, we demonstrate the use of our approach by evaluating the benefits of a strategy where nurses are divided into two cohorts and schedules are phase shifted for the two cohorts. Staggering schedules allows nursing unit managers to benefit from more frequent updating of needs' assessments without having to change work rules. Upon applying our approach to data from a large urban hospital, we discovered that in this example staggering did not improve the performance of nurse schedules. We discuss possible reasons for this result, its implications for hospital managers, and other potential uses of our approach.
Output: On evaluating the impact of flexibility enhancing strategies on the performance of nurse schedules
Insensitivity and technical complexity have impeded the implementation of high-throughput nucleic acid sequencing in differential diagnosis of viral infections in clinical laboratories. Here, we describe the development of a virome capture sequencing platform for vertebrate viruses (VirCapSeq-VERT) that increases the sensitivity of sequence-based virus detection and characterization. The system uses~2 million probes that cover the genomes of members of the 207 viral taxa known to infect vertebrates, including humans. A biotinylated oligonucleotide library was synthesized on the NimbleGen cleavable array platform and used for solution-based capture of viral nucleic acids present in complex samples containing variable proportions of viral and host nucleic acids. The use of VirCapSeq-VERT resulted in a 100-to 10,000-fold increase in viral reads from blood and tissue homogenates compared to conventional Illumina sequencing using established virus enrichment procedures, including filtration, nuclease treatments, and RiboZero rRNA subtraction. VirCapSeq-VERT had a limit of detection comparable to that of agent-specific real-time PCR in serum, blood, and tissue extracts. Furthermore, the method identified novel viruses whose genomes were approximately 40% different from the known virus genomes used for designing the probe library. The VirCapSeq-VERT platform is ideally suited for analyses of virome composition and dynamics. IMPORTANCE VirCapSeq-VERT enables detection of viral sequences in complex sample backgrounds, including those found in clinical specimens, such as serum, blood, and tissue. The highly multiplexed nature of the system allows both the simultaneous identification and the comprehensive genetic characterization of all known vertebrate viruses, their genetic variants, and novel viruses. The operational simplicity and efficiency of the VirCapSeq-VERT platform may facilitate transition of high-throughput sequencing to clinical diagnostic as well as research applications. Citation Briese T, Kapoor A, Mishra N, Jain K, Kumar A, Jabado OJ, Lipkin WI. 2015. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. mBio 6(5):e01491-15.
Output: Virome Capture Sequencing Enables Sensitive Viral Diagnosis and Comprehensive Virome Analysis
Objective: To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. , were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results: Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P¼.04) and allcause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups. Conclusion: Dipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.
Output: Patients and Methods: Data from the National Health Insurance Research Database from
Background-Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. Methods-We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. Results-There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). Conclusions-Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset. Long-term care; Pediatrics; Outbreaks; Acute respiratory infection Hand hygiene is the primary recommendation for preventing infections in health care settings. 1 A recent review identified several studies conducted in acute care which have
Output: Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care?
Research on respiratory protection against biologic agents is important to address major concerns such as occupational safety and terrorist attack. This review describes the literature on respiratory protection against bioaerosols and identifies research gaps. Respiratory protection is a complex field involving a number of factors, such as the efficiency of respirator filter material; facepiece fitting; and maintenance, storage, and reuse of respirators. Several studies used nonpathogenic microorganisms having physical characteristics similar to that of Mycobacterium tuberculosis to analyze microbial penetration through respirators. Some studies showed that high-efficiency particulate air (HEPA) and N95 filters provided a higher level of protection than dust/mist (DM) and dust/mist/fume (DMF) filters. Flow rate and relative humidity appear to alter the level of penetration of microorganisms through respirator filters. The relationship between microbial penetration through respirator filters and the aerodynamic diameter, length, or other physical characteristics of microorganisms remains controversial. Whether reaerosolization of bioaerosol particles should be a concern is unclear, given the fact that one study has demonstrated significant reaerosolization of 1-to 5-mm particles loaded onto respirator filters. Respirator maintenance, storage, and decontamination are important factors to be considered when reusing respirators. The respiratory protection against biologic warfare agents such as anthrax in military and civilian situations is described. (Am J Infect Control 2004;32:345-54.) 
Output: Respiratory protection against bioaerosols: Literature review and research needs
In northeastern Thai (Isaan) culture traditional raw fish dishes and raw fish-eating habits are common. Eating and sharing meals together among the community's members, especially relatives and neighbours, are a common practice in both daily life and social gathering events. Fish are a significant protein source and are associated with variety of traditional recipes. Cyprinid fish are one of the most preferred fish by Isaan villagers for daily consumption because they are accessible and affordable. Consumption of these fish probably causes the persistence of high endemicity of human liver fluke infection, particularly with Opisthorchis viverrini, in northeast Thailand. Because the consumption of raw cyprinid fish is a well-documented risk factor for liver fluke infection, sharing of risky raw fish dishes may influence disease transmission through a community. Social network analysis was used to investigate fish and fish-based meal sharing among household members in Isaan villages in liver fluke endemic areas. The findings from three studies confirmed the persistence of traditional Isaan raw fish consumption and food-sharing practice. Social connections via food sharing among villagers played an important role in liver fluke infection and transmission dynamics as a risk factor. Thus these sociocultural factors should be taken into account in designing strategies for control of opisthorchiasis and other food-borne illnesses at the community level.
Output: Social Influence in Liver Fluke Transmission: Application of Social Network Analysis of Food Sharing in Thai Isaan Culture
There is a continuing threat that the highly pathogenic avian influenza virus will cause future influenza pandemics. In this study, we screened a library of compounds that are biologically active and structurally diverse for inhibitory activity against influenza neuraminidase (NA). We found that aurintricarboxylic acid (ATA) is a potent inhibitor of NA activity of both group-1 and group-2 influenza viruses with IC 50 s (effective concentration to inhibit NA activity by 50%) values at low micromolar concentrations. ATA was equally potent in inhibiting the NA activity derived from wild-type NA and its H274Y mutant which renders NA resistance to inhibition by oseltamivir. Although ATA is structurally distinct from sialic acid, molecular modeling experiments suggested that ATA binds to NA at the enzyme's substrate binding site. These results indicate that ATA may be a good starting material for the design of a novel class of NA inhibitors for the treatment influenza viruses.
Output: Aurintricarboxylic acid inhibits influenza virus neuraminidase
Over the last three decades, virus-like particles (VLPs) have evolved to become a widely accepted technology, especially in the field of vaccinology. In fact, some VLP-based vaccines are currently used as commercial medical products, and other VLP-based products are at different stages of clinical study. Several remarkable advantages have been achieved in the development of VLPs as gene therapy tools and new nanomaterials. The analysis of published data reveals that at least 110 VLPs have been constructed from viruses belonging to 35 different families. This review therefore discusses the main principles in the cloning of viral structural genes, the relevant host systems and the purification procedures that have been developed. In addition, the methods that are used to characterize the structural integrity, stability, and components, including the encapsidated nucleic acids, of newly synthesized VLPs are analyzed. Moreover, some of the modifications that are required to construct VLP-based carriers of viral origin with defined properties are discussed, and examples are provided.
Output: Construction and Characterization of Virus-Like Particles: A Review
Archive central nervous tissue from 286 cats with neurological disorders was reviewed for histological evidence of feline spongiform encephalopathy (FSE), which may have occurred before it was first recognized in 1990. The following six categories of disease were identified: congenital; degenerative; inflammatory; neoplastic; FSE; lesion-free. The largest category (inflammatory) contained 92 cats, of which 47 were considered to be consistent with infection by feline infectious peritonitis (FIP) virus. Six cats showed evidence of more than one disease process; thus, one cat with FIP also had toxocara infection of the lateral ventricles and five cats with FSE also showed perivascular cuffing suggestive of concurrent viral infection. In only two cases did the diagnosis on review differ significantly from the original interpretation. There was no evidence of FSE before the original case was recognized in April 1990. q
Output: A Retrospective Study of 286 Cases of Neurological Disorders of the Cat
Using fusions between the Escherichia coli genes argI and lacZ, it has been demonstrated that ribosomal frameshifting occurs at a frequency of between 3% and 16% within the argI mRNA, soon after the initiation codon. The frameshift involves a phenylalanyl-tRNA shifting into the + 1 frame at the sequence UUU-U/C. The shift does not occur if the in-frame phenylalanine codon UUU is replaced by UUC. The level of frameshifting is higher in dense cultures and is not dependent on phenylalanine starvation. In the wild-type argI gene this frameshifting event would be an error, leading to a truncated, non-functional protein. Therefore, it is unlike the numerous examples of required frameshifting events that have been described in other genes.
Output: A ribosomal frameshifting error during translation of the argl mRNA of Escherichia coil
The calcium-sensing receptor (CaR) regulates transepithelial calcium transport into milk by mammary epithelial cells. Using a genome-wide screening strategy, we identified the plasma membrane calcium ATPase isoform 2 (PMCA2) as a potential downstream target of the CaR. We show that PMCA2 expression in the mouse mammary gland increases during lactation and that PMCA2 is localized solely to the apical plasma membrane of mammary epithelial cells. In milk from deafwaddler mice, which have mutations in the gene encoding PMCA2, calcium concentrations were reduced, confirming its importance in calcium transport into milk. Furthermore, in cultured primary and EpH4 mouse mammary epithelial cells, CaR stimulation up-regulated calcium-dependent ATPase ac-tivity in plasma membrane preparations. By small interfering RNA-mediated gene knockdown of PMCA2, we show that PMCA2 accounts for the preponderance of calcium-ATPase activity. We also show that reduction of CaR expression with small interfering RNA eliminates the ability of extracellular calcium to elicit an increase in calcium-dependent ATPase activity in EpH4 cell membranes. These results demonstrate that activation of the CaR increases PMCA2 activity in mouse mammary epithelial cells, providing a mechanism for the regulation of transepithelial calcium transport by calcium in the lactating mouse mammary gland. (Endocrinology 148: 5943-5954, 2007)
Output: The Calcium-Sensing Receptor Regulates Plasma Membrane Calcium Adenosine Triphosphatase Isoform 2 Activity in Mammary Epithelial Cells: A Mechanism for Calcium-Regulated Calcium Transport into Milk
In vitro, nitric oxide (NO) has been shown to have antimicrobial activity against a wide range of viruses, including influenza A virus. Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. NO was delivered to influenza-infected mice either continuously or intermittently at 80 or 160 ppm, respectively, using both prophylactic and post-infection treatment strategies. Murine survival and weight loss were assessed, and lung viral load was quantified via plaque assay. Here, we report that iNO administered prophylactically or post-influenza infection failed to improve survival of infected mice. No difference in lung viral load was observed between experimental groups. Although NO has antiviral activity against influenza A virus in vitro, iNO therapy provided no apparent benefit when used for treatment of influenza A virus infection in vivo.
Output: Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza
Background: The detrimental role of viruses has been well described in CF, although the pattern of virus infections has not been investigated in a longitudinal study. The primary aim was to determine the feasibility of fortnightly parent collected swabs in young children with CF. Methods: Children under three years with CF were recruited. Nasal swabs were collected by parents every fortnight and during periods of symptoms over 12 months. Nasal swabs were posted and virus detected using real-time PCR. Results: Only 27% of the patients completed the study to 10 months, although 98% of the swabs returned were adequate for analysis. Mould was observed growing on 23% of the returned swabs. There was no evidence to demonstrate relationships with symptoms and viruses, prolonged symptoms, prolonged shedding or patterns of virus infections. Conclusions: This study highlights the need to further investigate the role of viruses in children with CF using a robust method of frequent collection in children for a longitudinal study, with appropriate storage and shipping techniques to avoid mould growth or other potential contaminants.
Output: Original Article
Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN-or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage's LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC-SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1 + or DC-SIGN + macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1 + macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.
Output: Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae
Porcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus in pigs. We have isolated and passaged the PDCoV strain OH-FD22 in an LLC porcine kidney (LLC-PK) cell line. Our study investigated the pathogenicity of the tissue-culture-grown PDCoV (TC-PDCoV) OH-FD22 at cell passages 5, 20 and 40 in LLC-PK cells, in eight 14-day-old gnotobiotic (Gn) pigs. Pigs (n = 3) were euthanized for pathologic examination at post-inoculation day (PID) 3, and the remainder were monitored for clinical signs, virus shedding, and serum antibody responses until PID 28. All inoculated pigs developed watery diarrhea and/or vomiting at PID 1-2 and shed the highest amount of viral RNA in feces at PID 3-5, accompanied by severe atrophic enteritis. They developed high titers of PDCoV-specific IgG/IgA and virus-neutralizing antibodies in serum at PID 23-24. Histologic lesions were limited to the villous epithelium of the jejunum and ileum at PID 3. Two inoculated pigs tested at PID 23-24 had small to moderate numbers of PDCoV antigen-positive cells in the intestinal lamina propria and mesenteric lymph nodes, but not in enterocytes. An analysis of full-length S and N genes of TC-and Gn-pig-passaged OH-FD22 revealed a high genetic stability in cell culture and pigs. TC-PDCoV OH-FD22 (cell passages 5, 20 and 40) was enteropathogenic, and the pathogenicity was similar to that of the original field virus. The TC-PDCoV OH-FD22 will be useful for further pathogenesis studies and for evaluating if higher-level cell-culture passaged virus becomes attenuated for vaccine development.
Output: Experimental infection of gnotobiotic pigs with the cell-culture-adapted porcine deltacoronavirus strain OH-FD22
Background. The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. Methods. Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. Results. Among 15 942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2-11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%-66% reduced risk of hospitalization. Among adolescents aged 12-20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. Conclusions. Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options.
Output: Clinical Infectious Diseases
KEYWORDS Posttransplant infections Posttransplant ICU care Solid organ transplantation Risk factors Solid organ transplant (SOT) has become a well-established standard of care for endorgan failure. The nurse in the intensive care unit may be exposed to these patients at any stage in the care continuum of pretransplant or posttransplant care. Factors affecting the incidence of infection after SOT include the type of organ transplanted, anatomic region of transplant, incidence of surgical complications, level of immunosuppression, and antirejection therapy. Knowledge of risk factors, timing, and treatments for infections may help to enhance clinical practices and optimize patient safety and clinical outcomes. Crit Care Nurs Clin N Am 29 (2017) 97-110 http://dx.
Output: Infections in the Intensive Care Unit Posttransplant Infections