bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Health‐related quality of life in pediatric patients with cystic fibrosis
Authors: Patrick Jonathan R. D. , da Fonseca Marcio A. , Kaste Linda M. , Fadavi Shahrbanoo , Shah Neal , Sroussi Hervé 
Published: January 2016

ABSTRACTPurposeTo compare the oral health‐related quality of life (OHRQoL) of 8‐ to 12‐year‐old children and 13‐ to 17‐year‐old adolescents diagnosed with cystic fibrosis (CF).Materials and methodsParticipants were recruited from a Midwest CF center. Parents provided demographic information and their assessment of the child's health. Patients completed the Child Oral Health Impact Profile (COHIP).ResultsThirty‐nine child‐parent pairs participated. Fifty four percent of the patients were male, 87% Caucasian, and 56% adolescent, with 66% of families reporting an annual income of over $100,000. Excellent or very good health, including oral health, was reported by 67% of the patients. Individuals taking 10 or more medications reported better OHRQoL while Caucasians reported better oral health and total scores than other races. Adolescents had poorer total COHIP, social‐emotional well‐being, and self‐image scores.ConclusionAlthough most patients reported good or excellent oral health, adolescents reported a poorer OHRQoL than younger patients.
The tyrosine kinase inhibitor toceranib in feline injection site sarcoma: efficacy and side effects
Authors: Holtermann N. , Kiupel M. , Hirschberger J. 
Published: January 2016

AbstractBecause of their locally invasive growth and high recurrence rate despite of aggressive local therapy, treatment of feline sarcomas is challenging. The tyrosine kinase inhibitor (TKI) toceranib is currently licensed for the treatment of canine mast cell tumours. There are only few reports aboutTKIusage in cats. Previous studies indicated promising potential ofTKIfor the treatment of feline injection site sarcoma (FISS). In this prospective clinical trial, 18 cats with unresectableFISSwere treated at a target dosage of 3.25 mg kg−1every other day to evaluate the clinical efficacy and toxicity of toceranib. There was no clinical response measurable. Adverse events were generally mild and temporary. Grade 3 or 4 adverse events developed infrequently and all resolved with drug holidays and dose reductions.
Enhancing Adoption of a Home-Based Exercise Program for Mild Balance Dysfunction: A Qualitative Study
Authors: Meyer Claudia , Williams Susan , Batchelor Frances , Hill Keith 
Published: January 2016

Introduction:The aim was to identify barriers and opportunities facing community health physiotherapists in delivering a home-based balance exercise program to address mild balance dysfunction and, secondly, to understand the perspectives of older people in adopting this program.Method:Focus groups, written surveys, and data recording sheets were used with nine older people and five physiotherapists. Focus groups were audio taped, transcribed, and coded independently by two researchers.Results:Thematic content analysis was undertaken. Emerging themes were: engaging in preventive health (various benefits, enhancing independence); adoption of strategies (acceptable design and implementation feasibility); exercising in context (convenience, practicality, and safety); and broader implementation issues (program design, proactive health messages, and a solid evidence base).Conclusion:The views of older people and physiotherapists were sought to understand the adoption of a previously successful home-based program for mild balance dysfunction. Understanding the unique context and circumstances for individuals and organizations will enhance adoption.
Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial
Authors: Dunning Andrew J. , DiazGranados Carlos A. , Voloshen Timothy , Hu Branda , Landolfi Victoria A. , Talbot H. Keipp 
Published: January 2016

ABSTRACT
Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus—the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.)
Rapid Detection of Vancomycin-Intermediate Staphylococcus aureus by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Mather Cheryl A. , Werth Brian J. , Sivagnanam Shobini , SenGupta Dhruba J. , Butler-Wu Susan M. 
Published: January 2016

ABSTRACT

Vancomycin is the standard of care for the treatment of invasive methicillin-resistant
Staphylococcus aureus
(MRSA) infections. Infections with vancomycin-nonsusceptible MRSA, including vancomycin-intermediate
S. aureus
(VISA) and heterogeneous VISA (hVISA), are clinically challenging and are associated with poor patient outcomes. The identification of VISA in the clinical laboratory depends on standard susceptibility testing, which takes at least 24 h to complete after isolate subculture, whereas hVISA is not routinely detected in clinical labs. We therefore sought to determine whether VISA and hVISA can be differentiated from vancomycin-susceptible
S. aureus
(VSSA) using the spectra produced by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Strains of MRSA were characterized for vancomycin susceptibility phenotype by broth microdilution and modified population analysis. We tested 21 VISA, 21 hVISA, and 38 VSSA isolates by MALDI-TOF MS. Susceptibility phenotypes were separated by using a support vector machine (SVM) machine learning algorithm. The resulting model was validated by leave-one-out cross validation. Models were developed and validated by using spectral profiles generated under various subculture conditions, as well as with and without hVISA strains. Using SVM, we correctly identified 100% of the VISA and 97% of the VSSA isolates with an overall classification accuracy of 98%. Addition of hVISA to the model resulted in 76% hVISA identification, 100% VISA identification, and 89% VSSA identification, for an overall classification accuracy of 89%. We conclude that VISA/hVISA and VSSA isolates are separable by MALDI-TOF MS with SVM analysis.
Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis
Authors: Farhat Maha R. , Jacobson Karen R. , Franke Molly F. , Kaur Devinder , Sloutsky Alex , Mitnick Carole D. , Murray Megan 
Published: January 2016

ABSTRACT

Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the
gyr
genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of
gyr
mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full
gyrA
and
gyrB
open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that
gyrB
mutations contribute to fluoroquinolone resistance both individually and through interactions with
gyrA
mutations. These effects were statistically significant. In these clinical isolates, several
gyrA
and
gyrB
mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of
gyr
mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of
gyr
mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment.
Evaluation of a New Device for Simplifying and Standardizing Stool Sample Preparation for Viral Molecular Testing with Limited Hands-On Time
Authors: Feghoul Linda , Salmona Maud , Cherot Janine , Fahd Mony , Dalle Jean-Hugues , Vachon Carole , Perrod Aurélie , Bourgeois Philippe , Scieux Catherine , Baruchel André , Simon François , LeGoff Jérôme 
Published: January 2016

ABSTRACT

Sensitive molecular assays have greatly improved the diagnosis of viral gastroenteritis. However, the proper preparation of stool samples for clinical testing remains an issue. bioMérieux has developed a stool preprocessing device (SPD) that includes a spoon for calibrated sampling and a vial containing buffer, glass beads, and two filters. The resulting stool filtrate is used for nucleic acid extraction. The purpose of this study was to evaluate the performance of the SPD for the quantification of human adenovirus (HAdV) DNA in stool samples collected from hematopoietic stem cell transplant (HSCT) recipients. HAdV DNA was quantified with the Adenovirus R-gene kit. The suitability of the device to reproducibly quantify HAdV DNA in stools using different extraction platforms (easyMAG and QIAsymphony) was determined using archived HAdV-positive stool samples. Coefficients of variation of HAdV DNA quantifications ranged from 1.79% to 1.83%, and no difference in quantification was observed between the two extraction systems. The HAdV DNA limit of quantification using the SPD was 3.75 log
10
copies/g of stool. HAdV DNA quantification using the SPD was then compared to that of the routine preprocessing technique on 75 fresh stool samples collected prospectively from pediatric HSCT recipients at risk for HAdV infections. Thirty-eight samples were HAdV DNA positive with both the SPD and routine preprocessing methods. HAdV DNA loads were on average 1.14-log
10
copies/g of stool higher with the SPD (
P
< 0.0001) than with routine methods. This new device enabled a standardized preparation of stool samples in <5 min and a reproducible and sensitive quantification of HAdV DNA. The use of the SPD for the detection of other gastrointestinal infections warrants further evaluation.
Automated Broad-Range Molecular Detection of Bacteria in Clinical Samples
Authors: Budding Andries E. , Hoogewerf Martine , Vandenbroucke-Grauls Christina M. J. E. , Savelkoul Paul H. M. 
Published: January 2016

ABSTRACT
Molecular detection methods, such as quantitative PCR (qPCR), have found their way into clinical microbiology laboratories for the detection of an array of pathogens. Most routinely used methods, however, are directed at specific species. Thus, anything that is not explicitly searched for will be missed. This greatly limits the flexibility and universal application of these techniques. We investigated the application of a rapid universal bacterial molecular identification method, IS-pro, to routine patient samples received in a clinical microbiology laboratory. IS-pro is a eubacterial technique based on the detection and categorization of 16S-23S rRNA gene interspace regions with lengths that are specific for each microbial species. As this is an open technique, clinicians do not need to decide in advance what to look for. We compared routine culture to IS-pro using 66 samples sent in for routine bacterial diagnostic testing. The samples were obtained from patients with infections in normally sterile sites (without a resident microbiota). The results were identical in 20 (30%) samples, IS-pro detected more bacterial species than culture in 31 (47%) samples, and five of the 10 culture-negative samples were positive with IS-pro. The case histories of the five patients from whom these culture-negative/IS-pro-positive samples were obtained suggest that the IS-pro findings are highly clinically relevant. Our findings indicate that an open molecular approach, such as IS-pro, may have a high added value for clinical practice.
Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing
Authors: Hasan Mohammad R. , Rawat Arun , Tang Patrick , Jithesh Puthen V. , Thomas Eva , Tan Rusung , Tilley Peter 
Published: January 2016

ABSTRACT

Next-generation sequencing (NGS) technology has shown promise for the detection of human pathogens from clinical samples. However, one of the major obstacles to the use of NGS in diagnostic microbiology is the low ratio of pathogen DNA to human DNA in most clinical specimens. In this study, we aimed to develop a specimen-processing protocol to remove human DNA and enrich specimens for bacterial and viral DNA for shotgun metagenomic sequencing. Cerebrospinal fluid (CSF) and nasopharyngeal aspirate (NPA) specimens, spiked with control bacterial and viral pathogens, were processed using either a commercially available kit (MolYsis) or various detergents followed by DNase prior to the extraction of DNA. Relative quantities of human DNA and pathogen DNA were determined by real-time PCR. The MolYsis kit did not improve the pathogen-to-human DNA ratio, but significant reductions (>95%;
P
< 0.001) in human DNA with minimal effect on pathogen DNA were achieved in samples that were treated with 0.025% saponin, a nonionic surfactant. Specimen preprocessing significantly decreased NGS reads mapped to the human genome (
P
< 0.05) and improved the sensitivity of pathogen detection (
P
< 0.01), with a 20- to 650-fold increase in the ratio of microbial reads to human reads. Preprocessing also permitted the detection of pathogens that were undetectable in the unprocessed samples. Our results demonstrate a simple method for the reduction of background human DNA for metagenomic detection for a broad range of pathogens in clinical samples.
Detection and Prevalence of Penicillin-Susceptible Staphylococcus aureus in the United States in 2013
Authors: Richter S. S. , Doern G. V. , Heilmann K. P. , Miner S. , Tendolkar S. , Riahi F. , Diekema D. J. 
Published: January 2016

ABSTRACT

Using
blaZ
PCR as the “gold standard,” the sensitivities of CLSI penicillin zone edge and nitrocefin-based tests for β-lactamase production in
Staphylococcus aureus
were 64.5% and 35.5%, respectively, with specificity of 99.8% for both methods. In 2013, 13.5% of 3,083
S. aureus
isolates from 31 U.S. centers were penicillin susceptible.
Morphological, Biochemical, and Functional Study of Viral Replication Compartments Isolated from Adenovirus-Infected Cells
Authors: Hidalgo Paloma , Anzures Lourdes , Hernández-Mendoza Armando , Guerrero Adán , Wood Christopher D. , Valdés Margarita , Dobner Thomas , Gonzalez Ramón A. 
Published: January 2016

ABSTRACT

Adenovirus (Ad) replication compartments (RC) are nuclear microenvironments where the viral genome is replicated and a coordinated program of late gene expression is established. These virus-induced nuclear sites seem to behave as central hubs for the regulation of virus-host cell interactions, since proteins that promote efficient viral replication as well as factors that participate in the antiviral response are coopted and concentrated there. To gain further insight into the activities of viral RC, here we report, for the first time, the morphology, composition, and activities of RC isolated from Ad-infected cells. Morphological analyses of isolated RC particles by superresolution microscopy showed that they were indistinguishable from RC within infected cells and that they displayed a dynamic compartmentalization. Furthermore, the RC-containing fractions (RCf) proved to be functional, as they directed
de novo
synthesis of viral DNA and RNA as well as RNA splicing, activities that are associated with RC
in vivo
. A detailed analysis of the production of viral late mRNA from RCf at different times postinfection revealed that viral mRNA splicing occurs in RC and that the synthesis, posttranscriptional processing, and release from RC to the nucleoplasm of individual viral late transcripts are spatiotemporally separate events. The results presented here demonstrate that RCf are a powerful system for detailed study into RC structure, composition, and activities and, as a result, the determination of the molecular mechanisms that induce the formation of these viral sites of adenoviruses and other nuclear-replicating viruses.

IMPORTANCE
RC may represent molecular hubs where many aspects of virus-host cell interaction are controlled. Here, we show by superresolution microscopy that RCf have morphologies similar to those of RC within Ad-infected cells and that they appear to be compartmentalized, as nucleolin and DBP display different localization in the periphery of these viral sites. RCf proved to be functional, as they direct
de novo
synthesis of viral DNA and mRNA, allowing the detailed study of the regulation of viral genome replication and expression. Furthermore, we show that the synthesis and splicing of individual viral late mRNA occurs in RC and that they are subject to different temporal patterns of regulation, from their synthesis to their splicing and release from RC to the nucleoplasm. Hence, RCf represent a novel system to study molecular mechanisms that are orchestrated in viral RC to take control of the infected cell and promote an efficient viral replication cycle.
Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor
Authors: Sarkar Sanjay , Chelvarajan Lakshman , Go Yun Young , Cook Frank , Artiushin Sergey , Mondal Shankar , Anderson Kelsi , Eberth John , Timoney Peter J. , Kalbfleisch Theodore S. , Bailey Ernest , Balasuriya Udeni B. R. 
Published: January 2016

ABSTRACTPrevious studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from <3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 proteinin vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14+monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus.IMPORTANCEOutbreaks of EVA can be a source of significant economic loss for the equine industry from high rates of abortion in pregnant mares, death in young foals, establishment of the carrier state in stallions, and trade restrictions imposed by various countries. Similar to other arteriviruses, EAV primarily targets cells of the monocyte/macrophage lineage, which, when infected, are believed to play a critical role in EVA pathogenesis. To this point, however, the host-specified molecules involved in EAV binding and entry into monocytes/macrophages have not been identified. Identification of the cellular receptors for EAV may provide insights to design antivirals and better prophylactic reagents. In this study, we have demonstrated that EqCXCL16 acts as an EAV entry receptor in EAV-susceptible cells, equine monocytes. These findings represent a significant advance in our understanding of the fundamental mechanisms associated with the entry of EAV into susceptible cells.
ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation
Authors: González-Sanz Rubén , Mata Manuel , Bermejo-Martín Jesús , Álvarez Amparo , Cortijo Julio , Melero José A. , Martínez Isidoro 
Published: January 2016

ABSTRACTHuman respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infectionin vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15−/−) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the moleculein vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus.IMPORTANCEAt present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral rolein vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.