bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge
Authors: Barnum Christopher J , Pace Thaddeus WW , Hu Fang , Neigh Gretchen N , Tansey Malú G 
Published: January 2012

AbstractBackgroundThere is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown.MethodsTo address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation.ResultsAdolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors.ConclusionOur results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.
Using geographical information systems mapping to identify areas presenting high risk for traumatic brain injury
Authors: Colantonio Angela , Moldofsky Byron , Escobar Michael , Vernich Lee , Chipman Mary , McLellan Barry 
Published: January 2012

Abstract
Background
The aim of this study is to show how geographical information systems (GIS) can be used to track and compare hospitalization rates for traumatic brain injury (TBI) over time and across a large geographical area using population based data.

Results & Discussion
Data on TBI hospitalizations, and geographic and demographic variables, came from the Ontario Trauma Registry Minimum Data Set for the fiscal years 1993-1994 and 2001-2002. Various visualization techniques, exploratory data analysis and spatial analysis were employed to map and analyze these data. Both the raw and standardized rates by age/gender of the geographical unit were studied. Data analyses revealed persistent high rates of hospitalization for TBI resulting from any injury mechanism between two time periods in specific geographic locations.

Conclusions
This study shows how geographic information systems can be successfully used to investigate hospitalizaton rates for traumatic brain injury using a range of tools and techniques; findings can be used for local planning of both injury prevention and post discharge services, including rehabilitation.
Factors associated with the occurrence of MRSA CC398 in herds of fattening pigs in Germany
Authors: Alt Katja , Fetsch Alexandra , Schroeter Andreas , Guerra Beatriz , Hammerl Jens A , Hertwig Stefan , Senkov Natalja , Geinets Anna , Mueller-Graf Christine , Braeunig Juliane , Kaesbohrer Annemarie , Appel Bernd , Hensel Andreas , Tenhagen Bernd-Alois 
Published: January 2012

Abstract

Background
The purpose of this study was to investigate the prevalence of MRSA in herds of fattening pigs in different regions of Germany, and to determine factors associated with the occurrence of this pathogen. For this purpose pooled dust samples were collected, and a questionnaire covered information regarding herd characteristics and management practices. Samples were pre-enriched in high-salt medium followed by selective enrichment containing cefoxitin/aztreonam, and culturing. Presumptive colonies were confirmed by multiplex-PCR targeting nuc-, mecA- and 16S rRNA-genes. Isolates were spa- and SCCmec-, and in selected cases, multilocus sequence-typed. Susceptibilities to 13 antimicrobials were determined by broth microdilution. Statistical analysis was carried out using backward stepwise logistic regression to calculate odds ratios with the MRSA test result as the outcome and herd characteristics as categorical covariates.

Results
Overall, 152 of 290 (52%) fattening pig farms tested positive for MRSA. The prevalence in the east, north- and south-west of Germany ranged from 39 to 59%.
t011 (66%) and t034 (23%) were the most commonly identified spa-types, and 85% of isolates carried SCCmec Type V. Identified spa-types were all associated with clonal complex CC398. Susceptibility testing revealed that all isolates were resistant to tetracycline. High resistance rates were also found for sulfamethoxazole/trimethoprim (40%), and quinupristin/dalfopristin (32%). In addition, 83% of strains displayed multidrug resistant (> 3 substance classes) phenotypes.
Logistic regression revealed herd size (large farms OR: 5.4; CI: 2.7-11.2; p < 0.05), and production type (wean-to-finish OR: 4.0; CI: 1.6-10.4; p < 0.05) as risk factors associated with a positive MRSA finding in fattening pig operations.

Conclusions
MRSA CC398 is widely distributed among herds of fattening pigs in Germany. Farm management plays a crucial role in the dissemination of MRSA with herd size, and production type representing potential major indicators.
Amelioration of radiation-induced skin injury by adenovirus-mediated heme oxygenase-1 (HO-1) overexpression in rats
Authors: Zhang Shuyu , Song Chuanjun , Zhou Jundong , Xie Ling , Meng Xingjun , Liu Pengfei , Cao Jianping , Zhang Xueguang , Ding Wei-Qun , Wu Jinchang 
Published: January 2012

Abstract

Objective
Radiation-induced skin injury remains a serious concern for radiation therapy. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant and anti-apoptotic properties. However, the role of HO-1 in radiation-induced skin damage remains unclear. This study aims to elucidate the effects of HO-1 on radiation-induced skin injury in rats.

Methods
A control adenovirus (Ad-EGFP) and a recombinant adenovirus (Ad-HO1-EGFP) were constructed. Rats were irradiated to the buttock skin with a single dose of 45 Gy followed by a subcutaneous injection of PBS, 5 × 109 genomic copies of Ad-EGFP or Ad-HO1-EGFP (n = 8). After treatment, the skin MDA concentration, SOD activity and apoptosis were measured. The expression of antioxidant and pro-apoptotic genes was determined by RT-PCR and real-time PCR. Skin reactions were measured at regular intervals using the semi-quantitative skin injury score.

Results
Subcutaneous injection of Ad-HO1-EGFP infected both epidermal and dermal cells and could spread to the surrounding regions. Radiation exposure upregulated the transcription of the antioxidant enzyme genes, including SOD-1, GPx2 and endogenous HO-1. HO-1 overexpression decreased lipid peroxidation and inhibited the induction of ROS scavenging proteins. Moreover, HO-1 exerted an anti-apoptotic effect by suppressing FAS and FASL expression. Subcutaneous injection of Ad-HO1-EGFP demonstrated significant improvement in radiation-induced skin injury.

Conclusions
The present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury.
A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements
Authors: Enroth Stefan , Andersson Claes R , Andersson Robin , Wadelius Claes , Gustafsson Mats G , Komorowski Jan 
Published: January 2012

Abstract

Background
High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e.g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a pre-processing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns.

Results
We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background.

Conclusions
The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise.
Spectral Karyotyping for identification of constitutional chromosomal abnormalities at a national reference laboratory
Authors: Anguiano Arturo , Wang Boris T , Wang Shirong R , Boyar Fatih Z , Mahon Loretta W , El Naggar Mohamed M , Kohn Peter H , Haddadin Mary H , Sulcova Vladimira , Sbeiti Adam H , Ayad Mervat S , White Beverly J , Strom Charles M 
Published: January 2012

Abstract
Spectral karyotyping is a diagnostic tool that allows visualization of chromosomes in different colors using the FISH technology and a spectral imaging system. To assess the value of spectral karyotyping analysis for identifying constitutional supernumerary marker chromosomes or derivative chromosomes at a national reference laboratory, we reviewed the results of 179 consecutive clinical samples (31 prenatal and 148 postnatal) submitted for spectral karyotyping. Over 90% of the cases were requested to identify either small supernumerary marker chromosomes (sSMCs) or chromosomal exchange material detected by G-banded chromosome analysis. We also reviewed clinical indications of those cases with marker chromosomes in which chromosomal origin was identified by spectral karyotyping. Our results showed that spectral karyotyping identified the chromosomal origin of marker chromosomes or the source of derivative chromosomal material in 158 (88%) of the 179 clinical cases; the identification rate was slightly higher for postnatal (89%) compared to prenatal (84%) cases. Cases in which the origin could not be identified had either a small marker chromosome present at a very low level of mosaicism (< 10%), or contained very little euchromatic material. Supplemental FISH analysis confirmed the spectral karyotyping results in all 158 cases. Clinical indications for prenatal cases were mainly for marker identification after amniocentesis. For postnatal cases, the primary indications were developmental delay and multiple congenital anomalies (MCA). The most frequently encountered markers were of chromosome 15 origin for satellited chromosomes, and chromosomes 2 and 16 for non-satellited chromosomes. We were able to obtain pertinent clinical information for 47% (41/88) of cases with an identified abnormal chromosome. We conclude that spectral karyotyping is sufficiently reliable for use and provides a valuable diagnostic tool for establishing the origin of supernumerary marker chromosomes or derivative chromosomal material that cannot be identified with standard cytogenetic techniques.
Molecular profiling of patient-derived breast cancer xenografts
Authors: Reyal Fabien , Guyader Charlotte , Decraene Charles , Lucchesi Carlo , Auger Nathalie , Assayag Franck , De Plater Ludmilla , Gentien David , Poupon Marie-France , Cottu Paul , De Cremoux Patricia , Gestraud Pierre , Vincent-Salomon Anne , Fontaine Jean-Jacques , Roman-Roman Sergio , Delattre Olivier , Decaudin Didier , Marangoni Elisabetta 
Published: January 2012

Abstract
Introduction
Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors.

Methods
Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays.

Results
Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time.

Conclusions
This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents.
Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review
Authors: Xing Katharine , Murthy Srinivas , Liles W Conrad , Singh Jeffrey M 
Published: January 2012

Abstract
Introduction
A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.

Methods
The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.

Results
Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.

Conclusions
Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.
Multicenter Analysis of Quality Indicators for Children Treated in the Emergency Department for Asthma
Authors: Sills Marion R. , Ginde Adit A. , Clark Sunday , Camargo Carlos A. 
Published: January 2012

OBJECTIVE:
To test the hypothesis that an association exists between process and outcome measures of the quality of acute asthma care provided to children in the emergency department.

METHODS:
Investigators at 14 US sites prospectively enrolled consecutive children 2 to 17 years of age presenting to the emergency department with acute asthma. In models adjusted for variables commonly associated with the quality of acute asthma care, we measured the association between 7 measures of concordance with national asthma guideline-recommended processes and 2 outcomes. Specifically, we modeled the association between 5 receipt/nonreceipt process measures and successful discharge and the association between 2 timeliness measures and admission.

RESULTS:
In this cohort of 1426 patients, 62% were discharged without relapse or ongoing symptoms (successful discharge), 15% were discharged with relapse or ongoing symptoms, and 24% were admitted. The composite score for receipt of all 5 receipt/nonreceipt process measures was 84%, and for timeliness measures, 57% receive a timely corticosteroid and 92% a timely β-agonist. Our adjusted models showed no association between process and outcome measures, with 1 exception: timely β-agonist administration was associated with admission, likely reflecting confounding by severity rather than a true process-outcome association.

CONCLUSIONS:
We found no clinically significant association between process and outcome quality measures in the delivery of asthma-related care to children in a multicenter study. Although the quality of emergency department care does not predict successful discharge, other factors, such as outpatient care, may better predict outcomes.
Lead Poisoning in United States-Bound Refugee Children: Thailand-Burma Border, 2009
Authors: Mitchell Tarissa , Jentes Emily , Ortega Luis , Scalia Sucosky Marissa , Jefferies Taran , Bajcevic Predrag , Parr Valentina , Jones Warren , Brown Mary Jean , Painter John 
Published: January 2012

BACKGROUND:
Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described.

METHODS:
Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary &lt;3.3 µg/dL) blood lead levels participated in a case-control study.

RESULTS:
Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged &lt;2 years had the highest prevalence (14.5%). Among children aged &lt;2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin &lt;10 g/dL, exposure to car batteries, and taking traditional medicines.

CONCLUSIONS:
The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children &lt;2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.
Pertussis Pseudo-outbreak Linked to Specimens Contaminated by Bordetella pertussis DNA From Clinic Surfaces
Authors: Mandal Sema , Tatti Kathleen M. , Woods-Stout Denise , Cassiday Pamela K. , Faulkner Amanda E. , Griffith Matthew M. , Jackson Michael L. , Pawloski Lucia C. , Wagner Bari , Barnes Meghan , Cohn Amanda C. , Gershman Ken A. , Messonnier Nancy E. , Clark Thomas A. , Tondella Maria-Lucia C. , Martin Stacey W. 
Published: January 2012

BACKGROUND AND OBJECTIVES:
We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions.

METHODS:
We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators.

RESULTS:
Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P &lt; .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P &lt; .01), and a greater proportion of PCR-positive results (34% vs 6%; P &lt; .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs.

CONCLUSIONS:
A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.